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

Inclusion criteria

• Body mass index ranging from 18 to 45 kg/m2 (both inclusive).
• 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.
• 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.
• 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).
• A mean MWT time of \<12 minutes across the first 4 sessions at Baseline.
• Willingness to complete the study protocol with full compliance with procedures and sign an informed consent form.
• 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

• 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.
• Use of any investigational therapy within the 30-day period (or 5 half-lives, whichever is longer) prior to enrollment.
• 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.
• Excessive caffeine (defined as \>600 mg/day) use at least 1 week prior to Baseline assessments and during the study.
• Nicotine dependence that affects sleep (eg, a participant who routinely awakens at night to smoke).
• 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)
• 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.
• Concurrent use of hypnotics, tranquilizers, centrally acting H1 receptor antagonists, benzodiazepines, anticonvulsants, or clonidine, tricyclic antidepressants that have H1-antihistamine properties (clomipramine, protriptyline).
• Adjunctive pharmacotherapy directed against cataplexy (including but not limited to venlafaxine, fluoxetine, and gamma hydroxybutyrate) is prohibited.
• 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.