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 with narcolepsy type 1, addressing a core symptom that significantly impairs daily functioning and safety.

Secondary objectives include:

• Evaluation of ALKS 2680’s effect on cataplexy frequency and severity in the same population.
• Assessment of the impact of ALKS 2680 on patient‑reported fatigue levels.

The trial enrolled 63 participants diagnosed with Narcolepsy Type 1, a rare disorder characterized by excessive daytime sleepiness. Eligible individuals were adults aged 18 to 70 years, of any gender, with a body mass index between 18 and 40 kg/m². Inclusion required an unsatisfactory clinical response or intolerable side effects from current narcolepsy medications, the ability to discontinue such therapies during the study, and compliance with washout periods. Participants needed to consent to protocol requirements, including lifestyle restrictions, contraception guidance, and the use of actigraphy, cataplexy, and sleep diaries. Subjects receiving treatment for obstructive sleep apnea were required to maintain adherence to their primary therapy for at least 30 days prior to enrollment and throughout the study. The population comprised both female and male patients, and vulnerable individuals were not excluded.

The study is a Phase III, randomized, double-blind, placebo-controlled trial evaluating the efficacy and safety of ALKS 2680 in adults with narcolepsy type 1. After an initial screening visit to confirm eligibility, participants are randomized to receive either ALKS 2680 tablets or matching placebo for a 12‑week treatment period. Study visits are scheduled at baseline (Day 1) and at Weeks 4, 8, and 12 to assess efficacy endpoints, including change from baseline in the Epworth Sleepiness Scale, and safety parameters. The end‑of‑study visit occurs at Week 12, with a final follow‑up to capture any late‑onset adverse events. Total participant involvement spans approximately 14 weeks, including screening, treatment, and follow‑up. Participants may be withdrawn early for reasons such as medically significant adverse events, non‑compliance with study procedures, use of prohibited concomitant medication, or voluntary withdrawal of consent.

The investigational product, ALKS 2680, is supplied as an oral tablet containing 00 mg of the active substance per tablet. The tablets are administered by the oral route; the specific dosing schedule and frequency are defined in the study protocol and are consistent across participants receiving the test medication.

Placebo tablets are formulated to match the appearance of ALKS 2680 tablets. Two matching placebos are used: one matched to ALKS 2680 and another matched to ALKS 2680/Alixorexton. These inert tablets contain no active pharmaceutical ingredient and are administered orally in the same manner as the active drug.

All study medications are dispensed in blister packs to facilitate compliance monitoring. Participants are instructed to record each dose in a medication diary, and pill counts are performed at each study visit to assess adherence. Administration occurs under double‑blind conditions, ensuring that participants, investigators, and study staff remain unaware of treatment allocation.

This trial evaluates the efficacy and safety of ALKS 2680 for the treatment of excessive daytime sleepiness in adults diagnosed with Narcolepsy Type 1. Standard procedures for dosing, administration, and compliance verification are applied uniformly to both the investigational product and placebo arms.

Efficacy will be assessed primarily by the change in Epworth Sleepiness Scale score from baseline to Week 12, evaluated for each dose level. The scale is administered at screening, baseline, and Week 12 to quantify excessive daytime sleepiness.

Secondary efficacy assessments include: the change in mean sleep latency on the Maintenance of Wakefulness Test from baseline to Week 12; the weekly cataplexy rate measured at Week 12; and the change in selected patient-reported outcome measures from baseline to Week 12. Sleep latency is determined using standardized laboratory testing at baseline and Week 12. Cataplexy frequency is captured via weekly diaries, and patient-reported outcomes are collected using validated questionnaires at the same time points. All efficacy parameters will be analyzed by comparing each active dose group to placebo, using appropriate statistical methods for change from baseline.