Excessive Daytime Sleepiness, Impaired Cognitive Function, Obstructive Sleep Apnea
Conditions
Keywords
Axsome, SHARP, Solriamfetol, EDS, OSA, Cognition, Cognitive Function, DSST
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.
Interventions
DRUGSolriamfetol
Solriamfetol 75 mg/d Solriamfetol 150 mg/d
DRUGPlacebo
Placebo
Sponsors
Axsome Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Average of the 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 5 weeks) | The DSST RBANS (Digit Symbol Substitution Test Repeatable Battery for the Assessment of Neuropsychological Status) is an objective neuropsychological test that assesses executive function, processing speed and attention. DSST RBANS scores range from a minimum of 0 (worse outcome) to a maximum of 100 (better outcome). The change from baseline was calculated as post-baseline - baseline. A positive change indicates improvement. |
Countries
Canada, Italy, Netherlands, Spain, United Kingdom, United States
Participant flow
Recruitment details
Crossover Design: Subjects meeting the entry criteria were randomized in a 1:1 ratio either to Sequence 1 (up to 150 mg solriamfetol daily for two weeks followed by placebo for two weeks) or Sequence 2 (placebo for two weeks followed by up to 150 mg solriamfetol daily for two weeks). Crossover treatment periods were separated by a 1-week washout period.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 52.5 years STANDARD_DEVIATION 10.48 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 43 Participants |
| Sex: Female, Male Female | 10 Participants |
| Sex: Female, Male Male | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 59 | 0 / 59 |
| other Total, other adverse events | 6 / 59 | 1 / 59 |
| serious Total, serious adverse events | 0 / 59 | 0 / 59 |
Outcome results
None listed