Twelve-week Study of the Safety and Efficacy of JZP-110 in the Treatment of Excessive Sleepiness in Narcolepsy

Study Overview
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Brief Summary
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This trial is a 12-week, randomized, double-blind, placebo controlled, multicenter, 4-treatment parallel group study of the safety and efficacy of JZP-110 in the treatment of excessive sleepiness in adult subjects with narcolepsy.

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 Narcolepsy

Conditions
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Narcolepsy

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: Males and females between 18 and 75 years of age, inclusive Diagnosis of narcolepsy according to ICSD-3 or DSM-5 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 Moderate or severe sleep apnea on the baseline PSG. Any other clinically relevant medical, behavioral, or psychiatric disorder other than narcolepsy 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 gastic 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 Use of any medications that could affect the evaluation of cataplexy Received an investigational drug in the past 30 days or five half-lives (whichever is longer) Previous exposure to or participation in a previous clinical trial of JZP-110 (ADX-N05, R228060, 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 mg of JZP-110<br>Once Daily Dosing | Drug: JZP-110<br> <br> |
| Active Comparator: 150 mg 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> |
| Placebo 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. MWT sleep latency ranges from 0 to 40 minutes, with higher scores indicating greater ability to stay awake; a positive change from baseline represents improvement in the sleep latency time. Mean sleep latency defined as the average of the first 4 MWT trials, if 3 or 4 of them are non-missing. | 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 treatment starts on a 7-point scale ranging from 1= very much improved to 7= very much worse | Baseline to Week 12 | 
| Change in Sleep Latency Time on MWT Trial 1 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. | Change from baseline for sleep latency in MWT during trial 1 at week 12 | 
| Change in Sleep Latency Time on MWT Trial 2 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. | Change from baseline for sleep latency in MWT during trial 2 at week 12 | 
| Change in Sleep Latency Time on MWT Trial 3 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. | Change from baseline for sleep latency in MWT during trial 3 at week 12 | 
| Change in Sleep Latency Time on MWT Trial 4 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. | Change from baseline for sleep latency in MWT during trial 4 at week 12 | 
| Change in Sleep Latency Time on MWT Trial 5 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. | Change from baseline for sleep latency in MWT during trial 5 at 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 |