Objective:

To present the results from a randomized, double-blind, phase 1b study assessing the safety, tolerability, and pharmacodynamics of ALKS 2680 in patients with narcolepsy type 1 (NT1).

Background:

ALKS 2680 is a potent, centrally active, orally bioavailable, and highly selective orexin 2 receptor agonist being developed for the once-daily treatment of narcolepsy and idiopathic hypersomnia.

Design/Methods:

Patients with NT1 received single doses of 1, 3, and 8 mg ALKS 2680 and matching placebo in a 4-way randomized crossover design following 2-week washout of their current narcolepsy treatments. Safety assessments included adverse events (AEs), vital signs, clinical laboratory assessments, and electrocardiograms (ECG). Pharmacodynamic efficacy assessments included the Maintenance of Wakefulness Test (MWT) and the Karolinska Sleepiness Scale (KSS).

Results:

In patients with NT1 (N=10), there were no serious or severe AEs; no patient discontinued due to any AE. AEs related to study drug and occurring in >1 patient were insomnia, pollakiuria, salivary hypersecretion, decreased appetite, dizziness, and nausea. No drug-related, treatment-emergent, clinically meaningful changes from baseline were identified in laboratory values, vital signs, or ECGs. On the MWT, ALKS 2680 increased mean sleep latency, demonstrating placebo-corrected changes from baseline of 18.4 minutes (1 mg), 22.6 minutes (3 mg), and 34.0 minutes (8 mg) through 8 hours post-dose (p<0.001 for each dose vs placebo). On the KSS, ALKS 2680 showed clinically meaningful, dose-dependent improvements of 2-3 points in self-reported alertness between 1 and 8 hours (p<0.001 for each dose vs placebo).

Conclusions:

ALKS 2680 was generally well-tolerated. Single doses up to 8 mg led to statistically significant, clinically meaningful improvements in sleep latency and patient-reported alertness and support further clinical evaluation of ALKS 2680 in phase 2.