Phase 3 Randomized Double‑Blind Placebo‑Controlled Trial of ALKS 2680 for Excessive Daytime Sleepiness in Adults with Narcolepsy Type 2

The primary objective is to assess the efficacy of ALKS 2680 in reducing excessive daytime sleepiness in adults diagnosed with Narcolepsy Type 2, addressing a core symptom that impairs daily functioning.

Secondary objectives include:

• Evaluation of ALKS 2680’s efficacy for the same primary symptom of excessive daytime sleepiness in the same patient population.
• Assessment of the drug’s impact on fatigue levels in participants with Narcolepsy Type 2.

The trial enrolled 42 participants diagnosed with Narcolepsy Type 2, aged 18 to 70 years, inclusive of both female and male individuals. Eligible subjects possessed a body mass index between 18 and 40 kg/m² and reported excessive daytime sleepiness that was inadequately controlled by prior therapies, allowing safe discontinuation and washout of those medications. Participants were required to comply with protocol‑specified lifestyle measures, including adherence to actigraphy monitoring, completion of sleep diaries, and, when applicable, maintenance of primary obstructive sleep apnea therapy for at least 30 days prior to enrollment. Additional criteria mandated the ability to provide informed consent, comply with contraception guidance, and meet investigator‑assessed suitability for study procedures.

This phase III study is a randomized, double‑blind, placebo‑controlled trial evaluating the efficacy and safety of oral ALKS 2680 tablets versus matching placebo in adults diagnosed with Narcolepsy Type 2. Eligible participants are aged 18–70 years, have a body‑mass index of 18–40 kg/m², and exhibit unsatisfactory response or intolerable side effects from prior narcolepsy therapies, with appropriate washout periods observed. The trial consists of a screening visit to confirm eligibility, obtain actigraphy and sleep‑diary data, and ensure stable management of obstructive sleep apnea if present; a baseline/randomization visit (Visit 1) where participants receive either ALKS 2680 or placebo; scheduled follow‑up visits at weeks 4, 8, and 12 for efficacy assessments (including the primary endpoint of change in Epworth Sleepiness Scale and secondary endpoints such as Maintenance of Wakefulness Test latency and patient‑reported outcomes); and an end‑of‑study visit at week 12 to finalize safety and efficacy evaluations. Participant involvement spans approximately 14 weeks, including screening and the 12‑week treatment period. Early termination may occur if a participant experiences a serious adverse event, fails to adhere to study medication or required assessments, requires prohibited concomitant therapy, withdraws consent, or if the investigator determines that continuation is not in the participant’s best interest.

The investigational product, ALKS 2680, is supplied as an oral tablet containing a dose of 00 mg of the active substance. It is administered by the oral route; the dosing frequency and schedule are specified in the study protocol and are uniform across all participants receiving the test medication.

The control arm receives a matching placebo formulated to be indistinguishable from the active tablet. The placebo contains no active pharmaceutical ingredient and is administered orally in the same tablet form and schedule as the investigational product.

All study medications are dispensed in blinded containers. Compliance is assessed by pill count at each scheduled visit and by participant dosing diaries. Administration is performed under supervision when feasible, and any missed doses are recorded in accordance with protocol‑defined procedures.

Efficacy will be assessed by measuring the change from baseline to Week 12 in the Epworth Sleepiness Scale score for each dose level. The ESS, a validated self‑administered questionnaire, will be completed by participants at screening (baseline) and at the Week 12 visit. Scores will be compared between the ALKS 2680 and placebo groups to determine the magnitude of improvement in excessive daytime sleepiness.

Secondary efficacy evaluations include the change in mean sleep latency on the Maintenance of Wakefulness Test from baseline to Week 12, measured using standard laboratory testing procedures, and the change in select patient‑reported outcome measures over the same interval. Both the MWT and the patient‑reported instruments will be administered at baseline and at Week 12, with results analyzed by dose level to assess additional aspects of treatment benefit.