Six-week Study of the Safety and Efficacy of JZP-110 in the Treatment of Excessive Sleepiness in OSA

Study Overview
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Brief Summary
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This trial is a 6-week, double-blind, placebo-controlled, randomized-withdrawal, multicenter study of safety and efficacy of JZP-110 in the treatment of excessive sleepiness in adult subjects with OSA.

Official Title
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A Six-Week, Double-Blind, Placebo-Controlled, Randomized- Withdrawal, Multicenter Study of the Safety and Efficacy of JZP-110 [(R)-2-amino-3-phenylpropylcarbamate Hydrochloride] in the Treatment of Excessive Sleepiness in Subjects With Obstructive Sleep Apnea (OSA)

Conditions
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Obstructive Sleep Apnea

Intervention / Treatment
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* Drug: JZP-110


Participation Criteria
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Eligibility Criteria
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Major Inclusion Criteria: Male or female between 18 and 75 years of age, inclusive Diagnosis of OSA according to ICSD-3 criteria Body mass index from 18 to <45 kg/m2 Consent to use a medically acceptable method of contraception Willing and able to provide written informed consent Major Exclusion Criteria: Female subjects who are pregnant, nursing, or lactating. Any other clinically relevant medical, behavioral, or psychiatric disorder other than OSA that is associated with excessive sleepiness History or presence of bipolar disorder, bipolar related disorders, schizophrenia, schizophrenia spectrum disorders, or other psychotic disorders according to DSM-5 criteria History or presence of any acutely unstable medical condition, behavioral or psychiatric disorder (including active suicidal ideation), or surgical history that could affect the safety of the subject or interfere with study efficacy or safety assessments or the ability of the subject to complete the trial per the judgment of the principal investigator History of bariatric surgery within the past year or a history of any gastric bypass procedure Presence or history of significant cardiovascular disease Use of any over the counter (OTC) or prescription medications that could affect the evaluation of excessive sleepiness Received an investigational drug in the past 30 days or five half-lives (whichever is longer) Previous exposure to or participation in a clinical trial of JZP-110 (ADX-N05, R228060, or YKP10A) History of phenylketonuria (PKU) or history of hypersensitivity to phenylalanine-derived products

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 75, 150, 300 mg of JZP-110<br>Once Daily Dosing | Drug: JZP-110<br> <br> |
| Active Comparator: Placebo<br>Once Daily Dosing | Drug: JZP-110<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the Maintenance of Wakefulness Test (MWT) | Change in the mean sleep latency time as determined from the first four trials of a 40-minute MWT from the end of the Stable Dose Phase to the end of the Double-blind Withdrawal Phase. Mean sleep latency defined as the average of the first four MWT trial's measurements. | Week 4 to Week 6 | 
| Change in the Epworth Sleepiness Scale (ESS) | Change in Epworth Sleepiness Scale (ESS) score from the end of the Stable Dose Phase to the end of the Double-blind Withdrawal Phase. A negative change from baseline represents improvement in excessive sleepiness. The ESS is a self-administered questionnaire with 8 questions. Each activity is scored on a scale ranging from 0-3, with 0 = would never fall asleep, and 3 = high chance of falling asleep. The total score ranges from 0-24, with a higher number representing an increased propensity for sleepiness. An analysis of covariance (ANCOVA) was used for the analysis of ESS scores. The response variable was the change in ESS score from week 4 to week 6. | Week 4 to Week 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient Global Impression of Change (PGIc) | Percentage of subjects reported as worse (minimally, much, or very much) on the PGIc at the end of the Double-blind Withdrawal Phase. PGIc was rated by subjects and measures the change in their condition since treatment starts on a 7-point scale ranging from 1= very much improved to 7= very much worse. | Week 4 to Week 6 | 
| Clinical Global Impression of Change (CGIc) | Percentage of subjects reported as worse (minimally, much, or very much) on the CGIc at the end of the Double-blind Withdrawal Phase. CGIc was rated by clinicians and measures the change in the subject's condition since treatment starts on a 7-point scale ranging from 1= very much improved to 7= very much worse. | Week 4 to Week 6 | 
| Change in Functional Outcomes of Sleep Questionnaire (FOSQ-10) | Change is total score from the end of the stable dose phase to the end of the double blind withdrawal phase. Functional Outcomes of Sleep Questionnaire Short Version (FOSQ-10) is a 10-item disease-specific quality of life questionnaire to assess the effect of excessiveness sleepiness on multiple activities of everyday living. The FOSQ-10 consists of 10 questions, each scored on a scale from 1-4. The questionnaire has a 4-point response format for each question (1 = extreme difficulty, 2 = moderate difficulty, 3 = a little difficulty, and 4 = no difficulty). The total score is derived by the mean of the 5 subscale scores, multiplied by 5, resulting in a possible range of scores between 5 to 20; lower FOSQ-10 scores are worse, indicating more difficulty carrying out activities; higher FOSQ-10 scores are better, indicating less difficulty carrying out activities. | Week 4 to Week 6 |