Solriamfetol's Effect on Cognitive Health in Apnea Participants During a Randomized Placebo-controlled Study (SHARP)

Solriamfetol's Effect on Cognitive Health in Apnea Participants During a Randomized Placebo-controlled Study (SHARP): a 5-Week Double-blind, Placebo-controlled, Randomized, Crossover, Multicenter Study of Solriamfetol in Improving Cognitive Function in Participants With Excessive Daytime Sleepiness Associated With Obstructive Sleep Apnea Plus Impaired Cognitive Function

The purpose of study JZP110-405 is to determine whether solriamfetol is effective at improving cognitive function in participants with excessive daytime sleepiness (EDS) associated with obstructive sleep apnea (OSA) plus impaired cognitive function.

Study Overview

• Status: Completed
• Conditions: Obstructive Sleep Apnea; Excessive Daytime Sleepiness; Impaired Cognitive Function
• Intervention / Treatment: Drug: Placebo; Drug: Solriamfetol

• Study Type: Interventional
• Enrollment (Actual): 59
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N1
      • University of Calgary
  • Ontario
    • Toronto, Ontario, Canada, M4P 1P2
      • MedSleep Inc. o/a Toronto Sleep Institute
    • Toronto, Ontario, Canada, M5S 3A3
      • Jodha Tishon Inc
• Italy
  • Pisa, Italy, 56126
    • UOC Farmacia e Politiche del farmaco, edif 41
  • Emilia-Romagna
    • Bologna, Emilia-Romagna, Italy, 40139
      • IRCCS Istituto delle Scienze Neurologiche di Bologna
  • Lombardy
    • Milan, Lombardy, Italy, 20132
      • IRCCS Ospedale San Raffaele - Servizio Farmacia
  • Sicily
    • Troina, Sicily, Italy, 94018
      • IRCCS Associazione Oasi Maria SS Onlus
• Netherlands
  • Breda, Netherlands, 4818 CK
    • Amphia Hospital
  • Heemstede, Netherlands, 2104 SW
    • Sleep-Waakcentrum SEIN
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clinic de Barcelona
  • Barcelona, Spain, 08041
    • Hospital de la Santa Creu i Sant Pau
  • Lleida, Spain, 25198
    • Instiut de Reccerca Biomedica de Lledia
• United Kingdom
  • Cambridge, United Kingdom, CB23 3RE
    • Royal Papworh Hospital
• United States
  • California
    • Los Angeles, California, United States, 90048
      • Southern California Institute for Respiratory Disease
    • Santa Ana, California, United States, 92705
      • SDS Clinical Trials, Inc
  • Florida
    • Jacksonville, Florida, United States, 32256
      • Clinical Neuroscience Solutions, Inc
  • Georgia
    • Atlanta, Georgia, United States, 30328
      • NeuroTrials Research Inc
    • Gainesville, Georgia, United States, 30501
      • The Neurological Center of north Georgia.
  • Maryland
    • Chevy Chase, Maryland, United States, 20815
      • The Center for Sleep & Wake Disorders
  • Michigan
    • Novi, Michigan, United States, 48377
      • Henry Ford Health System
  • Missouri
    • Chesterfield, Missouri, United States, 63017
      • Sleep Medicine & Research Center
  • North Carolina
    • Huntersville, North Carolina, United States, 28078
      • Advanced Respiratory and Sleep Medicine, PLLC
  • Ohio
    • Cincinnati, Ohio, United States, 45245
      • Intrepid Research, LLC
    • Cincinnati, Ohio, United States, 45212
      • CTI-Clinical Research Center
  • South Carolina
    • Columbia, South Carolina, United States, 29201
      • Bogan Sleep Consultants, LLC
  • Texas
    • Austin, Texas, United States, 78731
      • FutureSearch Trials of Neuroglogy
    • San Antonio, Texas, United States, 78229
      • Sleep Therapy & Research Center
  • Washington
    • Spokane, Washington, United States, 99202
      • Sleep and Performance Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female between 18 (or the legal age of consent in the jurisdiction in which the study takes place) and 65 years of age, inclusive.
2. Diagnosis of OSA according to International Classification of Sleep Disorders, Third Edition criteria.

3. Participant report (with clinician concurrence) of at least 1 of the following primary OSA therapy criteria:

   • Consistent number of hours of primary PAP therapy use (with downloadable history) for OSA on at least 5 nights/week for at least 1 month prior to Baseline (with or without prior OSA surgical intervention), OR
   • No current use of PAP therapy for at least 1 month prior to Baseline but a history of at least 1 month of attempting to use PAP as the primary OSA therapy with at least 1 documented adjustment that was made in an attempt to optimize the therapy (with or without prior OSA surgical intervention), OR
   • History of a surgical intervention intended to treat OSA symptoms (with or without current PAP use as primary OSA therapy).
4. Usual nightly total sleep time of ≥ 6 hours.
5. Body mass index from 18.5 to < 40 kg/m2.

6. Male participants are eligible to participate if they agree to the following during the study intervention period and for at least 14 days after the last dose of study intervention:

   • Refrain from donating sperm

   PLUS, either:

   • Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agree to remain abstinent OR
   • Must agree to use contraception/barrier

7. A female participant is eligible to participate if she is not pregnant or breastfeeding, and 1 of the following conditions applies:

   • Is a woman of nonchildbearing potential (WONCBP) OR
   • Is a WOCBP and using a contraceptive method that is highly effective
8. Capable of giving signed informed consent.

Exclusion Criteria:

1. Female participants who are pregnant, nursing, or lactating.
2. Usual bedtime later than 1 AM (0100 hours).
3. Occupation requiring nighttime or variable shift work.
4. Unable to understand or perform DSST test per investigator's judgement.
5. Use a PAP machine with no adherence data downloadable ability.
6. Diagnosis of another sleep disorder (other than OSA) including: circadian rhythm sleep disorders, narcolepsy, restless legs syndrome determined by participant sleep history.
7. Presence of acutely unstable major depression or current major depressive episode as based on the judgement of the investigator.
8. Participants with active clinically significant illness, including endocrine, neoplastic, gastrointestinal, hematological, hepatic, immunologic, metabolic, neurological, pulmonary, and/or renal disease, and/or surgical history which could interfere with the study efficacy, safety, conduct or the ability of the participant to complete the study based on the judgement of the investigator, or place the participant at risk during the trial or compromise the study objectives.
9. History or presence of any other clinically relevant medical, behavioral, or psychiatric disorder other than OSA that is associated with an impact on cognitive function.
10. History or presence of bipolar disorder, bipolar related disorders, schizophrenia, schizophrenia spectrum disorders, or other psychotic disorders according to Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria.
11. History of bariatric surgery within the past year or a history of any gastric bypass procedure.
12. Participants with movement or motor disorders such as Parkinson's disease, as they will not be able to complete the DSST.
13. Presence of renal impairment or calculated creatinine clearance < 60 mL/minute.
14. Clinically significant ECG abnormality in the opinion of the investigator.
15. Presence of significant cardiovascular disease.
16. Laboratory value(s) outside the laboratory reference range that is considered to be clinically significant by the investigator (clinical chemistry, hematology, and urinalysis). NOTE: Screening labs may be repeated once.
17. Hypothyroidism or hyperthyroidism, unless stabilized by appropriate medication for at least 3 months prior to Screening (a normal thyroid-stimulating hormone is required prior to Randomization at Baseline).
18. Use of any over-the-counter (OTC) or prescription medications that could affect the evaluation of EDS within a time period prior to the Baseline visit corresponding to at least 5 half-lives of the drug(s) or planned use of such drug(s) at some point throughout the duration of the 5-week double-blind treatment period.
19. Current or recent (within the past 2 years) diagnosis of a moderate or severe substance use disorder (excluding caffeine) according to DSM-5 criteria, or seeking treatment for a substance-related disorder. Nicotine use disorder is excluded only if it has an effect on sleep (ie, a participant who routinely awakens at night to smoke).
20. Excessive caffeine use.
21. Urine drug screen positive for amphetamine, methamphetamine, tricyclic antidepressants, propoxyphene, benzodiazepines, barbiturates, cocaine, marijuana, morphine, ecstasy, oxycodone, buprenorphine, methadone, or phencyclidine at Screening or at any point throughout the duration of the study.
22. History of regular heavy use of tetrahydrocannabinol (THC) is excluded. Sporadic recreational users of THC can complete a repeat urine drug screen during the Screening period. If this is negative, the participant may be allowed to enter the study pending agreement to completely refrain from the use of THC during the course of the study.
23. Positive alcohol test at Screening.
24. Participants who binge drink, defined as 5 or more drinks in a day for men or 4 or more drinks in a day for women at least once in past month.
25. History of phenylketonuria or history of hypersensitivity to phenylalanine-derived products.
26. Currently receiving MAO inhibitors or having had received MAO inhibitors for 14 days prior to the Baseline visit.
27. Previous exposure to solriamfetol.
28. Received an investigational drug in the past 30 days or 5 half-lives (whichever is longer) prior to the Baseline visit, or plans to use an investigational drug (other than the study drug) during the study.
29. Is currently participating in another clinical study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Placebo
Active Comparator: Solriamfetol; Solriamfetol 75 mg/d Solriamfetol 150 mg/d	Drug: Solriamfetol; Solriamfetol 75 mg/d Solriamfetol 150 mg/d

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change from the average of the DSST RBANS scores at Baseline to the average of the postdose DSST RBANS scores at the end of each double-blind treatment period	Baseline to the end of the second double-blind treatment period (up to study day 37)

Secondary Outcome Measures

Outcome Measure	Time Frame
Change from baseline to the end of each double-blind treatment period in overall score in BC-CCI	Baseline to the end of the second double-blind treatment period (up to study day 37)
Change from baseline to the end of each double-blind treatment period in ESS score	Baseline to the end of the second double-blind treatment period (up to study day 37)
Change from each of the 2-, 4-, 6-, and 8-hour DSST RBANS sores at Baseline to each of the corresponding 2-, 4-, 6-, and 8-hour postdose DSST RBANS scores at the end of each double-blind treatment period	Baseline to the end of the second double-blind treatment period (up to study day 37)

Collaborators and Investigators

• Sponsor: Axsome Therapeutics, Inc.

Publications and helpful links

Helpful Links

• Axsome Therapeutics Website

Study record dates

Study Major Dates

• Study Start (Actual): May 17, 2021
• Primary Completion (Actual): September 19, 2022
• Study Completion (Actual): September 19, 2022

Study Registration Dates

• First Submitted: February 25, 2021
• First Submitted That Met QC Criteria: March 4, 2021
• First Posted (Actual): March 9, 2021

Study Record Updates

• Last Update Posted (Actual): October 17, 2022
• Last Update Submitted That Met QC Criteria: October 14, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: OSA; Cognition; Cognitive Function; Axsome; EDS; Solriamfetol; SHARP; DSST
• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Respiratory Tract Diseases; Respiration Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Signs and Symptoms, Respiratory; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Apnea; Disorders of Excessive Somnolence; Sleepiness
• Other Study ID Numbers: JZP110-405

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No