A Study of the Efficacy and Safety of JZP-258 in Subjects With Narcolepsy With Cataplexy

Jazz Pharmaceuticals201 enrolled

Overview

This is a double-blind, placebo-controlled, randomized-withdrawal, multicenter study of the efficacy and safety of JZP-258.

Subjects will be transitioned to JZP-258 based on their treatment status at study entry. All subjects will begin JZP-258 treatment at the beginning of this period and continue through Week 12. They will be treated with JZP-258 alone for the final two weeks of this 12-week period. Once the JZP-258 dose has been optimized per the Investigator's judgment, these subjects may enter the 2-week Stable-Dose Period with that dose. Subjects are eligible to enter the Double-Blind Randomized-Withdrawal Period if the dose of JZP-258 remains unchanged during the Stable-Dose Period and, in the judgment of the Investigator, no clinically significant worsening in narcolepsy symptoms or clinically significant adverse events due to JZP-258 treatment have occurred. Subjects will return for a Safety Follow-up visit 2 weeks after the Double-Blind Randomized-Withdrawal Period. Subjects who complete the double-blind treatment period during the Main Study are eligible to enter a 24-week Open-Label Extension. During this period subjects will receive open label JZP-258. Subjects will return for a Safety Follow-up visit 2 weeks after the Open-Label Extension Period.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

201

Conditions

Narcolepsy With Cataplexy

Interventions

JZP-258DRUG

JZP-258 oral solution 0.5 g/mL, which is equivalent to 0.413 g/mL of oxybate

PlaceboOTHER

Matching placebo solution (aqueous solution containing sodium citrate, malic acid, and sucralose; all ingredients were compendial \[United States Pharmacopeia/ National Formulary\])

Eligibility

Sex: ALLMin age: 18 YearsMax age: 70 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Male or female subjects between 18 and 70 years of age, inclusive. 2. Have a primary diagnosis of narcolepsy with cataplexy that meets ICSD-3 criteria or DSM-5 criteria, and currently untreated or treated with or without anticataplectics. 3. If applicable, treated with a stimulant or alerting agent at unchanged doses for at least 2 months prior to dosing or not treated with a stimulant or alerting agent. 4. Willing and able to comply with the study design schedule and other requirements. 5. Willing and able to provide written informed consent. Exclusion Criteria: 1. Narcolepsy secondary to another medical condition (e.g., CNS injury or lesion) 2. History or presence of any unstable or clinically significant medical condition, behavioral or psychiatric disorder (including active suicidal ideation), or history or presence of another neurological disorder or surgical history that might affect the subject's safety and/or interfere with the conduct of the study in the opinion of the Investigator. 3. Treatment with any central nervous system sedating agents, including but not limited to benzodiazepines, nonbenzodiazepine anxiolytics/ hypnotics/sedatives, neuroleptics, opioids, barbiturates, phenytoin, ethosuximide, or MCT inhibitors, e.g. diclofenac, valproate, ibuprofen, within 2 weeks prior to enrollment (discontinuation for the purpose of study enrollment is permitted only if considered safe by the Investigator and approved by the Medical Monitor). 4. Treatment with an antidepressant for cataplexy, if the withdrawal of the antidepressant during cross-titration with JZP-258 might be unsafe due to prior history of depression. 5. Unsafe for the subject to receive placebo treatment for 2 weeks, in the opinion of the Investigator.

Locations (25)

SDS Clinical Trials, Inc.

Orange, California, United States

Outcomes

Primary Outcomes

Change in Weekly Number of Cataplexy Attacks

Participants completed a daily Cataplexy Frequency Diary each night prior to bedtime. Participants were to record the number of cataplexy attacks that they had each day.

Time frame: Change from baseline (2 weeks of the Stable Dose Period) to the 2 weeks of the Double Blind Randomized Withdrawal Period (DB RWP)

Secondary Outcomes

Change in the Epworth Sleepiness Scale (ESS) Score

This is the key secondary endpoint. The Epworth Sleepiness Scale (ESS) was a self-administered questionnaire with 8 questions. Participants were asked to rate, on a 4-point scale (0-3), their usual chances of dozing off or falling asleep while engaged in eight different activities. Most participants engaged in those activities at least occasionally, although not necessarily every day. The ESS score (the sum of 8 item scores, 0-3) can range from 0 to 24. The higher the ESS score, the higher that participants average sleep propensity in daily life (ASP), or their 'daytime sleepiness'.

Time frame: From the end of the Stable Dose Period to the end of the Double Blind Randomized Withdrawal Period

Number of Participants With Worsening Patient Global Impression of Change (PGIc) for Narcolepsy Overall

At the end of the Double Blind Randomized Withdrawal Period (DB RWP), participants rated the change in their condition on a 7-point scale ranging from 1 = "very much improved" to 7 = "very much worse" since the last visit. This endpoint measures the percentage of participants with worsening PGIc scores for narcolepsy overall (defined as scores of Much Worse or Very Much Worse).

Time frame: At the end of the Double Blind Randomized Withdrawal Period

Number of Participants With Worsening Clinical Global Impression of Change (CGIc) for Narcolepsy Overall

At the end of the Double Blind Randomized Withdrawal Period, Investigators rated their impression of any change in the severity of the participant's narcolepsy overall condition since the start of the Double Blind Randomized Withdrawal Period on a 7-point scale ranging from 1 = "very much improved" to 7 = "very much worse". This endpoint measures the percentage of participants with worsening CGIc scores for narcolepsy overall, defined as scores of Much Worse or Very Much Worse.

Data from ClinicalTrials.gov

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