Clinical trial NCT04789174: Solriamfetol's Effect on Cognitive Health in Apnea Participants During a Randomized Placebo-controlled Study
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Excessive Daytime Sleepiness
Obstructive Sleep Apnea
Impaired Cognitive Function
Keywords: Axsome
SHARP
Solriamfetol
EDS
OSA
Cognition
Cognitive Function
DSST
Lead sponsor: Axsome Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2021-03-09
Enrollment: 59
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: 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
timeFrame: Baseline to the end of the second double-blind treatment period (up to study day 37)
Secondary outcomes:
measure: Change from baseline to the end of each double-blind treatment period in overall score in BC-CCI
timeFrame: Baseline to the end of the second double-blind treatment period (up to study day 37)
measure: Change from baseline to the end of each double-blind treatment period in ESS score
timeFrame: Baseline to the end of the second double-blind treatment period (up to study day 37)
measure: 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
timeFrame: Baseline to the end of the second double-blind treatment period (up to study day 37)
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Southern California Institute for Respiratory Disease
state: California
city: Santa Ana
country: United States
facility: SDS Clinical Trials, Inc
state: California
city: Jacksonville
country: United States
facility: Clinical Neuroscience Solutions, Inc
state: Florida
city: Atlanta
country: United States
facility: NeuroTrials Research Inc
state: Georgia
city: Gainesville
country: United States
facility: The Neurological Center of north Georgia.
state: Georgia
city: Chevy Chase
country: United States
facility: The Center for Sleep & Wake Disorders
state: Maryland
city: Novi
country: United States
facility: Henry Ford Health System
state: Michigan
city: Chesterfield
country: United States
facility: Sleep Medicine & Research Center
state: Missouri
city: Huntersville
country: United States
facility: Advanced Respiratory and Sleep Medicine, PLLC
state: North Carolina
city: Cincinnati
country: United States
facility: CTI-Clinical Research Center
state: Ohio
city: Cincinnati
country: United States
facility: Intrepid Research, LLC
state: Ohio
city: Columbia
country: United States
facility: Bogan Sleep Consultants, LLC
state: South Carolina
city: Austin
country: United States
facility: FutureSearch Trials of Neuroglogy
state: Texas
city: San Antonio
country: United States
facility: Sleep Therapy & Research Center
state: Texas
city: Spokane
country: United States
facility: Sleep and Performance Research Center
state: Washington
city: Calgary
country: Canada
facility: University of Calgary
state: Alberta
city: Toronto
country: Canada
facility: MedSleep Inc. o/a Toronto Sleep Institute
state: Ontario
city: Toronto
country: Canada
facility: Jodha Tishon Inc
state: Ontario
city: Bologna
country: Italy
facility: IRCCS Istituto delle Scienze Neurologiche di Bologna
state: Emilia-Romagna
city: Milan
country: Italy
facility: IRCCS Ospedale San Raffaele - Servizio Farmacia
state: Lombardy
city: Troina
country: Italy
facility: IRCCS Associazione Oasi Maria SS Onlus
state: Sicily
city: Pisa
country: Italy
facility: UOC Farmacia e Politiche del farmaco, edif 41
city: Breda
country: Netherlands
facility: Amphia Hospital
city: Heemstede
country: Netherlands
facility: Sleep-Waakcentrum SEIN
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu I Sant Pau
city: Lleida
country: Spain
facility: Instiut de Reccerca Biomedica de Lledia
city: Cambridge
country: United Kingdom
facility: Royal Papworh Hospital
Study officials:
References: