← Product Code MNQ · P240024

# Genio® System 2.1 (P240024)

_Nyxoah S.A. · MNQ · Aug 8, 2025 · Anesthesiology · APPR_

**Canonical URL:** https://fda.innolitics.com/device/P240024

## Device Facts

- **Applicant:** Nyxoah S.A.
- **Product Code:** MNQ
- **Decision Date:** Aug 8, 2025
- **Decision:** APPR
- **Device Class:** Class 3
- **Review Panel:** Anesthesiology
- **Attributes:** Therapeutic

## Indications for Use

The Genio® System 2.1 is indicated for use in the treatment of moderate to severe Obstructive Sleep Apnea (OSA) (apnea-hypopnea index [AHI] of greater than or equal to 15 and less than or equal to 65). The Genio® System 2.1 is intended for adult patients 22 years of age and older who have been confirmed to fail, cannot tolerate or are ineligible to be treated with current standard of care treatments including lifestyle modifications, positive airway pressure (PAP) treatments (such as continuous positive airway pressure [CPAP] or bi-level positive airway pressure [BiPAP] machines), oral appliances (such as mandibular advancement devices), and pharmacotherapy (such as tirzepatide). PAP failure is defined as an inability to eliminate OSA (residual AHI of greater than 15 despite PAP usage), and PAP intolerance is defined as: 1. Inability to use PAP (at least 5 nights per week of usage; usage defined as greater than 4 hours of use per night), or 2. Unwillingness to use PAP (PAP therapy initiated and subsequently discontinued by choice).

## Device Story

Genio® System 2.1 is a hypoglossal nerve stimulator for moderate-to-severe OSA. System includes an Implantable Stimulator (IS) placed under the chin to stimulate hypoglossal nerve branches bilaterally; an external Activation Chip (AC) attached to a disposable adhesive patch; and a Charging Unit. The IS contains no battery or software; it receives energy pulses wirelessly from the AC. Stimulation causes tongue muscle contraction, maintaining airway patency during sleep. Nyxoah field personnel program stimulation parameters via a Sleep Lab Application on a mini-computer. Patients use an optional Smartphone App to pause/resume therapy and adjust amplitude within physician-set limits. The device is used at home by the patient. Output is electrical stimulation of the hypoglossal nerve, which reduces airway obstruction, improves sleep quality, and reduces snoring. Benefits include improved AHI/ODI, reduced hypoxemic burden, and high patient satisfaction.

## Clinical Evidence

Pivotal DREAM study (IDE G190068): prospective, multi-center, single-arm study (N=115 implanted). Co-primary endpoints: AHI4 responder rate (≥50% reduction and residual AHI4 <20) and ODI4 responder rate (≥25% reduction) at 12 months. Results: AHI4 responder rate 66.4% (FAS, N=110), ODI4 responder rate 74.5%. All 6 secondary endpoints (SNORE-25, hypoxemic burden, ODI4, FOSQ-10, ESS, AHI4) met. Safety: 6.1% device-related and 5.2% procedure-related SAE rate through 12 months. Bench testing and animal studies supported safety/performance.

## Technological Characteristics

Implantable Stimulator (IS) Model #2954: ceramic housing, antenna, electrical circuit, paddle electrodes. Energy source: RF energy from external Activation Chip. Connectivity: Bluetooth Low Energy (BLE) for AC-to-Smartphone/Repeater communication. Sterilization: Ethylene Oxide (EO). Software: Sleep Lab Application (configuration), Smartphone Application (patient control). MR Conditional (1.5T/3T).

## Submission Summary (Full Text)

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SUMMARY OF SAFETY AND EFFECTIVENESS DATA (SSED)

I. GENERAL INFORMATION

Device Generic Name: Genio® System for Obstructive Sleep Apnea (OSA)
Device Trade Name: Genio® System 2.1
Device Product Code: MNQ
Applicant's Name and Address: Nyxoah Inc.
251 Little Falls Drive
Wilmington, DE 19808
Date of Panel Recommendation: None
Premarket Approval Application (PMA) Number: P240024
Date of FDA Notice of Approval: 08/08/25

II. INDICATIONS FOR USE

The Genio® System 2.1 is indicated for use in the treatment of moderate to severe Obstructive Sleep Apnea (OSA) (apnea-hypopnea index [AHI] of greater than or equal to 15 and less than or equal to 65). The Genio® System 2.1 is intended for adult patients 22 years of age and older who have been confirmed to fail, cannot tolerate or are ineligible to be treated with current standard of care treatments including lifestyle modifications, positive airway pressure (PAP) treatments (such as continuous positive airway pressure [CPAP] or bi-level positive airway pressure [BiPAP] machines), oral appliances (such as mandibular advancement devices), and pharmacotherapy (such as tirzepatide).

PAP failure is defined as an inability to eliminate OSA (residual AHI of greater than 15 despite PAP usage), and PAP intolerance is defined as:

1. Inability to use PAP (at least 5 nights per week of usage; usage defined as greater than 4 hours of use per night), or
2. Unwillingness to use PAP (PAP therapy initiated and subsequently discontinued by choice).

III. CONTRAINDICATIONS

The Genio® System 2.1 is contraindicated for:

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- Patients with combined central and mixed apnea-hypopnea index greater than or equal to 25% of the total AHI.
- Patients with any functional or structural problem, medical illness or condition that would prevent or interfere with implantation, activation or continued use of the Genio therapy.
- Patients with an implantable device which may be susceptible to unintended interaction with the Genio® System. Consult the device manufacturer to assess the possibility of interaction.
- Women who are pregnant, planning to become pregnant or breastfeeding.
- Any condition or procedure that has compromised neurological control of the upper airway.

## IV. WARNINGS AND PRECAUTIONS

The warnings and precautions can be found in the Genio® System 2.1 labeling.

## V. DEVICE DESCRIPTION

The Genio® System 2.1 is a hypoglossal nerve stimulator intended for the treatment of moderate to severe Obstructive Sleep Apnea (OSA). It consists of an Implantable Stimulator (IS) designed to stimulate the hypoglossal nerve (HGN) terminal branches bilaterally (i.e., both the left and the right). The IS does not include a battery or software but receives energy pulses transmitted by either the External Stimulator (ES) during the implantation procedure or the Activation Chip (AC) during therapy which is attached to an adhesive Disposable Patch (DP) and placed on the patient's skin under the chin. The Genio waveform received by the IS is a rectified square wave that allows for passive discharge to achieve charge balanced stimulation pulses which are delivered to the HGN. Stimulation of the HGN causes specific tongue muscles to contract resulting in the forward movement of the tongue which in turn maintains an open airway during the patient's sleep.

During awake or sleep lab titration, the stimulation parameters transmitted by the AC to the IS are programmed using the Sleep Lab Application software which is run on an off-the-shelf mini-computer (Repeater). Once an optimal stimulation amplitude range has been programmed for the AC, a Smartphone Application available on both Android and iOS devices can be used by the patient to pause and resume treatment as well as adjust the stimulation level within a pre-defined safe range. The range is set by the Nyxoah field personnel (Registered Polysomnography Technologist) under the directions provided by the physician. The AC is charged daily using a Charging Unit (CU). The Genio® System 2.1 components for patient use are shown in Figure 1 below.

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![img-0.jpeg](img-0.jpeg)
Figure 1. Genio® System 2.1 Components for patient use

A description of the implanted and external components of the Genio® System 2.1 are provided below. Additionally, a summary of the technical specifications for each of the physical Genio® System 2.1 components (i.e., components that are not software) has been provided in Table 1.

Table 1. Technical Specifications of the Genio® System 2.1 Components

|  Component | Dimensions | Weight | Shelf-life | Service Life  |
| --- | --- | --- | --- | --- |
|  Implantable Stimulator Model #2954 | L=27.3mm W=20.7mm H=4.4mm | 6.18g | 2 years | At least 12 years  |
|  Surgical Template | L=27.3mm W=20.7mm H=4.4mm | 3.09g | 2 years | N/A – single use disposable device  |
|  External Stimulator | L=115.15mm W=23.5mm H=33.8mm | 28.90g | 1 year | N/A – single use disposable device  |
|  Disposable Patch (liner included) | L=101mm W=71.7mm H=6.61mm | 3.25g | Sealed bag: Maximum 16 months Opened bag: 15 days | N/A – single use disposable device  |

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|  Activation Chip Model #2364 | Ø = 31.40mm H=20.55mm | 12.18g | 1 year | At least 12 months  |
| --- | --- | --- | --- | --- |
|  Charging Unit Model #2238 | L=110mm W=50mm H=17mm | 61.69g | 1 year | At least 12 months  |

# Implantable Stimulator (IS) Model #2954

The IS Model #2954 is a single-use, sterile, small saddle-shaped implant that delivers stimulation to both HGN branches (i.e. left and right). The body of the IS consists of an energy receiving antenna and an electrical circuit both encapsulated in a ceramic housing, and two lateral legs with a pair of paddle electrodes. It is powered and controlled by either the AC or ES externally. The IS does not include a battery or a microcontroller or software. The IS is implanted in a single incision surgical procedure under the chin and placed over the genioglossus muscle with its paddle electrodes facing both left and right HGN branches. The device is sutured in place to the genioglossus muscle using the four IS leg suturing pads. The electrodes conduct stimulation energy to the HGN, resulting in contraction of the tongue muscles. This process can help maintain an open airway and normal breathing during sleep. The IS is the only implantable component of the Genio® System 2.1. An illustration of the anatomical location of the IS once implanted is shown in Figure 2 below.

![img-1.jpeg](img-1.jpeg)
Figure 2. Illustration of Genio® System 2.1 Anatomical Location including Suturing Points

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The Genio® Implantable Stimulator Model #2954 (Figure 3) is a Magnetic Resonance (MR) Conditional device which means that the implant is safe in the MR environment within certain conditions.

![img-2.jpeg](img-2.jpeg)
Figure 3: Implantable Stimulator (IS) Model #2954

Packaged with the IS Model #2954 is the Surgical Template (ST) (Figure 4). The ST is a single use, sterile accessory which can be optionally used for preparation of the implantation site.

![img-3.jpeg](img-3.jpeg)
Figure 4: Surgical Template

## External Stimulator (ES)

The ES (Figure 5) is a single-use, sterile accessory that allows the surgeon to activate the IS and verify the functionality of the implant during the surgical procedure. The ES contains a power button with an LED indicator, a pre-charged battery and a retractable scaling mechanism to control the stimulation intensity delivered to the implant.

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![img-4.jpeg](img-4.jpeg)
Figure 5. External Stimulator

# Disposable Patch (DP)

The DP (Figure 6) is a single-use adhesive patch placed on the skin under the chin each night by the user. The Activation Chip is snapped onto the DP using a button connector. Once snapped together, stimulation energy can be transmitted wirelessly to the IS. The DP is comprised of a flexible Printed Circuit Board (PCB) (the antenna) and an adhesive patch.

![img-5.jpeg](img-5.jpeg)
Figure 6. Disposable Patch

# Activation Chip (AC) Model #2364

The AC (Figure 7) is the power source for the IS. The AC contains a rechargeable battery, electronics for Bluetooth communication and electromagnetic power transmission, and a microprocessor that stores the user-specific stimulation parameters. Nyxoah field personnel (Registered Polysomnography Technologist) program the AC stimulation parameters specific for each user to provide optimal therapy under the guidance of the Health Care Provider (HCP). The AC must be connected to the DP and placed on the chin each night for stimulation to be delivered, and the battery must be recharged daily.

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![img-6.jpeg](img-6.jpeg)
Figure 7. Activation Chip Model #2364

# Charging Unit (CU) Model # 2238

The CU (Figure 8) and its power adapter are used to recharge the AC battery during the day in order to be ready for use the following night. The CU is comprised of a docking area to plug the AC in, a power LED indicator and a micro-USB port to connect to the power adapter.

![img-7.jpeg](img-7.jpeg)
Figure 8. Charging Unit Model # 2238

# Sleep Lab Application

The Sleep Lab Application (Figure 9) is used by Nyxoah field personnel to configure the AC stimulation parameters. This remote application runs on a small mini-computer (Repeater) and uses Bluetooth low energy (BLE) protocol to enable the operator to configure/customize the AC stimulation parameters. Once the AC is connected to a DP, the Sleep Lab App can be used to perform AC check-ups, read usage data stored in the AC and program/adjust the stimulation parameters.

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![img-8.jpeg](img-8.jpeg)
Figure 9. Sleep Lab Application

# Smartphone Application (optional)

The AC can be controlled by an optional Smartphone Application (Figure 10), designed to operate on both Android and iOS devices which allows the patient to pause and resume stimulation and to increase/decrease the treatment amplitude within a preconfigured range. The Smartphone App uses BLE protocol to communicate with a paired AC.

![img-9.jpeg](img-9.jpeg)
Figure 10. Smartphone Application

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# Stimulation Parameters

The stimulation parameters are controlled by the AC and configured in the sleep lab using the Sleep Lab App. These parameters include pulse amplitude, frequency, duration as well as stimulation train parameters such as train length (on time) and train interval (off time). The pre-defined range for the stimulation parameters is configured by field personnel (Registered Polysomnography Technologists) in accordance with direction provided by the sleep physician. Using the optional Smartphone App, the patient also has the ability to fine tune the amplitude, within a pre-defined limit. Table 2 below lists the configured stimulation parameters values. All parameters can only be modified by the field personnel except for amplitude which can be fine-tuned by the patient using the optional Smartphone App.

Table 2. Stimulation Parameters Ranges, steps and default values

|  Treatment Parameter | Description | Available Range (step) | Default Setting  |
| --- | --- | --- | --- |
|  Pulse Length | Duration of one stimulation pulse | 50-250 μsec (10μsec) | 100 μsec  |
|  Pulse Frequency | Pulse repetition rate within stimulation train | 30-50 Hz (5Hz) | 30 Hz  |
|  Train Length | Duration of stimulation train | 0.2-5sec (0.1sec) | 1 sec  |
|  Train Interval | Duration of pause between stimulation trains | 0.2-5sec (0.1sec) | 4 sec  |
|  Treatment Amplitude | Stimulation amplitude | 1-100 % (1%) | 1%  |
|  Lowest Amplitude Limit | Stimulation amplitude bottom limit for Smartphone application | 1-100 % (1%) | 1%  |
|  Highest Amplitude Limit | Stimulation amplitude top limit for Smartphone application | 1-100 % (1%) | 1%  |
|  Delay time | Time between the connection of the AC-DP and the start of the stimulation therapy | 5-60 min (5min) | 30 min  |
|  Ramp Up duration | Time for stimulation amplitude ramp up within train (linear distribution). | 0 -1000 msec (50msec) | 0 - Not active  |
|  Hold Time Duration | Duration time after reaching train amplitude target prior to step-down execution | 0 - 500 msec (50msec) | 0 - Not active  |
|  Step down Target amplitude | Stimulation amplitude step reduction within a pulse | 1 - 100% (1%) | 0 - Not active  |
|  Ramp at stimulation Onset | Time for stimulation amplitude ramp up between trains (linear distribution) during the treatment initiation. | 0-30 min (5min) | 0 - Not active  |

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The stimulation parameters described in Table 2 above are illustrated in Figure 11 through Figure 13 below. These figures provide a visual representation of the IS stimulation pulses delivered to the HGN when triggered by the radiofrequency (RF) energy sent from the AC. Figure 11 illustrates the train length, train interval, pulse amplitude, pulse frequency and pulse duration stimulation parameters. The amplitude ramp up within each train setting is depicted in Figure 12 while the stimulation ramp up at therapy initiation setting parameters are shown in Figure  $13_{2}$

![img-10.jpeg](img-10.jpeg)
Figure 11. Illustration of Genio® System 2.1 stimulation parameters (l = train length, i = train interval, a = treatment amplitude, r = pulse frequency, p = pulse duration, d = delay time)

![img-11.jpeg](img-11.jpeg)
Figure 12. Amplitude ramp up within each train pulse setting parameters (B = ramp up duration, C = hold time duration, D = step down target amplitude)

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![img-12.jpeg](img-12.jpeg)
Figure 13. Stimulation ramp-up at the therapy initiation setting parameters (a = treatment amplitude, d = delay time, R = ramp at stimulation onset)

# VI. ALTERNATIVE PRACTICES AND PROCEDURES

There are several other alternatives for the correction of obstructive sleep apnea (OSA), including lifestyle changes (e.g., weight loss and positional therapy), PAP (Positive airway pressure), oral appliances (mandibular advancement device), anatomical surgery, and pharmacotherapy (e.g., tirzepatide).

Each alternative has its own advantages and disadvantages. A patient should thoroughly discuss the risks and benefits of treatment alternatives with his/her physician to select the treatment method that best meets their needs.

# VII. MARKETING HISTORY

The original Genio® System received CE mark approval on 12 March 2019 under the Active Implantable Medical Devices Directive (AIMDD), while the Genio® System 2.1 was subsequently approved under the Medical Device Regulation (MDR) on 15 July 2022. Both devices have been successfully marketed in the European Union since their respective approvals, with a comparison provided in Table 3. There have been no reports of the Genio® System 2.1 being withdrawn from the European Union market."

The Genio® System 2.1 has not been previously marketed in the United States. Additionally, the Genio® Implantable Stimulator Model #2954 has not received prior marketing approval in any jurisdiction worldwide.

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Table 3. Genio® System Comparison

|  System Component | Genio® System (CE Mark under AIMDD) | Genio® System 2.1 (CE Mark under MDR) | Genio® System 2.1 (PMA P240024)  |
| --- | --- | --- | --- |
|  Implantable Stimulator (IS) | Genio® Implantable Stimulator | Genio® Implantable Stimulator | Genio® Implantable Stimulator Model #2954  |
|  External Stimulator (ES) | Genio® External Stimulator | Genio® External Stimulator | Genio® External Stimulator  |
|  Disposable Patch (DP) | Genio® Disposable Patch | Genio® Disposable Patch | Genio® Disposable Patch  |
|  Activation Chip (AC) | Genio® Activation Chip Model #2218 | Genio® Activation Chip Model #2364 | Genio® Activation Chip Model #2364  |
|  Charging Unit (CU) | Genio® Charging Unit Model # 2219 | Genio® Charging Unit Model #2238 | Genio® Charging Unit Model #2238  |
|  Sleep Lab Applications | Genio® Sleep Lab Application | Genio® Sleep Lab Application (updated) | Genio® Sleep Lab Application (updated)  |
|  Bluetooth Snap Device (BTSD) | Genio® Bluetooth Snap Device | N/A (obsoleted) | N/A  |
|  Smartphone Application (optional) | N/A | Genio® Smartphone Application | Genio® Smartphone Application  |

# VIII. POTENTIAL ADVERSE EFFECTS OF THE DEVICE ON HEALTH

Below is a list of the potential adverse effects (e.g., complications) associated with the use of the device.

- Temporary local skin irritation
- Impaired or painful swallowing due to the device
- Discomfort or pain due to electrical stimulation
- Mouth blisters (due to tongue rubbing against teeth during stimulation)
- Mild to moderate pain, swelling, stiffness or tenderness at the implant site or with the use of the device
- Mild tongue abrasion
- Abnormal scarring
- Tongue fasciculations (twitching of tongue)
- Dry mouth
- Temporary tongue muscle weakness or soreness
- Temporary usability or functionality issues with an external device leading to temporary delay of treatment
- Permanent usability or functionality issues with an external device leading to no therapy
- Usability or functionality issues with the implanted device

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- Increased or continued snoring
- Headache or dizziness
- Fatigue or sleep disturbances, while acclimating to stimulation
- Change in salivary flow
- Clinically significant implant migration (device moving from implanted location and potential partial or complete expulsion of the device from its intended place)
- Impaired sense of taste or metallic taste
- Increased acid reflux
- Increased upper airway secretions
- Paresthesia (sensation of tickling or itching)
- Pain or irritation in the throat or nasal passage
- Allergic and/or rejection response to the implanted device
- Damage to tissue (nerves, blood vessels or muscles) in contact with the implant or in the vicinity of the implant
- Damage to tissue in contact with external devices
- Persistent pain at the implant site
- Impaired or painful speaking due to the device
- Risks related to additional surgery and any unstudied potential effect
- Infection
- Hematoma
- Bleeding
- Cellulitis at surgical site
- Presence of fibrosis making the removal of the Genio® Implantable Stimulator Model #2954 difficult without damaging the surrounding structures

For the specific adverse events that occurred in the clinical study, please see Section X below.

## IX. SUMMARY OF NONCLINICAL STUDIES

Nonclinical testing for the Genio® System 2.1 encompassed a range of evaluations, including bench testing of the device, software and cybersecurity assessments, biocompatibility, sterilization, packaging, shelf-life, MRI safety, electrical safety, electromagnetic compatibility, mechanical/structural durability, human factors, and animal studies. These tests were conducted in accordance with design specifications, as well as relevant standards and guidance documents. A summary of the results for each test is provided below.

## A. Biocompatibility

A biocompatibility evaluation was conducted for the Genio® System 2.1 devices in accordance with ISO 10993-1 and its associated standards. The evaluation concluded that none of the Genio® System 2.1 devices contained material which poses a biocompatibility risk to the user. A summary of the Genio® System 2.1 biocompatibility evaluation is provided in Table 4.

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Table 4. Summary of the Genio® System 2.1 Biocompatibility Evaluation

|  Test | Device | Purpose | Result  |
| --- | --- | --- | --- |
|  Cytotoxicity
ISO 10993-5:2009 | Implantable Stimulator Model #2954 | Evaluate the Genio® System 2.1 for potential cytotoxic effects. | Pass; non-cytotoxic  |
|   |  Surgical Template  |   |   |
|   |  External Stimulator  |   |   |
|   |  Disposable Patch  |   |   |
|   |  Activation Chip Model #2364  |   |   |
|   |  Charging Unit Model #2238  |   |   |
|  Sensitization
ISO 10993-10:2010 | Implantable Stimulator Model #2954 | Evaluate the Genio® System 2.1 for the potential to cause delayed dermal contact sensitization. | Pass; non-sensitizer  |
|   |  Surgical Template  |   |   |
|   |  External Stimulator  |   |   |
|   |  Disposable Patch  |   |   |
|   |  Activation Chip Model #2364  |   |   |
|   |  Charging Unit Model #2238  |   |   |
|  Irritation/Intracutaneous Reactivity
ISO 10993-10:2021 | Implantable Stimulator Model #2954 | Evaluate the Genio® System 2.1 for the potential to cause local dermal irritation. | Pass; non-irritating

Note: There were no gaps between the 2010 and 2021 version of the standard which would necessitate additional testing for these components.  |
|   |  Surgical Template  |   |   |
|  Irritation/Intracutaneous Reactivity
ISO 10993-10:2010 | External Stimulator  |   |   |
|   |  Disposable Patch  |   |   |
|   |  Activation Chip Model #2364  |   |   |
|   |  Charging Unit Model #2238  |   |   |

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|  Test | Device | Purpose | Result  |
| --- | --- | --- | --- |
|  Implantation/Subchronic Toxicity
ISO 10993-11:2017
ISO 10993-6:2016 | Implantable Stimulator Model #2954 | Assess the local and systemic effects of the IS Model #2954 following 13 weeks intramuscular implantation. | Pass; no microscopic evidence of cytotoxicity was observed. Macroscopic gross tissue examination of the implant sites revealed no abnormalities for the test article. The test article showed no local or systemic signs of toxicity when implanted in rabbits for up to 90 days. Additionally, no clinically significant differences were noted in hematology, serum chemistry, or coagulation parameters. No systemic toxic effects were observed.  |
|  Genotoxicity
ISO 10993-3:2014 | Implantable Stimulator Model #2954 | Evaluate the IS Model #2954 for mutagenic potential and carcinogenic hazards. | Pass; non-genotoxic and non-mutagenic  |
|  Material-Mediated Pyrogenicity
ISO 10993-11:2017 | Implantable Stimulator Model #2954 | Determine whether the IS Model #2954, External Stimulator and Surgical Template induce a pyrogenic response. | Pass; non-pyrogenic  |
|   |  External Stimulator  |   |   |
|   |  Surgical Template  |   |   |
|  Acute Systemic Toxicity
ISO 10993-11:2017 | Implantable Stimulator Model #2954 | Determine whether the IS Model #2954, External Stimulator and Surgical Template induce systemic toxicity from an acute exposure. | Pass; systemically non-toxic  |
|   |  External Stimulator  |   |   |
|   |  Surgical Template  |   |   |
|  Chemical Characterization
ISO 10993-18:2020 | Implantable Stimulator Model #2954 | Chemical characterization of volatile organic compounds, semi-volatile organic compounds, non-volatile organic | The risk assessment of extractables suggests that the use of the IS Model #2954 or Surgical Template will not present a  |
|   |  Surgical Template  |   |   |

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|  Test | Device | Purpose | Result  |
| --- | --- | --- | --- |
|  Toxicological Evaluation ISO 10993-17:2023 | Implantable Stimulator Model #2954 | compounds, and toxicological risk assessment were performed to evaluate the endpoints of chronic systemic toxicity and carcinogenicity for IS Model #2954 and Surgical Template. | significant toxicological or biocompatibility risk.  |
|  Toxicological Evaluation ISO 10993-17:2002 | Surgical Template  |   |   |

# B. Bench Testing

Bench testing of the Genio® System 2.1 devices were conducted to confirm compliance with applicable design requirements and standards. A summary of the test, purpose, acceptance criteria and results for each bench test are provided in Table 5 through Table 10.

Table 5. Summary of Bench Testing Performed on the IS Model #2954

|  Test | Test Purpose | Acceptance Criteria | Result  |
| --- | --- | --- | --- |
|  Hermeticity Test | Verify that the encapsulation hermeticity adequately protects the electrical circuit from ingress of fluids which may impact the performance or functionality during the device lifetime and that the encapsulation provides protection from release of internal material to the physiological environment | The maximum allowed leak rate of the IS Model #2954 shall be less than: 5 × 10-9pa×m3/s | Pass  |
|  Residual Gas Analysis (RGA) Test | Show that the process used to evacuate dry air (Bake-Out and Helium Backfilling) prior to making the hermetic seal of the implant is effective | The moisture content of the implant shall be ≤ 5,000ppmv (0.5% v/V) | Pass  |
|  Dimensions and Weight Test | Ensure compliance with dimensional design requirements | The fully assembled IS shall meet predetermined physical dimensions and weight: - Length: 27mm +0mm/-0.5mm - Width: ≤ 23mm - Height (thickness): ≤ 5.0mm- - Weight ≤ 10g | Pass  |

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|  Test | Test Purpose | Acceptance Criteria | Result  |
| --- | --- | --- | --- |
|  Fatigue Test | Ensure that the functionality of the IS Model #2954 would not be affected by the mechanical and environmental conditions which would be encountered inside the body during the device's lifetime (12 years) | The tested units shall meet the visual and electrical acceptance criteria after at least 162 million mechanical cycles in the test apparatus | Pass  |
|  Shock and Vibration Test | Show that the assembly can withstand mechanical stresses without degradation to its functionality or performance as required by ISO 14708-1:2014 §23.2 and §23.7 | The IS Model #2954 shall be functional after exposure to mechanical forces and shocks, and meet both visual and electrical functional inspections | Pass  |
|  High/Low Pressure Test | Ensure that the implant, when packed in its final packaging, remained fully functional and safe to use when exposed to high and low pressures per ISO 14708-1:2014 §25.1 | The tested units shall be functional after exposure to high [150 ± 7.5 kPa] and low [70 ± 3.5 kPa] pressure changes -by meeting visual and electrical functional inspection criteria | Pass  |
|  Temperature Changes Test | Ensure that the device remains functional and safe for use when exposed to temperatures which may be encountered during storage or transportation per ISO 14708-1:2014 §26.2 | After exposure to high [55°C ± 2°C] and low [-10°C ± 3°C] temperatures and temperature cycling, the IS Model #2954 shall meet visual and electrical functional inspection criteria | Pass  |
|  Mechanical Strength Test | Confirm that the mechanical integrity of the implant is retained after it is subjected to the forces and/or displacements which may be inflicted on the device by the Genioglossus muscle or during handles of the device | The IS Model #2954 functionality shall not be affected by mechanical forces; all electrical parameters measurements shall meet specifications and no visual changes shall occur as a result of exposure to mechanical forces | Pass  |
|  Water Ingress Test | Ensure that no fluid ingress occurs in order to guarantee safe use and proper functioning of the implant | The implant shall operate and perform as intended, i.e. - shall meet predefined electrical performance criteria. The implant shall not show visible change in appearance or damage to the silicone coverage or electrodes. | Pass  |

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|  Test | Test Purpose | Acceptance Criteria | Result  |
| --- | --- | --- | --- |
|   |  | The implant shall pass RGA test and moisture content shall be ≤ 5000ppmv (0.5%v/v) after the test. |   |
|  Test | Test Purpose | Acceptance Criteria* | Result  |
| --- | --- | --- | --- |
|  Finite Element Analysis | To determine forces acting on each individual suture under small static displacement of implant (< 2.5 mm) | Anterior suture
• < 0.24 N in Anteroposterior direction
• < 0.11 N in Craniocaudal direction
Posterior suture
• <0.2 N in Anteroposterior direction
• <0.22 N in Craniocaudal direction | Pass  |
|  Tensile Tests-Implant fixed on a rigid testing fixture | To determine forces exerted on implant’s shoulders under large displacement of implant (up to 10 mm) | < 6 N in Anteroposterior direction
< 14 N in Craniocaudal direction | Pass  |
|  Tensile Tests (in-vitro) - Implant sutured on animal tissue | To determine forces exerted on implant’s shoulders under large displacement of implant (up to 20 mm) | Intact system
• < 2.7 N in Anteroposterior direction
• < 1.6 N in Craniocaudal direction
System with one compromised suture
• <1.3 N in Anteroposterior direction
• <0.65 N in Craniocaudal direction | Pass  |
|   |  To determine the required displacement of implant to cause suture pull-out | One suture pull-out
• < 37 mm in Anteroposterior direction
• < 53 mm in Craniocaudal direction
Two sutures pull-out
• <48 mm in Anteroposterior direction
• <63 mm in Craniocaudal direction | Pass  |

* Acceptance criteria were established based on test results of a previous version of IS.

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Table 6. Summary of Bench Testing Performed on the External Stimulator (ES)

|  Test | Test Purpose | Acceptance Criteria | Result  |
| --- | --- | --- | --- |
|  Retraction Mechanism Test | Ensure that the ES retractor movement's protection prevents unintended movement of the retractor as a result of applied force | The ES retractor protection mechanism shall prevent movement while pressed up to a force of 2Kgf (~20N) | Pass  |
|  Power Button Durability Test | Demonstrate that the ON/OFF button is able to withstand the forces applied by the surgeon during the implantation procedure without any failure to device performance | The ES functionality shall not be affected by mechanical forces, i.e. – the ES shall meet predefined electrical performance criteria. | Pass  |
|  Operational Battery Lifetime Test | Show there is no performance degradation of the device during low battery conditions and that the battery lifetime meets the design requirements | The operational lifetime of the ES shall be at least 60 minutes | Pass  |
|  Performance in Operational Temperature and Humidity Test | Confirm that the ES performance remains optimal at operational temperature and humidity boundary conditions | The ES shall meet predefined electrical performance criteria while exposed to operational temperature [15°C –35°C] and humidity [85% RH] conditions | Pass  |
|  Physical Parameters Test | Confirm that the weight of the device is within the range specified in the design requirements | The total weight of the ES shall be < 50g | Pass  |
|  Performance in Presence of Metal Retractor Test | Ensure the performance of the ES is not impacted due to the presence of a metal retraction surgery tool | The ES performance shall not be affected by more than ±5% due to the presence of a metal retraction surgery tool | Pass  |

Table 7. Summary of Bench Testing Performed on the Disposable Patch (DP)

|  Test | Test Purpose | Acceptance Criteria | Result  |
| --- | --- | --- | --- |
|  Adhesion Integrity | Evaluate the adhesion integrity of the device | The detachment force shall be > 5N | Pass  |
|  Bending Durability Test | Ensure that the DP is able to retain mechanical integrity and durability when exposed to bending forces which may be encountered during typical use | Following bending durability testing, the DP shall meet predefined electrical performance criteria | Pass  |

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Table 8. Summary of Bench Testing Performed on the Activation Chip (AC) Model #2364

|  Test | Test Purpose | Acceptance Criteria | Result  |
| --- | --- | --- | --- |
|  Physical Parameters Test | Ensure that the physical dimensions of the DP fit the anatomical variability which would be encountered during normal use | The fully assembled DP shall meet predetermined physical dimensions: - Length: ≤ 56mm - Width: 74mm – 95mm | Pass  |
|  Test | Test Purpose | Acceptance Criteria | Result  |
| --- | --- | --- | --- |
|  Physical Parameters | Ensure the device complies with its relevant design requirements | The fully assembled AC Model #2364 shall meet predetermined physical dimensions: - Height: < 23mm - Diameter: < 33mm | Pass  |
|  Storage Conditions Test | Confirm that the device remains fully functional and safe for use when stored at predefined temperature and humidity conditions | Following exposure to storage conditions of temperature [5°C – 40°C] and humidity [up to 85%], the AC Model #2364 shall meet visual and electrical performance criteria: | Pass  |
|  LED Visibility Test | Verify the presence of LED visibility for all applicable modes (red, yellow and green) | LED indication shall be visible in an indoor ambient lighting environment at an angle of up to 70° and a distance of up to 1m | Pass  |
|  Stimulation Treatment Test | Confirm that the AC interacts as required upon connection/disconnection from the DP, drives a stimulation pulse through the DP with the configurable set of parameters determined using the Sleep Lab App, and is able to produce a pulse with sufficient charge and peak current values | The AC Model #2364 shall meet the predetermined acceptance criteria for each type of AC stimulation test: AC/DP electrical interface, AC stimulation parameters, and system performance | Pass  |
|  Battery Functionality Test | Confirm that the AC battery is able to: power the AC, be recharged, fully charge in less than four hours, and meet certain performance criteria during an operational lifetime of at least eight hours between charges | A depleted AC battery shall be fully charged in less than four hours. The AC shall have an operational lifetime of at least eight hours between charges with predefined stimulation parameters and conditions. | Pass  |

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Table 9. Summary of Bench Testing Performed on the CU Model #2238

|  Test | Test Purpose | Acceptance Criteria | Result  |
| --- | --- | --- | --- |
|  Bluetooth Low Energy (BLE) Communication Test | Ensure the AC Bluetooth low energy (BLE) interface enables the device to communicate with a paired device at a distance of up to five meters and that the AC sends an acknowledgement message to the transmitting device upon receiving a message from a paired device over the BLE interface | The AC Model #2364 BLE interface shall enable the AC to communicate with a paired device located in a distance of up to five meters. Communication is verified based on reading and writing transactions.The AC Model #2364 BLE connection shall achieve a 95% success rate for 100 “Read Genio® AC” or “Stop Stimulation” transmissions, allowing up to five non-consecutive transmission errors for each set of communication transactions (reading or programming). | Pass  |
|  Sensors Functionality Test | Ensure that the sensors of the device will record data upon receiving a command from a paired device and send the paired device this date over BLE. | The Sleep Lab App shall save a file with the sensor's Raw Data sent by the AC Model #2364 over BLE connection in the Repeater | Pass  |
|  Weight Test | Confirm that the weight of the device is in compliance with the established design requirements | The AC Model #2364 shall weigh < 90g | Pass  |
|  Vibration Durability Test | Show compliance with ISO 14708-1:2014 | All tested devices shall meet visual and functionality requirements prior to and post vibration | Pass  |
|  Performance in Operational Temperature and Humidity Test | Ensure that the device remains fully functional and safe for use within the defined operational temperature and humidity conditions | The AC Model #2364 shall pass predefined electrical performance and visual criteria while exposed to operational temperature [15°C - 35°C] and humidity [85% RH] conditions | Pass  |

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Table 10. Summary of Device Interface Bench Testing

|  Test | Test Purpose | Acceptance Criteria | Result  |
| --- | --- | --- | --- |
|  AC/DP Contact Resistance Test | Ensure that when attached to the DP, the interface allows for an efficient transmission of electromagnetic energy between the two devices | All of the AC/DP interface measurements shall have an electrical contact with I resistance of < 0.2Ω at 1.5A DC | Pass  |
|  AC/DPC Contact Resistance Test | Ensure that the device remains fully functional and safe for use when stored at predefined temperature and humidity conditions | All of the AC/DPC interface measurements shall have an electrical contact with I resistance of < 0.2Ω at 1.5A DC | Pass  |

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# C. EMC and Electrical Safety Testing

The Genio® System 2.1 was evaluated for EMC and electrical safety testing in accordance with the IEC 60601 standards. A summary of the standards to which each Genio® System 2.1 device complies is provided in Table 11.

Table 11. Summary of Genio® System 2.1 EMC and Electrical Safety Testing

|  Test | Test Purpose | Acceptance Criteria | Device | Result  |
| --- | --- | --- | --- | --- |
|  Electromagnetic Compatibility (EMC)/Immunity Testing | Verify the device meets international standard for electromagnetic compatibility | IEC 60601-1-2:2014 | IS Model #2954 | Pass  |
|   |   |   |  ES  |   |
|   |   |   |  DP  |   |
|   |   |   |  AC Model #2364  |   |
|   |   |   |  CU Model #2238  |   |
|  Electromagnetic Interference (including Wireless Coexistence) | Verify that the device maintains its intended use and does not result in an unacceptable risk due to susceptibility to electrical influences from external electromagnetic fields, including Radio Frequency (RF) signals. | ISO 14708-3:2017 | IS Model #2954 | Pass  |
|   |   |  IEEE/ANSI C63.27:2017 | IS Model #2954 | Pass  |
|   |   |   |  DP  |   |
|   |   |   |  AC Model #2364  |   |
|   |   |   |  CU Model #2238  |   |
|   |   |   |  Repeater  |   |
|   |   |  RTCA DO-160G | IS Model #2954 | Pass  |
|   |   |   |  AC Model #2364  |   |
|   |   |  AIM7351731:2021 | IS Model #2954 | Pass  |

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|  Test | Test Purpose | Acceptance Criteria | Device | Result  |
| --- | --- | --- | --- | --- |
|   |  |  | ES |   |
|   |   |   |  AC Model #2364  |   |
|  Electrical Safety | Verify the device meets international standards for electrical safety | IEC 60601-1:2005/AMD1:2012 | IS Model #2954 | Pass  |
|   |   |   |  ES  |   |
|   |   |   |  DP  |   |
|   |   |   |  AC Model #2364  |   |
|   |   |   |  CU Model #2954 | Pass  |
|   |   |  IEC 60601-1-11:2015 | DP  |   |
|   |   |   |  AC Model #2364  |   |
|   |   |   |  CU Model #2238  |   |
|   |   |  IEC 60601-2-10:2016 | IS Model #2954 | Pass  |
|   |   |   |  ES  |   |
|   |   |   |  AC Model #2364  |   |
|   |   |   |  CU Model #2238  |   |
|   |   |  ISO 14708-1:2014 ISO 14708-3:2017 | IS Model #2954 | Pass  |

# D. MRI Safety Evaluation

The implantable component of the Genio® System 2.1 (IS Model #2954) was evaluated in accordance with ISO/TS 10974:2018 - Assessment of the safety of magnetic resonance imaging for patients with an active implantable medical device and standard test methods and found to be MR Conditional. A summary of MRI testing conducted on the IS Model #2954 is provided in Table 12.

Table 12. Summary of MRI Testing - IS Model #2954

|  Hazard | Test Method/Standard | Acceptance Criteria | Results  |
| --- | --- | --- | --- |
|  Magnetically induced displacement force | Measurement of B0 induced force applied on the implant [ASTM F2052-15] | A deflection angle of < 45°. In case the deflection angle exceeds 45°, a rationale can be provided considering a counter force applied by the sutures with a safety factor of 2 | Pass α=1.0°  |

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|  Hazard | Test Method/Standard | Acceptance Criteria | Results  |
| --- | --- | --- | --- |
|  Magnetically induced torque | Measurement of B_{0} induced torque applied on the implant [ASTM F2213-17] | Maximum magnetically induced torque < worst-case gravity torque of the test object (~1.63mNm) | Pass τ_{max}=165.49μNm  |
|  Gradient induced vibration (malfunction) | Exposure of the implant to a set of gradient intensive clinical Echo Planar Imaging (EPI) sequences for a total scanning time of 2.5hrs to investigate device damage or malfunction caused by gradient induced vibration [ISO/TS 10974:2018 §10] | The implant shall not suffer from loss of functionality or reduction in performance following the combined exposure to the switched gradient and static magnetic field | Pass; no device damage or performance degradation was detected after exposure  |
|  Device malfunction | B_{0} induced malfunction: exposure of the device to the static magnetic field in three orientations followed by a full functionality test [ISO/TS 10974:2018 §14] | The implant shall not suffer from loss of functionality or reduction in performance following exposure to the static magnetic field | Pass; no device damage or performance degradation was detected after exposure  |
|  Device malfunction | Gradient induced malfunction: measurement of gradient induced malfunction of the implant due to the gradient magnetic field of an MR scanner using a radiated test method and injected test method [ISO/TS 10974:2018 §16] | The implant shall not suffer from loss of functionality or reduction in performance following the exposure to the switched gradient field | Pass; no device damage or performance degradation was detected after exposure  |

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|  Hazard | Test Method/Standard | Acceptance Criteria | Results  |
| --- | --- | --- | --- |
|   | RF induced malfunction: exposure of the device to radiated RF signals of 64MHz and 128MHz followed by a functionality test of the tested device [ISO/TS 10974:2018 §15] | The implant shall not suffer from loss of functionality or reduction in performance following exposure to the RF fields | Pass; no device damage or performance degradation was detected after exposure  |
|   |  Combined fields test 1.5T: exposure of the implant to a combination of the three EM fields (static magnetic B_{0}, switching gradient magnetic field dB/dt, RF field) of the MR system (1.5T) in order to evaluate its robustness against the resulting EM interferences followed by a functionality test of the device [ISO/TS 10974:2018 §17] | The implant shall not suffer from loss of functionality or reduction in performance following exposure to the three EM fields | Pass; no device damage or performance degradation was detected after combined field exposure  |
|  Device malfunction | Combined fields test 3T: exposure of the implant to a combination of the three EM fields (static magnetic B_{0}, switching gradient magnetic field dB/dt, RF field) of the MR system (3T) in order to evaluate its robustness against the resulting EM interferences followed by a functionality test of the device [ISO/TS 10974:2018 §17] | The implant shall not suffer from loss of functionality or reduction in performance following exposure to the three EM fields | Pass; no device damage or performance degradation was detected after combined field exposure  |

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|  Hazard | Test Method/Standard | Acceptance Criteria | Results  |
| --- | --- | --- | --- |
|  Gradient induced heat | Exposure of the implant to a known switched gradient magnetic field while simultaneously measuring the temperature at different locations near the surface. The test device will be placed in the worst-case orientations to the magnetic flux vector of the pulsed magnetic field simulator [ISO/TS 10974:2018 §9] | The gradient-induced heating Δ of temperature compared to the initial test temperature after an exposure of 30 minutes is below or equal to 2°C, or a CEM43 threshold of 40 is reached (ISO 14708-3:2017 §17) | Pass
ΔT=0.2°C for 34.6dB/dt_{rms}
ΔT=0.6°C for 42.0dB/dt_{rms}  |
|  RF induced heating | An estimate maximum power position around the implant and its hot spots is determined and EM modeling is used to determine the electrical field in the implant volume. The RF power deposition is determined according to the Tier 2 approach [ISO/TS 10974:2018 §8] | The 60 minute temperature rise is below or equal to 6°C | Pass
5.9°C for 1.5T 5.9°C for 3T  |
|  Unintended stimulation | Gradient induced lead voltage: injection of induced voltage to an IS electrical circuit and measurement of the output signal of the implant (including Leakage Test and Gradient Rectified Test) [ISO/TS 10974:2018 §13] | – Shannon factor < 1.7
– Charge injection density < 50μC/cm^{2}
– DC current < 75μA/cm^{2} | Pass
Test Case 1: Leakage test=7.86nC
Rectified test=23.6μA

Test Case 2: Leakage test
0.2ms=37.8±4.8nC
1.0ms=6.9±0.9nC
Rectified test
(0.2ms)=0.84±0.10μA  |

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|  Hazard | Test Method/Standard | Acceptance Criteria | Results  |
| --- | --- | --- | --- |
|  Unintended stimulation | RF induced voltages/RF rectification: injection of RF signals into the IS electrical circuit in order to measure the rectified current and induced voltages resulting from this exposure. A numerical model representing the IS in its nominal production configuration is used for definition of input parameters [ISO/TS 10974:2018 §15] | - Shannon factor < 1.7 - Charge injection density < 50μC/cm2 - DC current < 75μA/cm2 | Pass; 64MHz – 860.1nC (net charge of 24.1nC) 128MHz – 62.97nC (net charge of 1.89nC)  |
|  Image artifact | Measurement of MR image artifacts of the IS due to influences of the field lines of the magnetic field of an MR scanner by the implant [ASTM F2119-07(2013)] | Characterization test only, no pass/fail criteria | N/A; for characterization purposes only  |

# E. Software and Cybersecurity

The Genio® System 2.1 devices which utilize software (AC Model #2364, ES, Repeater with Sleep Lab Application and the Smartphone Application) comply with IEC 62304:2015 – Medical device software – Software life cycle processes and any applicable cybersecurity requirements.

The device conformed to the following FDA guidance documents:

- Content of Premarket Submissions for Device Software Functions: June 2023
- Cybersecurity in Medical Devices: Quality System Considerations and Content of Premarket Submissions: September 2023

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# F. Packaging and Shelf-Life

The shelf-life for all Genio® System 2.1 devices was established based on various evaluations. Testing for sterile devices were conducted in accordance with ISO 11607-1:2019 – Packaging for terminally sterilized medical devices – Part 1 : Requirements for materials, sterile barrier systems and packaging systems and ISO 11607-2:2019 – Packaging for terminally sterilized medical devices – Part 2 : Validation requirements for forming, sealing and assembly process standards. Information on the shelf-life for the Genio® System 2.1 devices is detailed in Table 13 below.

Table 13. Summary of Genio® System 2.1 Shelf-Life and Sterility

|  Device | Sterile/Non-Sterile | Shelf-Life  |
| --- | --- | --- |
|  Implantable Stimulator Model #2954 | Sterile | 2 years  |
|  External Stimulator | Sterile | 1 year  |
|  Disposable Patch | Non-Sterile | 16 months (sealed bag) 15 days (opened bag)  |
|  AC Model #2364 | Non-Sterile | 1 year  |
|  CU Model #2238 | Non-Sterile | 1 year  |

# G. Sterilization

All sterile products of the Genio® System 2.1 (IS, IS Model #2954 and ES) are sterilized using Ethylene Oxide (EO) and have a sterility assurance level (SAL) of at least  $10^{-6}$  and complies with the requirements of ISO 11135:2014 – Sterilization of health care products – Ethylene oxide – Requirements for development, validation and routine control of a sterilization process for medical devices.

# H. Human Factors

Human factors validation testing was completed for the Genio® System 2.1 per FDA's 2016 Guidance – Applying Human Factors and Usability Engineering to Medical Devices and in accordance with IEC 62366-1:2015_AMD1:2020 – Medical Devices – Part 1: Application of usability engineering to medical devices. Human factors validation was performed to demonstrate that the user interface for the Genio® System 2.1 has been designed such that any use errors that could result in harm or impact treatment have been eliminated or reduced as far as possible. Results of the human factor validation tests demonstrated that Genio® System 2.1 can be used by the intended users without serious use errors or problems, for the intended uses and under the expected use conditions. An overview of the Genio® System 2.1 the human factors validation tests are provided in Table 14.

Table 14. Overview of Genio® System 2.1 Human Factors Validation Tests

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|  Intended User | Purpose of Evaluation | Method of Evaluation | Device(s) Evaluated  |
| --- | --- | --- | --- |
|  Patient/Home User | Evaluate user performance based critical tasks related to daily use of the Genio® System 2.1 (e.g., DP placement, use of Smartphone App) | Simulated Use | - AC Model #2364 - DP - CU Model #2238 - Smartphone App  |
|   |  Evaluate user understanding of critical tasks which could not be observed during simulated use (e.g., warnings, precautions) | Knowledge Questions  |   |
|  Surgeon | Evaluate user performance based critical tasks related to the implantation procedure specific to human anatomy (e.g., implant placement, suturing) | Simulated Use - Cadaver | - IS Model #2954 - ST  |
|   |  Evaluate user performance based critical tasks related to the implantation procedure which require in vivo assessment (e.g., verification of implant placement) | Simulated Use - Animal | - IS Model #2954 - ES - AC Model #2364/DP  |
|   |  Evaluate user understanding of critical tasks which could not be observed during simulated use (e.g., contraindications, warnings) | Knowledge Questions | - IS Model #2954 - ST - ES - AC Model #2364/DP  |

# I. Animal Studies

Acute and chronic animal studies were conducted on swine animal model to evaluate the safety and performance of the Genio® System 2.1 prior to initiating clinical studies. Both studies were performed in compliance with 21 CFR 58 – Good Laboratory Practice for Nonclinical Laboratory Studies. A summary for each of these animal studies is provided in Table 15

Table 15. Summary of Genio® System 2.1 Animal Studies

|  Study Type | Study Purpose | Study Sample Size | Results  |
| --- | --- | --- | --- |
|  Acute Implantation Studies | Assess feasibility of the IS implantation procedure and device performance. | 1-2 porcine per study | The implantation procedures in all animals were completed successfully and uneventful. The overall Genio® System showed favorable usability and  |
|   |  |  | reversible. The IS model showed good usability and the device performance was excellent.  |
|  Human Implantation Studies | Assess the use of the IS implant and device performance. | 1-2000 | The use of the IS implant and device performance was excellent. The IS model showed good usability and the device performance was excellent.  |

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|  Study Type | Study Purpose | Study Sample Size | Results  |
| --- | --- | --- | --- |
|   |  |  | expected contraction of the genioglossus muscle and significant airway opening.  |
|  GLP Chronic Study – Migration and Stimulation Safety | - Evaluate the local effects of the IS on the target tissue (genioglossus muscle and hypoglossal nerve) under eight (8) weeks of periodic stimulation.
- Evaluate the implant’s location stability (i.e., migration) for a period of at least 12 weeks. | 6 porcine | Long term stimulation was considered a non-irritant to the tissue and caused minimal local effects. The device is stable and did not migrate over time.  |
|  GLP Chronic Study – Migration | Perform a comparative evaluation of the IS Model #2954 during implantation for eight (8) weeks, demonstrating that the implant remains in place without migration, and the implant positions between the IS Model #2954 to the original IS (1st Generation) are equivalent. | 6 porcine (4 IS Model #2954, 2 control) | There was no evidence of clinically relevant adverse pathological findings between control and test implanted animals. All implants were fully encapsulated, appeared stable, and were firmly secured to the surrounding tissues of the ventral tongue preventing any significant migration.  |

X. SUMMARY OF PRIMARY CLINICAL STUDY

The applicant performed a clinical study (“DREAM”) to establish a reasonable assurance of safety and effectiveness of bilateral Hypoglossal Nerve Stimulation with the Genio® System 2.1 to treat adult subjects with moderate to severe Obstructive Sleep Apnea (OSA) in the US, Belgium, Germany, and Australia under IDE G190068. Results from this clinical study were used to support the PMA approval decision. A summary of the clinical study is presented below.

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# A. Study Design

Patients were treated between October 14, 2020, and March 3, 2024. The database for this PMA reflected primary endpoint data collected through Jan 6, 2025, and included 115 implanted patients. There were 22 investigational sites.

The DREAM study was a multi-center, prospective, open-label, non-randomized, single arm clinical study to demonstrate the safety and effectiveness of the Genio® dual-sided hypoglossal nerve stimulation system in treating moderate to severe OSA over a period of 12 months post-surgery.

**Endpoints:** The study had two co-primary efficacy endpoints: the first measured the percentage of responders at 12 months based on a 50% reduction in AHI4 (Apnea-Hypopnea Index based on 4% oxygen desaturation) and a remaining AHI4 of less than 20, and the second measured the percentage of responders based on a 25% reduction in ODI4 (Oxygen Desaturation Index based on 4% desaturation), both assessed with fixed therapeutic settings on full-night Polysomnography (PSG). The objective was to demonstrate at least 50% responders for both AHI4 and ODI4 at 12 months, with the study considered successful if the null hypotheses were rejected for both endpoints.

**Sample Size:** Sample size calculations used a one-sample exact binomial test with 80% statistical power and a one-sided 2.5% significance level. For the AHI4 endpoint, N=85 evaluable subjects were required to demonstrate superiority over the pre-specified performance goal of 50% responder rate, assuming a true responder rate of 65% under the alternative hypothesis. The ODI4 endpoint required a larger sample size of N=98 evaluable subjects, assuming a true responder rate of 64%. To account for approximately 15% non-evaluable subjects due to anticipated dropouts and missing data, a total of N=115 subjects were enrolled and implanted in the study (98/0.85).

**Monitoring:** An independent Data Safety Monitoring Board (DSMB) was established to review trial data, including safety events, protocol deviations, and device deficiencies, consisting of 4 members: 3 voting physicians (ENT/Sleep Medicine experts) and one non-voting biostatistician. A Clinical Events Committee (CEC) was also set up for this study to ensure objective and centralized review and adjudication of clinical adverse events occurring in this study. The CEC was composed of at least 3 members (3 physicians from the field of ENT and/or Sleep Medicine), who were independent from the study conduct. The CEC reviewed and adjudicated clinical adverse events.

**Core Lab:** All PSGs were scored by an independent Core Lab following AASM guidelines to minimize bias. Drug-Induced Sleep Endoscopy (DISE) was conducted on enrolled subjects with qualifying AHI scores to screen for complete concentric collapse (CCC).

**Device Under Test:** The study was conducted using the 1st Generation model of the IS ("original IS"). Although the original IS and IS Model #2954 differ in certain

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characteristics, the two versions of the Genio® System implant were considered functionally equivalent in key areas such as: electronic circuitry, stimulation parameters used, active stimulation area of the electrodes, mode of communication with the AC Model #2364, and use of external components. The IS Model #2954 incorporated several design improvements including a hermetic ceramic enclosure (versus Parylene coated PEEK frame), a single-shoulder design for increased paddle flexibility (reduced from double-shoulder), slight increases in main body thickness and mass, and an extended service life from 3 years to at least 12 years. Based on all the non-clinical and pre-clinical testing conducted for IS Model #2954, it was concluded that the changes made for the IS Model #2954 did not impact the performance or functionality of the implant when compared to the original IS. Considering both the similarities between the original IS and the IS Model #2954 as well as the assessment of the design changes, the clinical data obtained with the original IS during the DREAM IDE study was considered leverageable for the IS Model #2954.

## 1. Inclusion and Exclusion Criteria

Enrollment in the DREAM study was limited to patients who met the following inclusion criteria:

- 22 to 75 years of age
- Body mass index of ≤ 32 kg/m²
- Cricomental space positive (≥ 0 cm)
- Have either not tolerated, have failed or refused positive airway pressure (PAP) treatments
- Moderate to severe OSA 15≤AHI4≤65 where combined central and mixed AHI &lt; 25% of the total AHI
- Non-supine AHI &gt; 10 events on the screening PSG or subject has either not tolerated, has failed or refused positional therapy
- Written informed consent for performing any study specific procedure
- Willing and capable of complying with all study requirements
- Willing to consent to long term follow-up of 5 years post-surgery

Patients were not permitted to enroll in the DREAM study if they met any of the following exclusion criteria:

- Inadequately treated sleep disorders other than OSA that would confound functional sleep assessment
- Night shift workers
- Taking medications that may alter consciousness, the pattern of respiration, or sleep architecture
- Major anatomical or functional abnormalities that would impair the ability of the Genio® System to treat OSA
- Significant comorbidities that contraindicate surgery or general anesthesia
- Prior surgery or treatments that could compromise the effectiveness of the Genio® System

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- Have an Active Implantable Medical Device (AIMD) even if the device can be temporarily turned off
- Participation in another clinical study with an active treatment arm that could confound the results of the DREAM study
- Plan to become pregnant, currently pregnant, or breastfeeding during the study period
- The study did not include patients with complete concentric collapse at the soft palate level

## 2. Follow-up Schedule

The patients were scheduled for screening and baseline evaluations before implant and follow up post-surgery up to 12 months. Table 16 below lists the schedule of events up to and including the assessment of the primary and secondary endpoints at 6-months post-surgery.

Table 16. List of study procedures until the 6-month follow-up visit

|  Test / Evaluation | Screening | Baseline | Implant | Week 1 Post-Op | Month 2 Follow Up | Month 3 Follow Up | Month 4 Follow Up | Month 5 Follow Up | Month 6 Follow Up  |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
|  Visit Window (Days) | -90 | -90 | 0 | ±5 | ±14 | ±14 | ±14 | ±14 | ±14  |
|  Informed Consent Form (ICF) Signature | X |  |  |  |  |  |  |  |   |
|  Check Eligibility Criteria | X |  |  |  |  |  |  |  |   |
|  Demographic Data and Medical History | X |  |  |  |  |  |  |  |   |
|  Pregnancy Test | X^{1} |  |  |  |  |  |  |  |   |
|  Surgical Consult and Mallampati Score | X |  |  |  |  |  |  |  |   |
|  Vital Signs | X | X | X^{2} | X | X | X | X | X | X  |
|  Physical Examination | X |  |  |  |  |  |  |  |   |
|  Neck Circumference | X |  |  |  |  |  |  |  |   |
|  Functional Tongue Exam & Neurological Assessment | X |  | X^{2} | X | X | X | X | X | X  |
|  EAT-10 questionnaire | X |  | X^{2} | X | X | X | X | X | X  |
|  VHI-10 questionnaire | X |  | X^{2} | X | X | X | X | X | X  |
|  Reflux Symptom Index questionnaire | X |  | X^{2} | X | X | X | X | X | X  |
|  Height (screening only) & Weight | X |  | X |  |  |  |  |  | X  |
|  Cricomental Space | X |  |  |  |  |  |  |  |   |
|  Snoring Scoring, FOSQ-10, ESS and SNORE-25 Questionnaires | X |  |  |  |  |  |  |  | X  |
|  DISE | X^{4,5} |  |  |  | X |  |  |  | O^{3}  |

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|  Test / Evaluation | Screening | Baseline | Implant | Week 1 Post-Op | Month 2 Follow Up | Month 3 Follow Up | Month 4 Follow Up | Month 5 Follow Up | Month 6 Follow Up  |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
|  Home Sleep Test |  |  |  |  |  | O |  | O |   |
|  In-lab PSG | X | X |  |  |  |  | X |  | X  |
|  Implantation Procedure |  |  | X |  |  |  |  |  |   |
|  Subject Card |  |  | X^{7} |  |  |  |  |  |   |
|  Pain Visual Analog Scale (VAS) |  |  | X^{7} | X | X |  |  |  |   |
|  Device Activation and Subject Training |  |  |  |  | X^{6} |  |  |  |   |
|  Awake Titration |  |  |  |  | X | X | X | X | X  |
|  Asleep Titration |  |  |  |  |  |  | X |  | X  |
|  Usability Questionnaire |  |  |  |  |  |  | X |  | X  |
|  Subject Satisfaction Questionnaire |  |  |  |  |  |  |  |  | X  |
|  Dispense / Collect Subject Diary^{8} |  |  |  |  | X | X | X | X | X  |
|  Device Check |  |  |  |  | X | X | X | X | X  |
|  Adverse Events | X | X | X^{7} | X | X | X | X | X | X  |
|  Device Deficiencies | X | X | X | X | X | X | X | X | X  |
|  Concomitant Medications | X | X | X^{7} | X | X | X | X | X | X  |

X = required
O = optional

1. If applicable (only for women of childbearing potential). A urine pregnancy test is sufficient to determine participation. A serum pregnancy test instead of a urine pregnancy test should only be considered if required by country, local or ethnic committee regulations. Female subjects are strongly advised to use effective contraception during the course of the research.
2. EAT-10, Reflux Symptom Index, VHI-10, Vital signs and functional tongue exam &amp; neurological assessments will be completed both prior to surgery and prior to discharge.
3. In case DISE is performed prior to the PSG (where applicable), DISE shall be conducted at least 12 hours prior to the PSG.
4. Screening DISE can only be performed if the Core lab confirmed subject has successfully passed the screening PSG.
5. A previously performed DISE can be used as the Screening DISE, if it has been performed within 6 months prior to enrollment, the video is available and can be scored by the Core Lab, and if from the date of the DISE to enrollment date:
a. there has been no change in subject BMI &gt;1kg/m²,
b. the subject has not undergone upper airway surgery, including nasal surgery, and
c. there has been no significant change in medical history or other reason that would impact the results of the DISE, as determined by the Investigator.
6. Subject may be retrained if needed.
7. Assessments to be performed after surgery and prior to discharge.
8. Subjects will complete the diary daily.
Note: Routine tests could be done before anesthesia and surgery, per each hospital's standard of care.

At the 6-month visit, the investigator assessed if the therapy was optimized based on a positive change in AHI and ODI from baseline. If therapy was considered optimized, study visits were

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scheduled at 9- and 12-months. If the therapy was not optimized, study visits were scheduled at 8-, 10- and 12-months. The procedures that were performed after the 6-month visit are presented in Table 17 below.

Table 17. List of study procedures after the 6-month follow-up visit

|  Test / Evaluation | If therapy not optimized @ 6-month |   | If therapy optimized @ 6-month | Month 12 Follow Up  |
| --- | --- | --- | --- | --- |
|   |  Month 8 Follow Up | Month 10 Follow Up | Month 9 Follow Up  |   |
|  Visit Window (Days) | ±14 | ±14 | ±14 | ±30  |
|  Vital Signs | X | X | X | X  |
|  Functional Tongue Exam & Neurological Assessment | X | X | X | X  |
|  EAT-10 questionnaire | X | X | X | X  |
|  VHI-10 questionnaire | X | X | X | X  |
|  Reflux Symptom Index questionnaire | X | X | X | X  |
|  Weight |  |  |  | X  |
|  Snoring Scoring, FOSQ-10, ESS and SNORE-25 Questionnaires | X | X | X | X  |
|  In-lab PSG | X | X | X | X  |
|  Asleep Titration | X | X | X |   |
|  DISE | O¹ |  | O¹ |   |
|  Awake Titration | X | X | X | X  |
|  Usability Questionnaire | X | X | X | X  |
|  Satisfaction Questionnaire |  |  |  | X  |
|  Dispense / Collect Subject Diary² | X | X | X | X  |
|  Device Check | X | X | X | X  |
|  Adverse Events | X | X | X | X  |
|  Device Deficiencies | X | X | X | X  |
|  Concomitant Medications | X | X | X | X  |
|  Study Exit | X³ | X³ | X³ | X³  |

X = required
O = optional
¹ In case DISE is performed prior to the PSG (where applicable), DISE shall be conducted at least 12 hours prior to the PSG.
² Subjects will complete the diary daily.
³ If applicable.

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# 3. Clinical Endpoints

## Safety Endpoints

With regards to safety, evaluation was conducted using the incidence of device and/or procedure serious events recorded during the study for a period of 12 months post-surgery. All adverse events were adjudicated by an independent Clinical Events Committee (CEC). An independent Data &amp; Safety Monitoring Board (DSMB) reviewed the accumulated safety data and assessed the validity and integrity of the clinical study data.

## Co-Primary Effectiveness Endpoints

- AHI4: percentage of responders at 12 months based on AHI4, a responder being defined as a participant who satisfies the following criteria: at least a 50% reduction from the average AHI4 of screening and baseline to 12 months post-surgery and a residual AHI4 less than 20 at the 12-month visit (i.e., "Sher Criteria"), as measured with fixed therapeutic settings using full-night PSG (all scored by an independent core laboratory)
- ODI4: percentage of responders at 12 months based on ODI4, a responder being defined as a participant who satisfies the following criterion: at least a 25% reduction from the average ODI4 of screening and baseline to 12 months post-surgery, as measured with fixed therapeutic settings using full-night PSG (all scored by an independent core laboratory).

## Secondary Effectiveness Endpoints

Six secondary effectiveness endpoints were identified in the DREAM study protocol:

1. Mean change in the OSA-specific quality of life measured by the SNORE-25 instrument at the 12-month visit compared to screening.
2. Mean change in the hypoxemic burden measured by the percentage of sleep time with oxyhemoglobin saturation &lt; 90% at the 12-month PSG compared to the average of screening and baseline.
3. Mean change in the intermittent hypoxia measured by the ODI4 at the 12-month PSG compared to the average of screening and baseline.
4. Mean change in the sleep-specific function measured by the Functional Outcomes of Sleep Questionnaire (FOSQ-10) at the 12-month visit compared to screening.
5. Mean change in the sleep propensity measured by the ESS at the 12-month visit compared to screening.
6. Mean change in OSA severity measured by the AHI4 at the 12-month PSG compared to the average of screening and baseline.

## Success/failure criteria

Patient success was defined as clinically significant reduction in OSA and improvements in overall sleep quality.

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The study objective was to demonstrate at least 50% responder rates at 12 months (pre-specified performance goal) for both co-primary endpoints: AHI4-based responders (first co-primary endpoint) and ODI4-based responders (second co-primary endpoint). Study success required rejection of the null hypotheses for both co-primary endpoints as defined below.

The statistical hypotheses for the first co-primary endpoint were the following:

- H01 (null hypothesis): Percentage of responders at Month 12 based on AHI4 (“Sher Criteria”) &lt; 50%
- H11 (alternative hypothesis): Percentage of responders at Month 12 based on AHI4 (“Sher Criteria”) ≥ 50%

The statistical hypotheses for the second co-primary endpoint were the following:

- H02 (null hypothesis): Percentage of responders at Month 12 based on ODI4 &lt; 50%
- H12 (alternative hypothesis): Percentage of responders at Month 12 based on ODI4 ≥ 50%

To claim success in meeting secondary effectiveness endpoints, all six secondary endpoints described above were required to be met to preserve the overall Type I error rate of 2.5%.

## B. Accountability of PMA Cohort

A total of 687 subjects were enrolled according to protocol-defined procedures. A total of 568 subjects (82.7%) were screen failures and did not receive an implant. A total of 115 subjects (16.7%) from 19 investigative sites had an attempted implant with 113 (16.4%) of those successfully implanted with the Genio® System. Figure 14 includes accountability of the subject disposition and analysis cohorts.

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![img-13.jpeg](img-13.jpeg)
Figure 14: Subject disposition, analysis cohorts.

The following sets of population were used in the analysis of the study: the Enrolled set, the Safety (SAF) set, the Full Analysis (FA) set, and the Per Protocol (PP) set.

# Enrolled Set  $(N = 687)$

The Enrolled set included all subjects with informed consent form signed. This set was used for the listings of adverse events as some adverse events may have started before the implant procedure.

# Safety Set (SAF)  $(N = 115)$

The SAF set included all subjects who underwent the implant procedure (implant surgery started, whether the device was implanted or not). This set was used for description of demographic and baseline characteristics as well as for analyses of safety assessments.

# Full Analysis Set (FAS)  $(N = 110)$

The FA included all subjects who successfully completed the implant procedure. Additionally, the three subjects successfully implanted in Australia were not included in FA set due to the unmonitored status of their data (Good Clinical Practice (GCP) deviation). They were subsequently excluded from the effectiveness analyses.

# Per Protocol Set (PP)  $(N = 88)$

The per-protocol set (PP) included all subjects from the FA set who performed the 12-month PSG with available values for primary endpoints (AHI4 and ODI4) and without any critical major protocol deviations. In case the PP set differs from the FA set, the PP set may be used for description of demographic and baseline characteristics as well as for analyses of effectiveness assessments.

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# Statistical Analysis of Analysis Sets

The SAF will be used for the analysis of safety assessments. Effectiveness assessments will be analyzed on the FA (primary analysis), on the PP (sensitivity analysis), and on the SAF (sensitivity analysis for co-primary endpoints).

At the time of database lock, of the 115 patients enrolled in the PMA study, 93 patients were available for analysis at the completion of the study, the 12-month post-operative visit. Of the 115 subjects who underwent attempted implantation, 93 completed the M12 clinic visit and 89 also completed an M12 PSG. The remaining 27 patients did not undergo a final PSG due to: GCP-related withdrawals (3), aborted surgery (2), major protocol deviation (1), lost to follow-up (4), consent withdrawal (6), and missed M12 visits due to adverse events, device deficiencies, or visits occurring outside the protocol window (10). Table 18 summarizes the cumulative implanted subject accountability by visit.

Table 18. Cumulative Implanted Subjects Accountability by Visit – SAF (N=115)

|  Subjects | Implant | 1-wk | M2 | M3 | M4 | M5 | M6 | M8* | M9 | M10 * | M12  |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
|  Visit at interval | 115 (100%) | 114 (99.1 %) | 112 (97.4%) | 109 (94.8 %) | 107 (93.0%) | 98 (85.2%) | 104 (90.4 %) | 52 (45.2 %) | 45 (39.1 %) | 51 (44.3 %) | 93 (80.9 %)  |
|  Visit in window | 55 | 107 | 105 | 100 | 92 | 87 | 78 | 33 | 38 | 38 | 77  |
|  Visit outside window | 60 | 7 | 7 | 9 | 15 | 11 | 26 | 19 | 7 | 13 | 16  |
|  Missed Visit | 0 | 1 | 0 | 2 | 2 | 9 | 1 | 4 | 1 | 5 | 2  |

* M8 and M10 visits conducted if therapy not optimized at Month 6 visit.

## C. Study Population Demographics and Baseline Parameters

The demographics of the 115 subjects implanted with the Genio® system are presented in Table 19.

Table 19. DREAM subject demographics

|  Demographic Outcomes | Mean ± SD (N = 115) | Median (Min; Max)  |
| --- | --- | --- |
|  Age, year | 56.8 ± 7.3 | 57 (36;71)  |
|  Male, gender | 70.4% (81/115) | NA  |
|  Body Mass Index, kg/m² | 28.50 ± 2.63 | 28.7 (21.7; 32.0)  |
|  BP Systolic, mmHg | 132.6 ± 16.5 | 131  |
|  BP Diastolic, mmHg | 79.9 ± 10.0 | 80  |

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|  Neck Circumference, cm | 40.55 ± 5.73 | 40.6 (30.5; 86.4)  |
| --- | --- | --- |
|  Race: Caucasian | 93.9% (108/115) | NA  |
|  Race: Asian | 0.9% (1/115) | NA  |
|  Race: Black or African American | 3.5% (4/115) | NA  |
|  Race: Other | 1.7% (2/115) | NA  |

Even though most patients in the study were male and Caucasian, it is expected that the Genio® System would be effective in other populations as the mechanism of action involving bilateral hypoglossal nerve stimulation to activate tongue muscles is consistent across demographic groups.

Table 20. Baseline AHI ranges (FAS N=110)

|  Baseline AHI ranges | n (%)  |
| --- | --- |
|  X ≤ 5 | 0 (%)  |
|  5 < X < 15 (mild OSA) | 10 (9.1%)  |
|  15 ≤ X < 30 (moderate OSA) | 60 (54.5%)  |
|  X ≥ 30 (severe OSA) | 40 (36.4%)  |

The study included 10 subjects with a baseline AHI of less than 15 events/hr. This outcome was a result of the following aspects of the study design -

- All subjects had to meet the inclusion criteria of at least moderate OSA in their Screening PSG; no such requirement was placed on the pre-operative PSG
- Night-to-night variability of AHI can skew or misrepresent the burden of OSA even if AHI4 and supine sleep times are similar across multiple nights
- Results from the two PSGs were averaged to obtain a baseline AHI

Although this computation was not used in the study, when their historical PSGs were also included in computing the average AHI, most of these subjects presented with moderate OSA. Therefore, the inclusion of these subjects in the study was justified.

## D. Safety and Effectiveness Results

### 1. Safety Results

The analysis of safety was based on an assessment of all reported adverse events.

### Adverse events that occurred in the PMA clinical study

Safety parameters were evaluated based on the incidence of device or procedure-related adverse events recorded during the 12-month post-surgical period. A total of 394 adverse events occurred during the 12-month post-implantation period, including 252 non-serious adverse events in 85 subjects (73.9%) and 13 serious adverse events in 13 subjects (11.3%)* related to device or procedure. All adverse events observed in the study are summarized in Table 21 below.

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Table 21: Overview of Adverse Events through M12 visit – Safety Set (N=115)

|  Adverse events | Non-device-related
Non-procedure-related
m (n, %) | Device or Procedure-related
m (n, %)  |
| --- | --- | --- |
|  Non-serious | 126 (59, 51.3%)
(AE) | 252 (85, 73.9%)
(AE)  |
|  Serious | 3 (2, 1.7%)
(SAE) | 13 (13, 11.3%)*
(SAE)  |

n: number of subjects with at least one event
% = (n row / N column x 100)
m: number of events
Note: A same subject can have more than one event
* The 13 serious adverse events include 1 case of repositioning surgery (procedure-related) and 4 cases of replacement surgery (device-related) that were neither classified by the Study Investigator nor adjudicated by the Clinical Events Committee (CEC) as serious adverse events. If these events are excluded from the list of SAEs, the overall incidence of device- and/or procedure-related SAEs up 12-months would be 7% (device-related: 1.7%, device- and procedure-related: 0.9%, procedure-related: 4.3%). See Table 24 for description of SAEs.

All serious and non-serious adverse events observed in the clinical study through the 12-month follow-up in the safety set of 115 patients are listed below.

Table 22. Occurrence rate of Non-Serious and Serious Adverse Events through M12 visit – Safety Set (N=115)

|  Non-Serious Adverse Events | Subjects with Events (%)  |
| --- | --- |
|  Application site irritation | 28 (24.3%)  |
|  Dysphagia | 21 (18.3%)  |
|  Incision site swelling | 19 (16.5%)  |
|  Medical device discomfort | 17 (14.8%)  |
|  Glossodynia | 15 (13.0%)  |
|  Implant site hypoaesthesia | 7 (6.1%)  |
|  Procedural pain | 7 (6.1%)  |
|  Dysphonia | 6 (5.2%)  |
|  Oropharyngeal pain | 6 (5.2%)  |
|  Post procedural contusion | 6 (5.2%)  |
|  Tongue movement disturbance | 5 (4.3%)  |
|  Tongue exfoliation | 4 (3.5%)  |
|  Medical device pain | 4 (3.5%)  |
|  Application site reaction | 4 (3.5%)  |
|  Glossitis | 4 (3.5%)  |

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|  Non-Serious Adverse Events | Subjects with Events (%)  |
| --- | --- |
|  Cough | 3 (2.6%)  |
|  Odynophagia | 3 (2.6%)  |
|  Pain in jaw | 3 (2.6%)  |
|  Post procedural swelling | 3 (2.6%)  |
|  Speech disorder | 3 (2.6%)  |
|  Dry mouth | 2 (1.7%)  |
|  Dysarthria | 2 (1.7%)  |
|  Ear discomfort | 2 (1.7%)  |
|  Epistaxis | 2 (1.7%)  |
|  Headache | 2 (1.7%)  |
|  Hypoaesthesia oral | 2 (1.7%)  |
|  Implant site irritation | 2 (1.7%)  |
|  Incision site pain | 2 (1.7%)  |
|  Neck pain | 2 (1.7%)  |
|  Post procedural fever | 2 (1.7%)  |
|  Procedural headache | 2 (1.7%)  |
|  Procedural site reaction | 2 (1.7%)  |
|  Sleep disorder | 2 (1.7%)  |
|  Somnolence | 2 (1.7%)  |
|  Tinnitus | 2 (1.7%)  |
|  Tongue spasm | 2 (1.7%)  |
|  Ageusia | 1 (0.9%)  |
|  Anxiety | 1 (0.9%)  |
|  Application site infection | 1 (0.9%)  |
|  Application site rash | 1 (0.9%)  |
|  Application site ulcer | 1 (0.9%)  |
|  Atrial fibrillation | 1 (0.9%)  |
|  Back pain | 1 (0.9%)  |
|  Dermatitis contact | 1 (0.9%)  |
|  Dizziness | 1 (0.9%)  |
|  Dyspepsia | 1 (0.9%)  |
|  Ear pain | 1 (0.9%)  |
|  Fatigue | 1 (0.9%)  |
|  Foreign body | 1 (0.9%)  |
|  Gastroesophageal reflux disease | 1 (0.9%)  |
|  Hemorrhage | 1 (0.9%)  |
|  Hypoaesthesia | 1 (0.9%)  |
|  Implant site infection | 1 (…

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**Source:** [https://fda.innolitics.com/device/P240024](https://fda.innolitics.com/device/P240024)

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