Software as a Medical Device, Therapeutic, Pediatric
Indications for Use
The Omnipod 6 algorithm is intended for use with compatible integrated continuous glucose monitors (iCGM) and alternate controller enabled (ACE) pumps to automatically increase, decrease, and pause delivery of insulin based on current and predicted glucose values. The Omnipod 6 algorithm is intended for the management of type 1 diabetes mellitus in persons 2 years of age and older and type 2 diabetes mellitus in persons 18 years of age and older. The Omnipod 6 algorithm is intended for single patient use and requires a prescription.
Device Story
Software-only interoperable automated glycemic controller (iAGC); resides on Omnipod 6 Pod and App (smartphone/controller). Receives glucose data from compatible iCGM; calculates insulin micro-bolus outputs every 5 minutes based on 60-minute glucose prediction horizon; transmits commands to connected ACE pump. Operates in Automated Mode (closed-loop) or Manual Mode (open-loop). Automated Mode features: standard automated delivery based on user-set target (100–150 mg/dL); Limited Mode (during sensor warm-up or signal loss); Activity Feature (temporary 150 mg/dL target for exercise). Algorithm adapts to user insulin history and bolus behavior. Used in ambulatory settings by patients. Healthcare providers use output to manage glycemic control; patients benefit from automated insulin adjustments reducing manual intervention requirements.
Clinical Evidence
STRIVE randomized crossover study (n=132; 98 T1D, 34 T2D; ages 2-70). Compared Omnipod 6 vs. Omnipod 5. Primary endpoints: non-inferiority for time below 54 mg/dL, time below 70 mg/dL, time in range (70-180 mg/dL), and mean sensor glucose. Results: met all primary safety endpoints; no severe hypoglycemia, DKA, or HHS. Exploratory analysis showed improved glycemic metrics and non-inferiority in hypoglycemia during optional bolus phase (reduced manual boluses).
Technological Characteristics
Software-only iAGC; resides on Pod/App. Connectivity via Bluetooth Low Energy (BLE). Interoperable with iCGM and ACE pumps. Adaptive algorithm adjusts insulin based on user history and bolus behavior. Firmware updated via Over-the-Air (OTA) mechanism. Complies with IEC 62304 and ISO 14971.
Indications for Use
Indicated for management of type 1 diabetes in persons 2+ years old and type 2 diabetes in persons 18+ years old. Requires prescription for single patient use.
Regulatory Classification
Identification
An interoperable automated glycemic controller is a device intended to automatically calculate drug doses based on inputs such as glucose and other relevant physiological parameters, and to command the delivery of such drug doses from a connected infusion pump. Interoperable automated glycemic controllers are designed to reliably and securely communicate with digitally connected devices to allow drug delivery commands to be sent, received, executed, and confirmed. Interoperable automated glycemic controllers are intended to be used in conjunction with digitally connected devices for the purpose of maintaining glycemic control.
Special Controls
*Classification.* Class II (special controls). The special controls for this device are:(1) Design verification and validation must include:
(i) An appropriate, as determined by FDA, clinical implementation strategy, including data demonstrating appropriate, as determined by FDA, clinical performance of the device for its intended use, including all of its indications for use.
(A) The clinical data must be representative of the performance of the device in the intended use population and in clinically relevant use scenarios and sufficient to demonstrate appropriate, as determined by FDA, clinical performance of the device for its intended use, including all of its indications for use.
(B) For devices indicated for use with multiple therapeutic agents for the same therapeutic effect (
*e.g.,* more than one type of insulin), data demonstrating performance with each product or, alternatively, an appropriate, as determined by FDA, clinical justification for why such data are not needed.(C) When determined to be necessary by FDA, the strategy must include postmarket data collection to confirm safe real-world use and monitor for rare adverse events.
(ii) Results obtained through a human factors study that demonstrates that an intended user can safely use the device for its intended use.
(iii) A detailed and appropriate, as determined by FDA, strategy to ensure secure and reliable means of data transmission with other intended connected devices.
(iv) Specifications that are appropriate, as determined by FDA, for connected devices that shall be eligible to provide input to (
*e.g.,* specification of glucose sensor performance) or accept commands from (*e.g.,* specifications for drug infusion pump performance) the controller, and a detailed strategy for ensuring that connected devices meet these specifications.(v) Specifications for devices responsible for hosting the controller, and a detailed and appropriate, as determined by FDA, strategy for ensuring that the specifications are met by the hosting devices.
(vi) Documentation demonstrating that appropriate, as determined by FDA, measures are in place (
*e.g.,* validated device design features) to ensure that safe therapy is maintained when communication with digitally connected devices is interrupted, lost, or re-established after an interruption. Validation testing results must demonstrate that critical events that occur during a loss of communications (*e.g.,* commands, device malfunctions, occlusions, etc.) are handled and logged appropriately during and after the interruption to maintain patient safety.(vii) A detailed plan and procedure for assigning postmarket responsibilities including adverse event reporting, complaint handling, and investigations with the manufacturers of devices that are digitally connected to the controller.
(2) Design verification and validation documentation must include appropriate design inputs and design outputs that are essential for the proper functioning of the device that have been documented and include the following:
(i) Risk control measures to address device system hazards;
(ii) Design decisions related to how the risk control measures impact essential performance; and
(iii) A traceability analysis demonstrating that all hazards are adequately controlled and that all controls have been validated in the final device design.
(3) The device shall include appropriate, as determined by FDA, and validated interface specifications for digitally connected devices. These interface specifications shall, at a minimum, provide for the following:
(i) Secure authentication (pairing) to connected devices;
(ii) Secure, accurate, and reliable means of data transmission between the controller and connected devices;
(iii) Sharing of necessary state information between the controller and any connected devices (
*e.g.,* battery level, reservoir level, sensor use life, pump status, error conditions);(iv) Ensuring that the controller continues to operate safely when data is received in a manner outside the bounds of the parameters specified;
(v) A detailed process and procedures for sharing the controller's interface specification with connected devices and for validating the correct implementation of that protocol; and
(vi) A mechanism for updating the controller software, including any software that is required for operation of the controller in a manner that ensures its safety and performance.
(4) The device design must ensure that a record of critical events is stored and accessible for an adequate period to allow for auditing of communications between digitally connected devices, and to facilitate the sharing of pertinent information with the responsible parties for those connected devices. Critical events to be stored by the controller must, at a minimum, include:
(i) Commands issued by the controller, and associated confirmations the controller receives from digitally connected devices;
(ii) Malfunctions of the controller and malfunctions reported to the controller by digitally connected devices (
*e.g.,* infusion pump occlusion, glucose sensor shut down);(iii) Alarms and alerts and associated acknowledgements from the controller as well as those reported to the controller by digitally connected devices; and
(iv) Connectivity events (
*e.g.,* establishment or loss of communications).(5) The device must only receive glucose input from devices cleared under § 862.1355 (integrated continuous glucose monitoring system), unless FDA determines an alternate type of glucose input device is designed appropriately to allow the controller to meet the special controls contained within this section.
(6) The device must only command drug delivery from devices cleared under § 880.5730 of this chapter (alternate controller enabled infusion pump), unless FDA determines an alternate type of drug infusion pump device is designed appropriately to allow the controller to meet the special controls contained within this section.
(7) An appropriate, as determined by FDA, training plan must be established for users and healthcare providers to assure the safety and performance of the device when used. This may include, but not be limited to, training on device contraindications, situations in which the device should not be used, notable differences in device functionality or features compared to similar alternative therapies, and information to help prescribers identify suitable candidate patients, as applicable.
(8) The labeling required under § 809.10(b) of this chapter must include:
(i) A contraindication for use in pediatric populations except to the extent clinical performance data or other available information demonstrates that it can be safely used in pediatric populations in whole or in part.
(ii) A prominent statement identifying any populations for which use of this device has been determined to be unsafe.
(iii) A prominent statement identifying by name the therapeutic agents that are compatible with the controller, including their identity and concentration, as appropriate.
(iv) The identity of those digitally connected devices with which the controller can be used, including descriptions of the specific system configurations that can be used, per the detailed strategy submitted under paragraph (b)(1)(iii) of this section.
(v) A comprehensive description of representative clinical performance in the hands of the intended user, including information specific to use in the pediatric use population, as appropriate.
(vi) A comprehensive description of safety of the device, including, for example, the incidence of severe hypoglycemia, diabetic ketoacidosis, and other relevant adverse events observed in a study conducted to satisfy paragraph (b)(1)(i) of this section.
(vii) For wireless connection enabled devices, a description of the wireless quality of service required for proper use of the device.
(viii) For any controller with hardware components intended for multiple patient reuse, instructions for safely reprocessing the hardware components between uses.
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**FDA** U.S. FOOD & DRUG
ADMINISTRATION
## 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY
### I Background Information:
#### A 510(k) Number
K261461
#### B Applicant
Insulet Corporation
#### C Proprietary and Established Names
Omnipod 6 algorithm
#### D Regulatory Information
| Product Code(s) | Classification | Regulation Section | Panel |
| --- | --- | --- | --- |
| QJI | Class II | 21 CFR 862.1356 | CH – Clinical Chemistry |
#### E Purpose for Submission:
New device.
### II Intended Use/Indications for Use:
#### A Intended Use(s):
See Indications for Use below.
#### B Indication(s) for Use:
The Omnipod 6 algorithm is intended for use with compatible integrated continuous glucose monitors (iCGM) and alternate controller enabled (ACE) pumps to automatically increase, decrease, and pause delivery of insulin based on current and predicted glucose values.
The Omnipod 6 algorithm is intended for the management of type 1 diabetes mellitus in persons 2 years of age and older and type 2 diabetes mellitus in persons 18 years of age and older.
The Omnipod 6 algorithm is intended for single patient use and requires a prescription.
Food and Drug Administration
10903 New Hampshire Avenue
Silver Spring, MD 20993-0002
www.fda.gov
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## C Special Conditions for Use Statement(s):
### Rx – For Prescription Use Only
- • DO NOT use the Omnipod 6 algorithm in pregnant women, critically ill patients, and those on dialysis. The safety of the Omnipod 6 algorithm has not been evaluated in these populations. Consult with your healthcare provider if any of these conditions apply to you before using the Omnipod 6 algorithm.
- • The Omnipod 6 algorithm should NOT be used by anyone under the age of 2 years old. The Omnipod 6 algorithm should also NOT be used in people who require less than 5 units of insulin per day as the safety of the technology has not been evaluated in this population.
- • DO NOT use the Omnipod 6 System if you do not have adequate vision and/or hearing to recognize all functions of the Omnipod 6 System including alerts, alarms, and reminders according to instructions.
- • Do NOT use Omnipod 6 System with a Dexcom sensor if you are taking hydroxyurea, a medication used in the treatment of diseases including cancer and sickle cell anemia. Your Dexcom sensor readings could be falsely elevated and could result in over-delivery of insulin which can lead to severe hypoglycemia.
- • DO NOT use the Omnipod 6 System with the Libre 2 Plus or Libre 3 Plus sensor if you are taking more than 1000 mg of ascorbic acid (Vitamin C) per day, a substance found in supplements like multivitamins or cold remedies such as Airborne and Emergen-C. Taking more than 1000 mg of Vitamin C per day may falsely raise your sensor readings and result in over-delivery of insulin that could result in severe hypoglycemia.
- • DO NOT use the Omnipod 6 System in oxygen rich environments (greater than 25% oxygen), which include home or surgical areas that use supplementary oxygen and hyperbaric chambers. Hyperbaric, or high pressure, chambers are sometimes used to promote healing of diabetic ulcers, or to treat carbon monoxide poisoning, certain bone and tissue infections, and decompression sickness. Exposure to oxygen rich environments could result in combustion of the Pod or Omnipod 6 Controller, which can cause severe burns to the body.
- • DO NOT use the Omnipod 6 System at low atmospheric pressure (below 700 hPA). You could encounter such low atmospheric pressures at high elevations, such as when mountain climbing or living at elevations above 10,000 feet (3,000 meters). Change in atmospheric pressure can also occur during take-off with air travel. Unintended insulin delivery can occur if there is expansion of tiny air bubbles that may exist inside the Pod. This can result in hypoglycemia. It is important to check your glucose frequently when flying to avoid prolonged hypoglycemia.
- • DO NOT use the Omnipod 6 System in high atmospheric pressure environments (above 1060 hPA), which can be found in a hyperbaric chamber. Hyperbaric, or high pressure, chambers, are sometimes used to promote healing of diabetic ulcers, or to treat carbon monoxide poisoning, certain bone and tissue infections, and decompression sickness. Exposure to high atmospheric pressure environments can damage your Pod and Omnipod 6 Controller which could result in under-delivery of insulin which can lead to hyperglycemia.
- • ALWAYS remove and dispose of the Pod before X-ray, Magnetic Resonance Imaging (MRI), or Computed Tomography (CT) scan (or any similar test or procedure). In addition, place the Controller or smartphone outside of the procedure room. Exposure to X-ray, MRI, or CT
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treatment can damage these components. Check with your healthcare provider for Pod removal guidelines.
- DO NOT expose any Omnipod 6 System products or supplies to extreme temperatures as this results in them not functioning properly. Store all Omnipod 6 System products and supplies, including unopened Pods, in a cool, dry place.
### III Device Description
The candidate device is the Omnipod 6 algorithm, a software-only component of the Omnipod 6 Automated Insulin Delivery (AID) System that includes the following devices as well:
- Omnipod 6 ACE Pump that is identical to the Omnipod 5 ACE Pump.
- SmartBolus Calculator that is identical to the one used in the Omnipod 5 Automated Insulin Delivery (AID) System.
- Third-party iCGM (cleared for use with Dexcom G6 and G7, and Abbott Freestyle Libre 2)
The Omnipod 6 System is a hybrid closed loop system and can operate in Manual Mode (Omnipod 6 algorithm is not enabled) and Automated Mode (Omnipod 6 algorithm is enabled). Automated Mode operation requires connected iCGM, and the algorithm adjusts insulin delivery through micro-boluses, based on Estimated Glucose Values (EGV) from the iCGM and past insulin delivery history. Automated Mode has three states of operation:
1. Fully Automated: In fully Automated mode, the Algorithm calculates and adjusts insulin delivery based on several factors including the user's set target glucose (100-150 mg/dL), total daily insulin (TDI), and sensor glucose values.
2. Automated: Limited (Limited Mode): Enabled when the iAGC is not receiving data from a connected iCGM for 20 minutes or more or during sensor warm up. While in Limited Mode, the user will receive basal insulin at or below either the pre-programmed basal rate or the rate based on past insulin usage, whichever is less. Once the iAGC and iCGM are back into range and a valid EGV is received from the iCGM, the system will resume delivery of insulin in fully Automated mode.
3. Activity: Intended for use during periods when insulin sensitivity is expected to be higher, such as during exercise. The feature can be set for various time durations during Automated mode. With Activity, the algorithm reduces insulin delivery by setting a temporary glucose target to 150 mg/dL. Activity has a maximum selectable duration of 24 hours.
### IV Substantial Equivalence Information:
#### A Predicate Device Name(s):
Omnipod 5 algorithm
#### B Predicate 510(k) Number(s):
K251779
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# **C Comparison with Predicate(s):**
| **Device & Predicate Device(s):** | K261461 | K251779 |
| --- | --- | --- |
| Device Trade Name | Omnipod 6 algorithm | Omnipod 5 algorithm |
| **General Device Characteristic Similarities** | | |
| Intended Use/Indications For Use | Intended for use with compatible integrated continuous glucose monitors (iCGM) and alternate controller enabled (ACE) pumps to automatically increase, decrease, and pause delivery of insulin based on current and predicted glucose values. Intended for the management of type 1 diabetes mellitus in persons 2 years of age and older and type 2 diabetes mellitus in persons 18 years of age and older. Intended for single patient use and requires a prescription. | Same |
| Compatible Insulin | NovoLog, Humalog, Admelog, and Kirsty U-100 insulins | Same |
| Target Glucose Control Range | 100-150 mg/dl, user-customizable | Same |
| **General Device Characteristic Differences** | | |
| Adaptive rate | Automatically adjusted adaptive rate personalized to user's insulin history and bolus behavior | Adaptive rate that automatically adjusts to user's insulin history |
# **V Standards/Guidance Documents Referenced:**
- ANSI AAMI ISO 14971:2019, Medical devices – Applications of risk management to medical devices
- ANSI AAMI IEC 62304:2006/A1:2016, Medical device software – Software life cycle processes
- ISO 14155 Third edition 2020-07, Clinical investigation of medical devices for human subjects – Good clinical practice
- ISO 20417 First edition 2021-04 Corrected version 2021-12, Medical devices – Information to be supplied by the manufacturer
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## VI Performance Characteristics:
### A. Non-Clinical Performance
Non-clinical performance is leveraged from the predicate submission.
### B. Clinical Studies:
#### Summary of Clinical Testing
A randomized crossover pivotal study was conducted to evaluate safety and efficacy of the Omnipod 6 algorithm by comparing the Omnipod 6 System (formerly called Omnipod 5 SmartAdjust 2.0, or OP5SA2.0, or OP5SA) with the Omnipod 5 System (OP5) in individuals with type 1 or type 2 diabetes. A summary of the pivotal clinical study is provided in the following table:
| Study Feature | Description |
| --- | --- |
| Title | Safety and Efficacy of the Omnipod 5 SmartAdjust 2.0 System Compared to the Omnipod 5 System in Individuals with Type 1 and Type 2 Diabetes (STRIVE) |
| Study Design | A multi-center, randomized two-sequence crossover study (Periods 1 and 2) designed to compare the Omnipod 5 SA 2.0 System at a target of 100 mg/dL (OP5SA100 treatment group) to the commercially available Omnipod 5 System at a target of 110 mg/dL (OP5110 treatment group). All participants who completed Periods 1 and 2 continued to the Restricted Bolus phase (Period 3), during which all participants used the Omnipod 5 SA 2.0 System at a target of 100 mg/dL with a goal of no more than 3 insulin boluses per day. |
| Investigational Device | Omnipod 6 (or OP5SA) System: modified version of OP5 Pod (updated software - Omnipod 6 algorithm Pod), modified version of the US OP5 app on a compatible Smartphone/Controller (Omnipod 6 App), and Dexcom G6 CGM. The OP5 System: OP5 Pod (commercial product), OP5 App (installed on the Insulet-provided commercially equivalent Controller or smartphone), and Dexcom G6 CGM. |
| Investigational Sites | Eleven (11) sites in the United States enrolled participants. |
| Study Population | - Type 1 Diabetes: diagnosed with type 1 diabetes for at least 3 months for participants aged 2 to < 7 years and at least 1 year for participants aged 7 to 70 years OR - Type 2 Diabetes: diagnosed with type 2 diabetes for at least 1 year for participants aged 18 to 70 years |
| Protocol Overview | During Period 1, study participants were randomly assigned to either the OP5SA100 or the OP5110 treatment groups and commenced Period 1 for 4 weeks. Following Period 1, participants crossed over to the other treatment group and |
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| Study Feature | Description |
| --- | --- |
| | commenced Period 2 for 4 weeks. All participants continued to the Restricted Bolus phase (Period 3), during which all participants used the Omnipod 5 SA 2.0 System at a target of 100 mg/dL for an additional 4 to 6 weeks (depending on age group) with a goal of no more than 3 boluses per day. |
| Periods 1 and 2 (Crossover Phase) Endpoints | Primary Safety Endpoints The following primary safety endpoints were tested hierarchically for non-inferiority between the two treatment groups: - Percentage of time < 54 mg/dL (non-inferiority (NI) margin of 0.75%) - Percentage of time < 70 mg/dL (NI margin of 3.0%) - Percentage of time in range 70 – 180 mg/dL (NI margin of 3.0%) - Mean sensor glucose (NI margin of 8.0 mg/dL) Additional Safety Endpoints The following additional safety endpoints were tested for the Crossover phase (Periods 1 and 2): - Number of severe hypoglycemia (SH) events - Number of diabetic ketoacidosis (DKA) or hyperosmolar hyperglycemic state (HHS) events Exploratory Endpoints The following exploratory endpoints were tested for superiority between the two treatment groups except for total boluses per day, percentage total insulin as basal, and total daily insulin per kg: - Percentage of time in range 70 –180 mg/dL - Mean sensor glucose - Percentage of time > 180 mg/dL - Percentage of time > 250 mg/dL - Percentage of time > 300 mg/dL - Percentage of time in range 70 –140 mg/dL - Total boluses per day (no formal testing) - Percentage total insulin as basal (no formal testing) - Total daily insulin per kg (no formal testing) |
| Period 3 (Restricted Bolus Phase) Endpoints | Safety Endpoints The following safety endpoints were tested for non-inferiority for the Restricted Bolus phase (Period 3) versus the treatment groups from the Crossover phase (Periods 1 and 2): - Percentage of time < 54 mg/dL (NI margin of 0.75%) - Percentage of time < 70 mg/dL (NI margin of 3.0%) Additional Safety Endpoints The following additional safety endpoints were tested for the Restricted Bolus phase (Period 3): - Number of SH events |
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| Study Feature | Description |
| --- | --- |
| | - Number of DKA or HHS eventsExploratory Endpoints The following exploratory endpoints were tested for superiority, except for total boluses per day, percentage total insulin as basal, and total daily insulin per kg, for Period 3 compared with the two treatment groups from Periods 1 and 2: - Percentage of time in range 70 –180 mg/dL - Mean sensor glucose - Percentage of time > 180 mg/dL - Percentage of time > 250 mg/dL - Percentage of time > 300 mg/dL - Percentage of time in range 70 –140 mg/dL - Total boluses per day (no formal testing) - Percentage total insulin as basal (no formal testing) Total daily insulin per kg (no formal testing) |
| Breakdown of subjects | - 136 participants were screened - 132 were randomized and started Period 1; 131 completed Period 1 (1 T1D 3 yrs dropped during Period 1) - 131 started Period 2 and 130 completed Period 2 (1 T1D 16 yrs was unable to complete visits, but had sufficient data for crossover analysis) - 128 started and completed Period 3 (1 T1D 2 yrs and 1 T1D 16 yrs dropped before Period 3) |
| Safety Results | There were no reports of SH, DKA or HHS, and there were also no deaths, unanticipated adverse device effects, serious adverse device effects or serious adverse events during the Crossover phase and during the Restricted Bolus phase. |
# Participant Demographics (N = 132 subjects at Randomization)
| | T1D (N=98) | T2D (N=34) | Overall (N=132) |
| --- | --- | --- | --- |
| **Age (yrs) - n (%)** | | | |
| 2-<6 | 29 (30%) | 0 | 29 (22%) |
| 6-<14 | 36 (37%) | 0 | 36 (27%) |
| 14-<22 | 6 (6%) | 0 | 6 (5%) |
| 22 and over | 27 (28%) | 34 (100%) | 61 (46%) |
| Mean (SD) | 19 (18) | 56 (9) | 28 (23) |
| Range | 2 to 67 | 23 to 70 | 2 to 70 |
| **Sex – Female – n (%)** | 57 (58%) | 20 (59%) | 77 (58%) |
| **Weight (kg) - Mean (SD)** | 50 (27) | 101 (32) | 63 (36) |
| **BMI – n (%)** | | | |
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| | T1D (N=98) | T2D (N=34) | Overall (N=132) |
| --- | --- | --- | --- |
| <18.5 | 38 (39%) | 0 | 38 (29%) |
| 18.5-<25 | 34 (35%) | 4 (12%) | 38 (29%) |
| 25-<30 | 15 (15%) | 9 (26%) | 24 (18%) |
| ≥30 | 11 (11%) | 21 (62%) | 32 (24%) |
| Mean (SD) (kg/m^{2}) | 22 (6) | 35 (10) | 25 (9) |
| Range (kg/m^{2}) | 15 to 44 | 21 to 72 | 15 to 72 |
| **Race – n (%) or n** | | | |
| American Indian/Alaskan Native | 0 | 0 | 0 |
| Asian | 0 | 0 | 0 |
| Black/African-American | 6 (6%) | 6 (18%) | 12 (9%) |
| More than one race | 4 (4%) | 1 (3%) | 5 (4%) |
| Native Hawaiian/Other Pacific Islander | 0 | 0 | 0 |
| White | 86 (88%) | 27 (79%) | 113 (86%) |
| Unknown/ not reported | 2 (2%) | 0 | 2 (2%) |
| **Ethnicity – n (%)** | | | |
| Hispanic | 8 (8%) | 13 (38%) | 21 (16%) |
| Non-Hispanic | 90 (92%) | 20 (59%) | 110 (83%) |
| Unknown/not reported | 0 | 1 (3%) | 1 (<1%) |
| **Race/Ethnicity – n (%)** | | | |
| White non-Hispanic | 79 (81%) | 14 (41%) | 93 (70%) |
| Black non-Hispanic | 6 (6%) | 5 (15%) | 11 (8%) |
| Hispanic | 8 (8%) | 13 (38%) | 21 (16%) |
| Other races and ethnicities | 5 (5%) | 2 (6%) | 7 (5%) |
| **Education – n (%)** | | | |
| High school / GED or less | 21 (21%) | 14 (41%) | 35 (27%) |
| Technical/vocational/associate | 10 (10%) | 8 (24%) | 18 (14%) |
| College Graduate (Bachelor's or equiv.) | 29 (30%) | 6 (18%) | 35 (27%) |
| Advanced Degree | 37 (38%) | 4 (12%) | 41 (31%) |
| Do not wish to provide/NA | 1 (1%) | 2 (6%) | 3 (2%) |
| **Annual Household Income – n (%)** | | | |
| <$50,000/year | 5 (5%) | 10 (29%) | 15 (11%) |
| $50,000-<$100,000/year | 11 (11%) | 7 (21%) | 18 (14%) |
| $100,000-<$200,000/year | 37 (38%) | 10 (29%) | 47 (36%) |
| ≥$200,000/year | 35 (36%) | 4 (12%) | 39 (30%) |
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| | **T1D (N=98)** | **T2D (N=34)** | **Overall (N=132)** |
| --- | --- | --- | --- |
| Unknown/NA | 10 (10%) | 3 (9%) | 13 (10%) |
| **Health Insurance – n (%)** | | | |
| Private | 85 (87%) | 22 (65%) | 107 (81%) |
| Other | 13 (13%) | 12 (35%) | 25 (19%) |
* For participants <18yrs, this is referring to parental education.
# Participant Characteristics – Diabetes by Type and Age (N = 132 subjects at Randomization)
| | **T1D (N=98)** | **T2D (N=34)** | **Overall (N=132)** |
| --- | --- | --- | --- |
| **Diabetes Duration - n (%)** | | | |
| <5yrs | 45 (46%) | 1 (3%) | 46 (35%) |
| 5-<10 yrs | 25 (26%) | 2 (6%) | 27 (20%) |
| 10-<20 yrs | 11 (11%) | 13 (38%) | 24 (18%) |
| ≥20 yrs | 17 (17%) | 18 (53%) | 35 (27%) |
| Median (IQR) - yrs | 6 (3, 13) | 21 (14, 25) | 9 (3, 22) |
| Range - yr | 1 to 61 | 4 to 33 | 1 to 61 |
| **Non-Insulin Medications - n (%)** | | | |
| GLP1 | 6 (6%) | 23 (68%) | 29 (22%) |
| SGLT2 | 0 | 14 (41%) | 14 (11%) |
| Metformin | 1 (1%) | 22 (65%) | 23 (17%) |
| Both GLP1 and SGLT2 | 0 | 10 (29%) | 10 (8%) |
| GLP1 only | 6 (6%) | 13 (38%) | 19 (14%) |
| SGLT2 only | 0 | 4 (12%) | 4 (3%) |
| None | 92 (94%) | 7 (21%) | 99 (75%) |
| **Duration of Omnipod Use at Baseline - n (%)** | | | |
| 3-<6 months | 5 (5%) | 3 (9%) | 8 (6%) |
| 6 months-<1 year | 11 (11%) | 4 (12%) | 15 (11%) |
| 1-<2 years | 22 (22%) | 18 (53%) | 40 (30%) |
| 2-<5 years | 53 (54%) | 7 (21%) | 60 (45%) |
| >= 5 years | 7 (7%) | 2 (6%) | 9 (7%) |
| **HbA1c - Local - n (%)** | | | |
| <8.0% | 87 (89%) | 26 (76%) | 113 (86%) |
| 8.0%-<9.0% | 10 (10%) | 7 (21%) | 17 (13%) |
| ≥9.0% | 1 (1%) | 1 (3%) | 2 (2%) |
| Mean (SD) - % | 6.9 (0.8) | 7.3 (0.8) | 7.0 (0.8) |
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| | T1D (N=98) | T2D (N=34) | Overall (N=132) |
| --- | --- | --- | --- |
| Range - % | 4.9 to 9.2 | 5.5 to 9.4 | 4.9 to 9.4 |
| **Total Daily Insulin (U/kg/day)** | | | |
| Mean (SD) | 0.8 (0.3) | 0.6 (0.2) | 0.7 (0.3) |
| Range | 0.1 to 1.7 | 0.2 to 1.1 | 0.1 to 1.7 |
| **Total Daily Insulin (U/day)** | | | |
| Mean (SD) | 39 (27) | 58 (28) | 44 (28) |
| Range | 9 to 147 | 18 to 123 | 9 to 147 |
| **SH ever - n (%)** | 14 (14%) | 4 (12%) | 18 (14%) |
| **DKA ever - n (%)** | 32 (33%) | 0 | 32 (24%) |
| **HHS ever - n (%)** | 0 | 0 | 0 |
### Crossover Phase Results
The primary safety endpoints in the crossover phase were tested hierarchically for non-inferiority between the two treatment groups (OP5SA100 versus OP5110) during the Crossover phase (Periods 1 and 2). The non-inferiority results are summarized below: pooled results across diabetes type and age, percentage of time < 54 mg/dL by diabetes type and age, and percentage of time < 70 mg/dL by diabetes type and age.
### Primary Safety Endpoints: Non-inferiority Pooled Across Diabetes Type and Age
| | Baseline (N=132) | OP5110 (N=132) | OP5SA100 (N=131) | Mean Estimate and 95% CI for OP5SA100 vs. OP5110 | NI | P-Value for NI OP5SA100 vs. OP5110*§ |
| --- | --- | --- | --- | --- | --- | --- |
| **Non-inferiority in % below 54 mg/dL (NI=0.75%) - mean (SD)^** | 0.29% (0.31%) | 0.30% (0.30%) | 0.34% (0.30%) | 0.04% (-∞, 0.11%) | 0.75% | <0.001 |
| **Non-inferiority in % below 70 mg/dL (NI=3.0%) - mean (SD)^** | 1.60% (1.37%) | 1.66% (1.30%) | 2.02% (1.47%) | 0.37% (-∞, 0.56%) | 3.0% | <0.001 |
| **Non-inferiority in % in range 70-180 mg/dL (NI=3.0%) - mean (SD)** | 66% (15%) | 70% (13%) | 73% (12%) | 2.9% (1.9%, +∞) | -3.0% | <0.001 |
| **Non-inferiority in mean sensor glucose (NI=8 mg/dL) - mean (SD)** | 165 (27) | 158 (20) | 151 (18) | -7 (-∞, -6) | 8 mg/dL | <0.001 |
*P-values tested hierarchically, and the process stopped at the first P-value ≥0.05. A repeated measures linear regression that controlled for period effect and accounted for the baseline values was used.
^Winsorized Mean and SD; values below 10th and above 90th percentiles were winsorized.
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SA test for carry-over effect was done and it was not statistically significant for any of the four primary safety endpoints. Additionally, treatment group interactions with type and age were done for percentage time below 54 and 70 mg/dL and none were statistically significant.
# **Primary Safety Endpoint: Non-inferiority in Percentage of Time Below 54 mg/dL (NI = 0.75%) by Diabetes Type and Age**
| | Baseline mean (SD)^ (N=132) | OP5110 mean (SD)^ (N=132) | OP5SA100 mean (SD)^ (N=131) |
| --- | --- | --- | --- |
| **P-value for Treatment Group Interaction with Type = 0.30** | | | |
| Type 1 | 0.35% (0.31%) | 0.38% (0.30%) | 0.40% (0.30%) |
| Type 2 | 0.14% (0.24%) | 0.08% (0.12%) | 0.15% (0.21%) |
| **Type 1 Only: P-value for Treatment Group Interaction with Age = 0.48** | | | |
| Age 2-<6 yrs | 0.42% (0.35%) | 0.47% (0.34%) | 0.48% (0.32%) |
| Age 6-<14 yrs | 0.33% (0.27%) | 0.36% (0.26%) | 0.41% (0.30%) |
| Age ≥14 yrs | 0.22% (0.29%) | 0.20% (0.26%) | 0.25% (0.25%) |
| **P-value for Treatment Group Interaction with Age (14-<22 vs. ≥22-70) = 0.75** | | | |
| Age 14-<22 yrs | 0.30% (0.29%) | 0.23% (0.12%) | 0.29% (0.22%) |
| Age ≥22-70 yrs | 0.21% (0.27%) | 0.19% (0.25%) | 0.22% (0.22%) |
^Winsorized Mean and SD
# **Primary Safety Endpoint: Non-inferiority in Percentage of Time Below 70 mg/dL (NI=3.0%) by Diabetes Type and Age**
| | Baseline mean (SD)^ (N=132) | OP5110 mean (SD)^ (N=132) | OP5SA100 mean (SD)^ (N=131) |
| --- | --- | --- | --- |
| **P-value for Treatment Group Interaction with Type = 0.21** | | | |
| Type 1 | 1.97% (1.35%) | 2.09% (1.22%) | 2.50% (1.35%) |
| Type 2 | 0.55% (0.77%) | 0.42% (0.47%) | 0.65% (0.77%) |
| **Type 1 only: P-value for Treatment Group Interaction with Age = 0.28** | | | |
| Age 2-<6 yrs | 2.27% (1.41%) | 2.45% (1.30%) | 2.78% (1.34%) |
| Age 6-<14 yrs | 2.07% (1.35%) | 2.01% (1.14%) | 2.67% (1.40%) |
| Age ≥14 yrs | 1.06% (1.15%) | 1.13% (1.15%) | 1.34% (1.24%) |
| **P-value for Treatment Group Interaction with Age (14-<22 vs. ≥22-70) = 0.82** | | | |
| Age 14-<22 yrs | 1.28% (1.07%) | 1.56% (0.55%) | 1.55% (0.7%) |
| Age ≥22-70 yrs | 0.92% (0.91%) | 1.00% (1.01%) | 1.25% (1.16%) |
^Winsorized Mean and SD
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### Restricted Bolus Phase Results
The Table below presents the non-inferiority analysis of the 2 safety endpoints for the Restricted Bolus phase (Period 3) compared with the OP5110 group from the Crossover phase (Periods 1 and 2).
#### Safety Endpoints for Restricted Bolus Phase (Period 3)
| | Baseline (N=132) | OP5110 (N=132) | OP5SA100 (N=131) | Restricted Bolus (N=128) | Mean Estimate and 95% CI for Restricted Bolus vs. OP5110 | NI | P-Value for NI Restricted Bolus vs. OP5110* |
| --- | --- | --- | --- | --- | --- | --- | --- |
| **Non-inferiority in % below 54 mg/dL (NI=0.75%) - mean (SD)^** | 0.29% (0.31%) | 0.30% (0.30%) | 0.34% (0.30%) | 0.41% (0.39%) | 0.11% (-∞, 0.18%) | 0.75% | <0.001 |
| **Non-inferiority in % below 70 mg/dL (NI=3.0%) - mean (SD)^** | 1.60% (1.37%) | 1.66% (1.30%) | 2.02% (1.47%) | 2.08% (1.50%) | 0.44% (-∞, 0.65%) | 3.0% | <0.001 |
*P-values tested hierarchically, and the process stops at the first P-value ≥0.05. A repeated measures linear regression that control for period effect and accounts for the baseline values was used.
^Winsorized Mean and SD; values below 10th and above 90th percentiles were winsorized.
#### Split factor during the restricted bolus phase (period 3):
- 71/128 users (55.4%) used the device with a time-weighted average split factor between 50-60%,
- 38/128 users (29.7%) used the device with a time-weighted average split factor between 60-70%,
- 19/128 users (14.8%) used the device with a time-weighted average split factor between 70-75%,
- 40/128 users (31.3%) utilized at least one pod with a split factor over 70%,
- 21/128 users (16.4%) reached the maximum split factor of 75% at least once over the last 3 pod wears (~9 days).
### C. Other Supportive Device Performance Characteristics Data
#### Software
Information on software of the device was reviewed and found to be acceptable. Software Verification and Validation activities were performed in accordance with IEC 62304 and FDA's guidance "General Principles of Software Validation." Software documentation was provided in accordance with FDA guidance "Content of Premarket Submissions for Device Software Functions".
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# **VII Proposed Labeling:**
The labeling supports the finding of substantial equivalence for this device.
# **VIII Conclusion:**
The submitted information in this premarket notification is complete and supports a substantial equivalence decision.
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