Twelve-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 12 week, randomized, double-blind, placebo controlled, multicenter, 5-arm parallel group 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 Twelve-Week, Double-Blind, Placebo-Controlled, Randomized, Parallel-Group, 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
* Drug: Placebo oral tablet


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, safety, PK assessments, or the ability of the subject to complete the trial per the judgment of the 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 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: 37.5 mg of JZP-110<br>Once Daily Dosing | Drug: JZP-110<br> <br> |
| Active Comparator: 75 mg of JZP-110<br>Once Daily Dosing | Drug: JZP-110<br> <br> |
| Active Comparator: 150 mg of JZP-110<br>Once Daily Dosing | Drug: JZP-110<br> <br> |
| Active Comparator: 300 mg of JZP-110<br>Once Daily Dosing | Drug: JZP-110<br> <br> |
| Active Comparator: Placebo<br>Once Daily Dosing | Drug: Placebo oral tablet<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Maintenance of Wakefulness Test (MWT) From Baseline to Week 12 | Change in mean sleep latency time (in minutes) as determined from the first 4 trials of a 40-minute MWT from baseline to Week 12. | Baseline to Week 12 | 
| Change in ESS Score From Baseline to Week 12 | Change in Epworth Sleepiness Scale (ESS) score from Baseline to Week 12. 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 baseline. | Baseline to Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subjects Reported Improved on the Patient Global Impression of Change (PGIc) at Week 12 | Percentage of subjects reported as improved (minimally, much, or very much) on the PGIc at Week 12. PGIc was rated by subjects and measures the change in their condition since start of treatment on a 7-point scale ranging from 1 = very much improved to 7 = very much worse. This is the key secondary endpoint. | 12 Weeks | 
| Change in Sleep Latency Time on Each of the 5 MWT Trials at Week 12 | Time course of efficacy in MWT: Change in sleep latency (in minutes) on each of the 5 MWT trials at week 12. | Baseline and Week 12 | 
| Change in the Mean Sleep Latency Time as Determined From the First 4 Trials of a 40-minute MWT From Baseline to Week 4 | Change in mean sleep latency time (in minutes) as determined from the first 4 trials of a 40-minute MWT from baseline to week 4. | Baseline to Week 4 | 
| Change in ESS Score From Baseline to Week 1, Week 4, and Week 8 | Change in Epworth Sleepiness Scale (ESS) score from Baseline to Weeks 1, 4, and 8. 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 baseline. | Baseline to Weeks 1, 4, and 8 | 
| Percentage of Subjects Reported as Improved on the PGIc at Week 1, Week 4, and Week 8 | Percentage of subjects reported as improved (minimally, much, or very much) on the PGIc at Week 1, Week 4, and Week 8. PGIc was rated by subjects and measures the change in their condition since treatment start on a 7-point scale ranging from 1 = very much improved to 7 = very much worse. | Weeks 1, 4, and 8 | 
| Percentage of Subjects Reported as Improved on the Clinical Global Impression of Change (CGIc) at Week 12 | Percentage of subjects reported as improved (minimally, much, or very much) on the CGIc at Week 12. 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 12 | 
| Percentage of Subjects Reported as Improved on the CGIc at Week 1, Week 4, and Week 8 | Percentage of subjects reported as improved (minimally, much, or very much) on the CGIc at Week 1, Week 4, and Week 8. 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. | Weeks 1, 4, and 8 |