A Phase 3 Study to Evaluate the Efficacy and Safety of Samelisant in Patients With Narcolepsy (AWAKE)

A Phase 3, Double-blind, Placebo-controlled, Parallel-group, Multicenter Study to Evaluate the Efficacy and Safety of Samelisant Compared to Placebo in Patients With Narcolepsy With or Without Cataplexy

The primary objective of this study is to evaluate the effect of Samelisant on excessive daytime sleepiness (EDS) after 12 weeks of treatment. In addition, the study aims to assess its effectiveness in influencing the weekly frequency of cataplexy episodes (sudden bouts of muscle weakness) that occur while the individual remains conscious. Other objectives include examining the impact of Samelisant on attention and alertness, overall quality of life, the spectrum of narcolepsy symptoms, and daily functioning, as well as evaluating its safety profile.

This is a Phase 3, randomized, double-blind, placebo-controlled, parallel-group, multicenter study to evaluate the efficacy and safety of Samelisant compared to placebo in the treatment of excessive daytime sleepiness in male or female participants ≥18 years of age with narcolepsy with and without cataplexy.

Participants will be randomized to receive either Samelisant or matching placebo tablets for duration of 12 weeks. Treatment allocation will remain blinded to both participants and investigators throughout the study, except in cases of medical necessity.

Key Inclusion Criteria:

1. Body mass index ranging from 18 to 45 kg/m2 (both inclusive).
2. Narcolepsy with or without cataplexy (Narcolepsy Type 1 [NT1] or Narcolepsy Type 2 [NT2]) based on the International Classification of Sleep Disorders 3-TR/ Diagnostic and Statistical Manual of Mental Disorders (DSM-5-TR) criteria for the diagnosis of narcolepsy.
3. For NT1 only, current continuing presence of cataplexy as defined by participant report for the last 3 months and have average of ≥4 weekly cataplexy events during the last 2 weeks of the washout period.
4. At the screening Visit and the Baseline Visit, participants who are not on treatment for EDS must have ESS scores ≥12 (as assessed with a look-back period of 1 week).
5. A mean MWT time of <12 minutes across the first 4 sessions at Baseline.
6. Willingness to complete the study protocol with full compliance with procedures and sign an informed consent form.
7. Able to show compliance with sleep diary entries for at least 5 times/week in the final 2 weeks of the screening Period (non-compliant participants will not be included).

Key Exclusion Criteria:

1. Median habitual wake-up time after 9 am as assessed by sleep diary, habitual sleep time of <6 h and median habitual bedtime past 1 am, as determined by sleep diary entries.
2. Use of any investigational therapy within the 30-day period (or 5 half-lives, whichever is longer) prior to enrollment.
3. History of (within past 3 months) or current substance use disorder involving illicit drugs, alcohol, or marijuana, as per DSM-5-TR criteria. Alcohol and/or recreational drugs use within 24 hours of study visits is strictly prohibited.
4. Excessive caffeine (defined as >600 mg/day) use at least 1 week prior to Baseline assessments and during the study.
5. Nicotine dependence that affects sleep (eg, a participant who routinely awakens at night to smoke).
6. If receiving stimulants, modafinil, oxybates, pitolisant, solriamfetol, bupropion or other treatments for narcolepsy, and unwilling or unable to complete weaning 2 weeks prior to Baseline visit (Day 1)
7. Clinically significant ECG abnormalities. Participants are excluded with a screening ECG Fridericia's correction of QT (QTcF) interval ≥450 msec for men and ≥470 msec for women obtained after 5-minute rest in a supine position using a digital ECG.
8. Concurrent use of hypnotics, tranquilizers, centrally acting H1 receptor antagonists, benzodiazepines, anticonvulsants, or clonidine, tricyclic antidepressants that have H1-antihistamine properties (clomipramine, protriptyline).
9. Adjunctive pharmacotherapy directed against cataplexy (including but not limited to venlafaxine, fluoxetine, and gamma hydroxybutyrate) is prohibited.
10. An occupation requiring variable shift work, variable wake times, night shifts, frequent overnight travel or expected overnight travel across > 3 time zones during the study which disrupts sleep patterns and working remotely leading to inconsistent sleep duration.