← Product Code [QFT](/submissions/OB/subpart-f%E2%80%94neurological-therapeutic-devices/QFT) · K231337 # EndeavorRx (K231337) _Akili Interactive Labs, Inc. · QFT · Dec 13, 2023 · Obstetrics/Gynecology · SESE_ **Canonical URL:** https://fda.innolitics.com/submissions/NE/subpart-f%E2%80%94neurological-therapeutic-devices/QFT/K231337 ## Device Facts - **Applicant:** Akili Interactive Labs, Inc. - **Product Code:** [QFT](/submissions/OB/subpart-f%E2%80%94neurological-therapeutic-devices/QFT.md) - **Decision Date:** Dec 13, 2023 - **Decision:** SESE - **Submission Type:** Traditional - **Regulation:** 21 CFR 882.5803 - **Device Class:** Class 2 - **Review Panel:** Obstetrics/Gynecology - **Attributes:** Software as a Medical Device, Therapeutic, Pediatric ## Indications for Use EndeavorRx is a digital therapeutic indicated to improve attention as measured by computer-based testing in children ages 8-17 years old with primarily inattentive or combined-type ADHD, who have demonstrated attention issue. Patients who engage with EndeavorRx demonstrate improvements in a digitally assessed measure Tests of Variables of Attention (TOVA) of sustained and selective attention and may not display benefits in typical behavioral symptoms, such as hyperactivity. EndeavorRx should be considered for use as part of a therapeutic program that may include: cliniciandirected therapy, medication, and/ or educational programs, which further address symptoms of the disorder. ## Device Story EndeavorRx is a prescription-only digital therapeutic (SaMD) for home use by pediatric patients (8-17 years) with ADHD. It functions as a video game delivered via mobile device, utilizing art, music, and reward cycles to engage patients. Input data includes device tilt (accelerometer) for steering and touch screen taps for targeting. The device employs a proprietary 'Selective Stimulus Management Engine' (SSME™) algorithm—a closed-loop system that automatically adjusts game difficulty based on individual performance to continuously challenge the user. Output consists of visual and auditory game stimuli. Healthcare providers use the device as part of a broader therapeutic program (e.g., with medication or behavioral therapy). The device aims to improve sustained and selective attention, as measured by the Test of Variables of Attention (TOVA). ## Clinical Evidence Clinical evidence includes a multi-center, open-label study of 162 adolescents (13-17 years). Primary endpoint: change from baseline in TOVA-ACS after 4 weeks. Efficacy population (N=146) showed significant mean improvement of 2.639 (95% CI: 2.018, 3.261; P < 0.0001). Safety profile was favorable with 2.5% experiencing mild/moderate treatment-emergent adverse events (frustration tolerance, headache); no serious adverse events reported. Results support safety and efficacy in the expanded age range. ## Technological Characteristics Digital therapeutic software (SaMD) for mobile platforms (iOS/Android). Employs adaptive 'Selective Stimulus Management Engine' (SSME™) algorithm. Closed-loop system adjusts difficulty based on user performance. Complies with ISO 14971 (risk management), IEC 62304 (software lifecycle), and IEC 82304 (health software safety). ## Regulatory Identification A digital therapy device for Attention Deficit Hyperactivity Disorder (ADHD) is a software intended to provide therapy for ADHD or any of its individual symptoms as an adjunct to clinician supervised treatment. ## Special Controls In combination with the general controls of the FD&C Act, the digital therapy device for Attention Deficit Hyperactivity Disorder is subject to the following special controls: *Classification.* Class II (special controls). The special controls for this device are:(1) Clinical performance testing must demonstrate and document the following under the labeled conditions for use, which include considerations for the ability of the device to: (i) Use a validated measure to evaluate effectiveness of device to provide therapy for ADHD or any of its individual symptoms; and (ii) Capture all adverse events. (2) Software must be described and provided in a clear and detailed manner to include all features and functions of the software implementing the digital therapy. Software verification, validation, and hazard analysis must also be provided. (3) The labeling must include the following items: (i) Patient and physician labeling must include instructions for use, including images that demonstrate how to interact with the device; (ii) Patient and physician labeling must list the minimum operating system (OS) requirements that support the software of the device; (iii) Patient and physician labeling must include a warning that the digital therapy device is not intended for use as a standalone therapeutic device; (iv) Patient and physician labeling must include a warning that the digital therapy device does not represent a substitution for the patient's medication; and (v) Physician labeling must include a summary of the clinical performance testing conducted with the device. ## Predicate Devices - EndeavorRx ([DEN200026](/device/DEN200026.md)) ## Submission Summary (Full Text) > This content was OCRed from public FDA records by [Innolitics](https://innolitics.com). If you use, quote, summarize, crawl, or train on this content, cite Innolitics at https://innolitics.com. > > Innolitics is a medical-device software consultancy. We help companies design, build, and clear FDA-regulated software and AI/ML devices, including [a 510(k)](https://innolitics.com/services/510ks/), [a De Novo](https://innolitics.com/services/regulatory/), [a SaMD](https://innolitics.com/services/end-to-end-samd/), [an AI/ML medical device](https://innolitics.com/services/medical-imaging-ai-development/), or [an FDA regulatory strategy](https://innolitics.com/services/regulatory/). {0}------------------------------------------------ Image /page/0/Picture/0 description: The image shows the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, with the letters "FDA" in a blue square. To the right of the blue square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue. December 13, 2023 Akili Interactive Labs, Inc. Bhupinder Singh Head of Quality and Regulatory Affairs 22 Boston Wharf Road 7th Floor Boston, MA 02210 Re: K231337 Trade/Device Name: EndeavorRx Regulation Number: 21 CFR 882.5803 Regulation Name: Digital therapy device for attention deficit hyperactivity disorder Regulatory Class: Class II Product Code: OFT Dated: November 13, 2023 Received: November 13, 2023 Dear Bhupinder Singh: We have reviewed your section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (the Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database available at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading. If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register. {1}------------------------------------------------ Additional information about changes that may require a new premarket notification are provided in the FDA guidance documents entitled "Deciding When to Submit a 510(k) for a Change to an Existing Device" (https://www.fda.gov/media/99812/download) and "Deciding When to Submit a 510(k) for a Software Change to an Existing Device" (https://www.fda.gov/media/99785/download). Your device is also subject to, among other requirements, the Quality System (QS) regulation (21 CFR Part 820), which includes, but is not limited to, 21 CFR 820.30. Design controls; 21 CFR 820.90. Nonconforming product; and 21 CFR 820.100, Corrective and preventive action. Please note that regardless of whether a change requires premarket review, the QS regulation requires device manufacturers to review and approve changes to device design and production (21 CFR 820.30 and 21 CFR 820.70) and document changes and approvals in the device master record (21 CFR 820.181). Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801); medical device reporting of medical device-related adverse events) (21 CFR Part 803) for devices or postmarketing safety reporting (21 CFR Part 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR Part 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR Parts 1000-1050. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems. For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100). {2}------------------------------------------------ Sincerely, # Robert Kang -S for Pamela Scott, MS Assistant Director DHT5B: Division of Neuromodulation and Rehabilitation Devices OHT5: Office of Neurological and Physical Medicine Devices Office of Product Evaluation and Quality Center for Devices and Radiological Health Enclosure {3}------------------------------------------------ # Indications for Use 510(k) Number (if known) K231337 Device Name EndeavorRx #### Indications for Use (Describe) EndeavorRx is a digital therapeutic indicated to improve attention as measured by computer-based testing in children ages 8-17 years old with primarily inattentive or combined-type ADHD, who have demonstrated attention issue. Patients who engage with EndeavorRx demonstrate improvements in a digitally assessed measure Tests of Variables of Attention (TOVA) of sustained and selective attention and may not display benefits in typical behavioral symptoms, such as hyperactivity. EndeavorRx should be considered for use as part of a therapeutic program that may include: cliniciandirected therapy, medication, and/ or educational programs, which further address symptoms of the disorder. Type of Use (Select one or both, as applicable) | | | |--------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------| |--------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------| X Prescription Use (Part 21 CFR 801 Subpart D) | | Over-The-Counter Use (21 CFR 801 Subpart C) #### CONTINUE ON A SEPARATE PAGE IF NEEDED. This section applies only to requirements of the Paperwork Reduction Act of 1995. #### *DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.* The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to: > Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff(@fda.hhs.gov "An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number." {4}------------------------------------------------ ## 8. 510(k) Summary This 510(k) summary of safety and effectiveness information is prepared in accordance with 21 CFR § 807.92. | Date Prepared: | May 5, 2023 | |-------------------------|---------------------------------------------------------------------------------------| | Legal Manufacturer: | Akili Interactive Labs, Inc.
125 Broad Street, 5th Floor
Boston, MA 02110 | | Primary Contact Person: | Bhupinder Singh
Head of Quality and Regulatory Affairs
Phone: +1 (408) 832-7124 | | | E-mail: bsingh@akiliinteractive.com | #### Regulatory Information | Device Trade Name: | EndeavorRx | |------------------------------|------------------------------------------------------------------------------| | Device Classification Name: | Digital Therapeutic Software for Attention Deficit
Hyperactivity Disorder | | Regulation Number: | 21 CFR § 882.5803 | | Classification Product Code: | QFT | | Review Advisory Committee: | Neurology | | Device Classification: | Class II | # Predicate Device Information | Device Manufacturer: | Akili Interactive Labs, Inc. | |----------------------|------------------------------| |----------------------|------------------------------| - Submission Number: DEN200026 - Device Name: EndeavorRx {5}------------------------------------------------ Image /page/5/Picture/0 description: The image shows the word ".KILI" in white font against a blue background. The font is stylized with rounded edges and a slightly futuristic look. The dot before "KILI" is small and round, and the letters themselves are bold and sans-serif. Device Description: EndeavorRx is a modification to the previously granted EndeavorRx (DEN200026) with the primary difference being the expansion of the indicated patient population from 8-12 years old to 8-17 years old. In addition, minor software changes were made to improve app accessibility and user engagement. The core therapeutic software technology was not changed. > EndeavorRx is a prescription-only digital therapeutic software indicated for use in the treatment of attention impairment in pediatric patients (8-17 years of age) with primarily inattentive or combinedtype ADHD. EndeavorRx is a software-as-a-medical device (SaMD) that resides on the user's mobile device and can be executed at home. > EndeavorRx is engineered as a therapeutically active treatment for attention in pediatric patients affected by ADHD. EndeavorRx is built on Akili's proprietary, patented, technology platform and uses adaptive algorithms (also known as Selective Stimulus Management Engine, SSME™) to deliver stimuli that are designed to engage the patient in a manner that improves their attention function. In a closedloop system, the adaptive SSME™ algorithms automatically adjust the difficulty level for a personalized treatment experience that is tailored to the needs of each individual patient. > EndeavorRx is delivered through a video game experience which leverages art, music, storytelling, and reward cycles to keep patients engaged. The adaptive algorithm constantly pushes patients precisely at predefined performance bounds relative to each individual, such that they are continuously encouraged to exceed their historic performance. The science behind EndeavorRx was developed at the University of California, San Francisco by Adam Gazzaley, M.D., Ph.D., Founding Director of the University of California San Francisco's Neuroscape and Akili's Chief Science Advisor. > The basic program inputs are steering, which is accomplished by using the mobile device's internal accelerometer to measure the degree to which it is tilted, and tapping, which is accomplished using the touch screen to measure correct and incorrect targeting. The basic outputs are the visual display of the game progression along with audio, which is accomplished by using the internal high resolution display and internal speaker. The program includes features to ensure it is used per the prescribed regimen (approximately 25 minutes per day, 5 days per week, for 4 weeks or as recommended by the health care provider). Indications for Use: EndeavorRx is a digital therapeutic indicated to improve attention #### AKILI CONFIDENTIAL Akili Interactive Labs, Inc. Premarket Notification [510(k) Submission] EndeavorRx {6}------------------------------------------------ Image /page/6/Picture/0 description: The image shows the word ".KILI" in white font against a blue background. The font is stylized with rounded edges and a modern look. The dot before "KILI" is small and round, and the letters are spaced closely together. | | function as measured by computer-based testing in children ages 8-17 years old with primarily inattentive or combined-type ADHD, who have demonstrated attention issue. Patients who engage with EndeavorRx demonstrate improvements in a digitally assessed measure Tests of Variables of Attention (TOVA) of sustained and selective attention and may not display benefits in typical behavioral symptoms, such as hyperactivity. EndeavorRx should be considered for use as part of a therapeutic program that may include: clinician-directed therapy, medication, and/or educational programs, which further address symptoms of the disorder. | |-------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------| | Limitations | Prescription-only medical device restricted to sale by or on the order of a licensed health care provider. | | | EndeavorRx may not be appropriate for patients with photo-sensitive epilepsy, color blindness, or physical limitations that restrict use of a mobile device; parents should consult with their child's health care provider. | | | This single arm study did not include a sham control group and it is therefore possible that a placebo effect may have impacted the study results by inflating the effect of the EndeavorRx device. The study had sufficient statistical power to detect a significant effect of treatment compared to a similarly sized control group with placebo response of up to a 1.7-point improvement in TOVA-ACS. Patients and health care providers should consider the totality of the clinical evidence in light of this before using this product. | | Attribute | Subject Device:
EndeavorRx v3.0 | Predicate Device:
EndeavorRx (DEN200026) | Comparison | |----------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------| | Manufacturer | Akili Interactive Labs, Inc. | Akili Interactive Labs, Inc. | Same | | Device
Classification Name | Digital Therapeutic Software
for Attention Deficit
Hyperactivity Disorder | Digital Therapeutic Software
for Attention Deficit
Hyperactivity Disorder | Same | | Product Code | QFT | QFT | Same | | Regulation Number | 21 CFR § 882.5803 | 21 CFR § 882.5803 | Same | | Intended Use | Digital therapeutic adaptive
stimulus software for the
closed-loop treatment of | Digital therapeutic adaptive
stimulus software for the
closed-loop treatment of | Same | | | psychiatric disorders and
cognitive dysfunction
associated with medical
conditions. | psychiatric disorders and
cognitive dysfunction
associated with medical
conditions. | | | Indications for Use | EndeavorRx is a digital
therapeutic indicated to
improve attention function as
measured by computer based
testing in children ages 8-17
years old with primarily
inattentive or combined-type
ADHD, who have a
demonstrated attention issue.
Patients who engage with
EndeavorRx demonstrate
improvements in a digitally
assessed measure Tests of
Variables of Attention (TOVA)
of sustained and selective
attention and may not display
benefits in typical behavioral
symptoms, such as
hyperactivity. EndeavorRx
should be considered for use
as part of a therapeutic
program that may include:
clinician-directed therapy,
medication, and/or
educational programs, which
further address
symptoms of the disorder. | EndeavorRx is a digital
therapeutic indicated to
improve attention function as
measured by computer based
testing in children ages 8-12
years old with primarily
inattentive or combined-type
ADHD, who have a
demonstrated attention issue.
Patients who engage with
EndeavorRx demonstrate
improvements in a digitally
assessed measure Tests of
Variables of Attention (TOVA)
of sustained and selective
attention and may not display
benefits in typical behavioral
symptoms, such as
hyperactivity. EndeavorRx
should be considered for use
as part of a therapeutic
program that may include:
clinician-directed therapy,
medication, and/or
educational programs, which
further address symptoms of
the disorder. | Substantially
equivalent.
EndeavorRx v3.0
is indicated for a
larger range of
pediatric
patients (8-17
years of age)
compared to the
predicate device
(8-12 years of
age). This does
not change the
intended use of
the device, and
clinical testing
demonstrates
the subject
device is safe and
effective in the
expanded
population. | | System
Components | Patient facing video game
application
Mobile device platform | Patient facing video game
application
Mobile device platform | Same | | Proprietary
Algorithm | Selective Stimulus
Management Engine
(SSMETM) | Selective Stimulus
Management Engine
(SSMETM) | Same | | Basic Operations | Steering, Tapping, Multi-
tasking | Steering, Tapping, Multi-
tasking | Same | | Presentation | Structured manner across | Structured manner across | Same | | | game "Challenges" and
"Worlds" | game "Challenges" and
"Worlds" | | | Mobile Platform
Compatibility | iOS and Android | iOS | Substantially
equivalent.
Addition of
Android
compatibility
does not present
different
questions. | | Access | Prescription use only.
Authorized and overseen by a
licensed health care provider. | Prescription use only.
Authorized and overseen by a
licensed health care provider. | Same | ## Summary Comparison of technological Characteristics {7}------------------------------------------------ # .KILI {8}------------------------------------------------ Image /page/8/Picture/0 description: The image shows the word ".AKILI" in white font against a blue background. The font is stylized with rounded edges and unique shapes for each letter. The dot before "AKILI" is a small circle, and the "A" is shaped like a triangle with a rounded top. Summary of Non-Clinical Performance Data: Bench software testing has been performed on the EndeavorRx and demonstrates compliance with the following international and FDA-recognized consensus standards and FDA guidance documents: - ISO 14971:2019 Medical devices - Application of risk management to medical devices - IEC 62304 Edition 1.1 2015-06 CONSOLIDATED VERSION ● Medical device software - Software life cycle processes - IEC 82304-1 Edition 1.0 2016-10 Health software - Part 1: General requirements for product safety - FDA Guidance Document for Industry and FDA Staff -Guidance for the content of Premarket Submissions for Software Contained in Medical Devices, issued May 11, 2005 - . FDA Guidance Document for Industry and FDA Staff -Content of Premarket Submissions for Management of Cybersecurity in Medical Devices, issued October 2, 2015 The results of bench software verification and validation testing supports that EndeavorRx functions as intended. Summary of Clinical performance testing was conducted to evaluate the efficacy and safety Clinical Data: of EndeavorRx in adolescents 13 to 17 years of age. Efficacy was determined primarily by the change from baseline in a digitally assessed measure of sustained and selective attention, the Test of Variables of Attention (TOVA®), after 4 weeks of treatment. The multi-center open-label study enrolled 162 adolescents subjects with inattentive or combined-type ADHD. The results of the clinical performance study support the performance and safety of #### AKILI CONFIDENTIAL Akili Interactive Labs, Inc. Premarket Notification [510(k) Submission] EndeavorRx {9}------------------------------------------------ Image /page/9/Picture/0 description: The image shows the word ".KILI" in white font against a blue background. The font is stylized with rounded edges and a modern look. The dot before "KILI" is small and round, and the letters are evenly spaced. EndeavorRx in the expanded pediatric age range. Analysis of the primary efficacy endpoint in the Efficacy Population (N=146) showed a significant positive mean change from baseline to study day 28 in the TOVA of 2.639 (SD 3.7986 [95% Cl: 2.018, 3.261]; P < 0.0001). Overall, 4 (2.5%) subjects experienced a treatmentemergent adverse device event (3 decreased frustration tolerance, 1 headache; all mild or moderate). There were no serious adverse device events. Prior clinical trial results that supported the original clearance of EndeavorRx for 8-12 year old patients under DEN200026 support the use of EndeavorRx in the younger cohort. The clinical performance studies demonstrate that EndeavorRx is safe and effective for its intended use in the indicated patient population. Table of Complete Case Analysis (CCA) and Intent-to-Treat (ITT) Analysis with Multiple Imputation (MI) of the Primary Efficacy Endpoint – TOVA-ACS Change from Baseline to Day 28 | Analysis | Baseline | Exit (Day 28) | Change from | |-----------------------------------|-----------------|-----------------|----------------| | | TOVA-ACS | TOVA-ACS | Baseline | | STARS ITT Population | | | | | n | 179 | 170 | 169 | | Mean (SE) | -5.11 (0.22) | -4.16 (0.28) | 0.93 (0.24) | | 95% CI | | | 0.45, 1.40 | | p-value1 | | | 0.0002 | | Efficacy Population (CCA, assumes | | | | | MCAR) | | | | | n | 146 | 146 | 146 | | Mean (SE) | -5.447 (0.3106) | -2.808 (0.3546) | 2.639 (0.3144) | | 95% CI | | | 2.018, 3.261 | | p-value1 | | | <0.0001 | | Safety Population (ITT with MI,2 | | | | | assumes MAR) | | | | | n | 162 | 162 | 162 | | Mean (SE) | -5.421 (0.2870) | -2.784 (0.3486) | 2.637 (0.3147) | | 95% CI | | | 2.020, 3.253 | | p-value1 | | | <0.0001 | Abbreviations: CCA = complete case analysis; ITT = intent-to-treat, MI = multiple imputation; MCAR = missing completely at random; MAR = missing at random; FCS = fully conditional specification {10}------------------------------------------------ Image /page/10/Picture/0 description: The image shows the word ".AKILI" in white font against a blue background. The font is stylized with rounded edges and a modern look. The dot before the word "AKILI" is small and round. 1 From a one-sample t-test of change greater than zero. Positive changes indicate improvement. 2 Multiple imputation for participants with missing data at Day 28 was performed using FCS with 100 imputations and included covariates age, sex, race, ethnicity, education plan, age of ADHD symptom onset, concomitant stimulant use, treatment exposure defined as number of non-practice missions completed, and baseline TOVA-ACS value. Estimates of mean and standard error at baseline, Day 28 and change from baseline were calculated for each imputation and combined using PROC MIANALYZE in SAS version 9.4. Clinical Study Comparison Summary Table | | Clinical Study for Subject
Device EndeavorRx v3.0
(K231337) | Clinical Study for
Predicate Device
(DEN200026) | Comparison | |---------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------| | | Adolescents
(ages 13-17) | STARS
(ages 8-12) | | | Population Under
Study | Verified ADHD diagnosis
with impaired attention;
on or off medication | Verified ADHD
diagnosis with
impaired attention;
medication
exclusionary | Similar - adolescent study
allowed for medication as
long as use was stable for ≥4
weeks prior to study
enrollment and throughout
the study. A prior study
demonstrated benefits of
intervention on the pediatric
population with ADHD both
on and off medication. | | Study Design | Single arm, open label;
25 min/day, 5
days/week, 4 weeks;
multi-site study across
US | Randomized,
controlled, parallel
arm; 25 min/day, 5
days/week, 4
weeks; multi-site
study across US | Different -the adolescent
study intended for
evaluation of substantial
equivalence via comparison
of results to the STARS AKL-
T01 group. The company
made a decision not to
include a control/sham arm
as part of this study for three
primary reasons:
1) the safety and efficacy of
the product was already | | | Clinical Study for Subject
Device EndeavorRx v3.0
(K231337) | Clinical Study for
Predicate Device
(DEN200026) | Comparison | | | Adolescents
(ages 13-17) | STARS
(ages 8-12) | | | | | | established in a randomized
controlled trial in the younger
population;2) the primary
endpoint used in STARS-
Adolescent was identical to
the original STARS RCT; and
3) based on the predicate
RCT and multiple published
studies of ADHD children and
adolescents in the literature,
the primary outcome
measure demonstrates little
to no placebo effects in
randomized, controlled
trials. | | Outcomes | Significant treatment
effect on primary
outcome measure
(attention function);
treatment effects in key
prespecified secondary
outcomes (ADHD
symptoms) | Significant
treatment effect on
primary outcome
measure (attention
function);
treatment effects in
key prespecified
secondary
outcomes
(responder analysis
for impairment) | Similar - primary outcomes
are the same. Both studies
had ADHD-RS as secondary
measures. Whereas the
STARS study listed multiple
secondary measures, the
adolescent study focused on
ADHD-RS as the secondary
measure, which previous
studies showed to be
sensitive to the AKL-T01
treatment. The TOVA-ACS
(primary outcome) is not
susceptible to placebo effect
when measuring attentional
control processes within the
context of ADHD, and this is
supported by the predicate
RCT and multiple published | | | Clinical Study for Subject
Device EndeavorRx v3.0
(K231337) | Clinical Study for
Predicate Device
(DEN200026) | Comparison | | | Adolescents
(ages 13-17) | STARS
(ages 8-12) | | | | | | studies in the literature. | | Safety | Low rates of adverse
device events; no
serious adverse device
events; no study
discontinuations related
to adverse device events | Low rates of
adverse device
events; no serious
adverse device
events; no study
discontinuations
related to adverse
device events | Similar | {11}------------------------------------------------ Image /page/11/Picture/0 description: The image shows the word ".KILI" in white font against a blue background. The font is stylized with rounded edges and a modern look. The dot before "KILI" is small and round, while the letters are bold and have a uniform thickness. {12}------------------------------------------------ Image /page/12/Picture/0 description: The image shows the word ".KILI" in white against a blue background. The letters are stylized with rounded edges and a modern font. The dot before the word is small and round, while the letters themselves are bold and easily readable. # Clinical Study Design Comparison Table | Study Design | Clinical Study for
Subject Device
EndeavorRx v3.0
(K231337)
Adolescents
(ages 13-17) | Clinical Study for
Predicate Device
(DEN200026)
STARS
(ages 8-12) | Comparison | |-----------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------| | Study design | Single-arm, open-label | Randomized clinical
trial | Different - the adolescent
study intended for
evaluation of substantial
equivalence via comparison of
results to the STARS AKL-T01
group. The company made a
decision not to include a
control/sham arm as part of
this study for three primary
reasons:
1) the safety and efficacy of
the product was already
established in a randomized | | Study Design | Clinical Study for
Subject Device
EndeavorRx v3.0
(K231337)
Adolescents
(ages 13-17) | Clinical Study for
Predicate Device
(DEN200026)
STARS
(ages 8-12) | Comparison | | | | | controlled trial in the younger
population;2) the primary
endpoint used in STARS-
Adolescent was identical to the
original STARS RCT.; and 3)
based on the predicate RCT
and multiple published studies
of ADHD children and
adolescents in the literature,
the primary outcome measure
demonstrates little to no
placebo effects in randomized,
controlled trials Additionally,
4) AKL-T01 is a low-risk device,
and 5) the predicate study
(STARS) was an RCT using the
same device that already
showed the effectiveness of
AKL-T01 against an active
control. Therefore, comparison
of the device's effectiveness to
active control was not part of
the study design rationale. | | Sites | Multi-site: 14 sites
across the US (a mix of
institutional sites and
private practice
centers) | Multi-site: 20 sites
across the US (a mix
of institutional sites
and private practice
centers) | Similar… --- **Source:** [https://fda.innolitics.com/submissions/NE/subpart-f%E2%80%94neurological-therapeutic-devices/QFT/K231337](https://fda.innolitics.com/submissions/NE/subpart-f%E2%80%94neurological-therapeutic-devices/QFT/K231337) **Published by [Innolitics](https://innolitics.com)** — a medical-device software consultancy. We help companies design, build, and clear FDA-regulated software and AI/ML devices. If you're preparing [a 510(k)](https://innolitics.com/services/510ks/), [a De Novo](https://innolitics.com/services/regulatory/), [a SaMD](https://innolitics.com/services/end-to-end-samd/), [an AI/ML medical device](https://innolitics.com/services/medical-imaging-ai-development/), or [an FDA regulatory strategy](https://innolitics.com/services/regulatory/), [get in touch](https://innolitics.com/contact). **Cite:** Innolitics at https://innolitics.com