Phase 3 Randomized Double‑Blind Placebo‑Controlled Trial of ALKS 2680 for Excessive Daytime Sleepiness in Adults with Narcolepsy Type 1

The primary objective is to assess the efficacy of ALKS 2680 in reducing excessive daytime sleepiness in adults diagnosed with Narcolepsy Type 1, addressing a core symptom that impairs daily functioning. Secondary objectives include:

• Evaluation of ALKS 2680’s efficacy for the treatment of excessive daytime sleepiness in this population.
• Evaluation of ALKS 2680’s efficacy for the treatment of cataplexy.
• Evaluation of the effects of ALKS 2680 on fatigue.

The trial enrolled 22 participants diagnosed with Narcolepsy Type 1, aged 18 to 70 years, including both female and male adults. Eligible individuals were required to have a body mass index between 18 and 40 kg/m² and to be experiencing unsatisfactory clinical response or side effects from existing narcolepsy medications, allowing safe discontinuation of those agents during the study. Participants had to provide informed consent, comply with protocol‑specified lifestyle restrictions, and adhere to contraception guidance. Additional requirements included the ability to complete actigraphy, cataplexy, and sleep diaries, and, if applicable, maintain consistent therapy for obstructive sleep apnea throughout the study. The selection process focused on patients meeting these criteria, ensuring a population representative of adults with inadequate control of excessive daytime sleepiness due to Narcolepsy Type 1.

The study is a Phase III, randomized, double‑blind, placebo‑controlled trial evaluating the efficacy and safety of oral ALKS 2680 in adults diagnosed with Narcolepsy Type 1. After an initial screening visit to confirm eligibility, obtain baseline measurements, and collect actigraphy, cataplexy, and sleep diaries, eligible participants are assigned in a 1:1 ratio to receive either ALKS 2680 or a matching placebo for a 12‑week treatment period. Follow‑up visits are scheduled at Week 4, Week 8, and Week 12 to assess safety, tolerability, and efficacy, with the primary efficacy endpoint being the change from baseline to Week 12 in the Epworth Sleepiness Scale. Secondary assessments include mean sleep latency on the Maintenance of Wakefulness Test, weekly cataplexy rate, and selected patient‑reported outcomes. The end‑of‑study visit at Week 12 completes the final evaluations and discontinuation of study medication. Participant involvement spans approximately 14 weeks, encompassing screening, the 12‑week treatment phase, and the concluding visit.

The investigational product, ALKS 2680, is provided in tablet form for oral administration. Each tablet contains a dose of 0 mg as specified in the study protocol. The tablets are supplied for use throughout the double‑blind treatment period.

The control arm receives a matching Placebo tablet designed to be indistinguishable from the active tablets in appearance and administration characteristics. No active pharmaceutical ingredients are present in the placebo formulation.

All study medications are taken orally according to the schedule defined in the protocol, with adherence assessed by pill count at each study visit and documented in the electronic case report form. Participants are instructed to maintain a medication diary to record each dose taken, and compliance is reviewed by study staff during scheduled assessments. The trial enrolls adults diagnosed with narcolepsy type 1 who experience excessive daytime sleepiness, and the primary objective is to evaluate the efficacy and safety of the investigational product in this population.

The primary efficacy assessment is the change in the Epworth Sleepiness Scale score from baseline to Week 12, measured using the validated questionnaire at the baseline visit and at the Week 12 visit for each dose group.

Secondary efficacy evaluations include the change in mean sleep latency on the Maintenance of Wakefulness Test from baseline to Week 12, the weekly cataplexy rate at Week 12, and the change in selected patient‑reported outcome measures from baseline to Week 12. The Maintenance of Wakefulness Test is performed under standardized laboratory conditions at baseline and Week 12 to determine mean sleep latency. Weekly cataplexy episodes are recorded by participants in a diary throughout the treatment period and summarized for the Week 12 interval. Patient‑reported outcomes are collected using study‑specified questionnaires at baseline and at the end of the 12‑week treatment period. All efficacy parameters are analyzed by dose level using appropriate statistical methods to compare changes from baseline.