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

Phase 1

• Conditions: Impaired cognitive function in patients with excessive daytime sleepiness associated with obstructive sleep apnea; MedDRA version: 21.1Level: LLTClassification code 10055577Term: Obstructive sleep apnea syndromeSystem Organ Class: 100000004855; Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

• Registration Number: EUCTR2020-004243-92-NL
• Lead Sponsor: Jazz Pharmaceuticals, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-04-13
• Last Update Posted: 12 July 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 164

Inclusion Criteria

Age and Sex
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.
Type of Participant and Disease Characteristics
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. The participant has an age-corrected scaled score = 8 on the DSST Wechsler Adult Intelligence Scale, Fourth Edition (WAIS-IV) at the Screening visit.
5. British Columbia-Cognitive Complaints Inventory = 9 at Screening and Baseline.
6. Epworth Sleepiness Scale (ESS) score > 10 at Screening and Baseline.
7. Usual nightly total sleep time of = 6 hours.
Weight
8. Body mass index from 18.5 to < 40 kg/m2.
Sex and Contraceptive/Barrier Requirements
9. Male and female Participants
a. Male participants:
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 as detailed below
• Agree to use a male condom with female partner use of an additional highly effective contraceptive method with a failure rate of < 1% per year as described in Appendix 5 Contraceptive and Barrier Requirements when having sexual intercourse with a women of childbearing potential (WOCBP) who is not currently pregnant.
b. Female participants:
• 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) as defined in Appendix 5 Contraceptive and Barrier Guidance
OR
- Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of < 1% per year), as described in 0 Contraceptive and Barrier Guidance during the study intervention period and for at least 14 days after the last dose of study intervention. The investigator should evaluate the potential for contraceptive method failure (eg, noncompliance, recently initiated) in relationship to the first dose of study intervention.
• A WOCBP must have a negative highly sensitive pregnancy test (urine or serum as required by local regulations) within the Screening/Baseline period (once at the time of Screening for participation in the study and again at the time of the study Baseline assessment) before the first dose of study intervention, see Section 8.4.5 Pregnancy Testing.
• Additional requirements for pregnancy testing during and after study intervention are located in

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; including history or presence of neurodegenerative condition (eg, mild cognitive impairment due to Alzheimer’s), autism, vascular dementia, active suicidal ideation, that could affect the safety of the participant or interfere with study efficacy, safety, conduct or the ability of the participant to complete the trial based on the judgment of the investigator.
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 including but not limited to: myocardial infarction within the past year, unstable angina pectoris, symptomatic congestive heart failure (ACC/American Heart Association stage C or D), revascularization procedures within the past year, uncontrolled atrial fibrillation, ventricular cardiac arrhythmias requiring automatic implantable cardioverter defibrillator or medication therapy, uncontrolled hypertension (as defined by Centers for Disease Control and Prevention), systolic blood pressure = 155 mmHg or diastolic blood pressure = 95 mmHg (at Screening or Baseline), or any history of cardiovascular disease or any significant cardiovascular condition that in the investigator’s opinion may jeopardize participant safety in the study.
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 B

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified