The Orexin 2 Receptor Agonist ALKS 2680 in Patients With Narcolepsy Type 2: An Initial Proof of Concept Phase 1b Study
Introduction: 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. Safety and pharmacodynamic results from a phase 1b study in patients with narcolepsy type 2 (NT2) are presented.
Methods: Patients with NT2 received single doses of 5, 12, and 25 mg ALKS 2680 and matching placebo in a 4-way randomized crossover design. Safety assessments included adverse events (AEs), vital signs, clinical laboratory assessments, and electrocardiograms (ECG). Efficacy assessment was mean sleep latency on the Maintenance of Wakefulness Test (MWT).
Results: In patients with NT2 (Nf9), there were no serious AEs; no patient discontinued due to any AE. AEs related to study drug (>1 patient) were pollakiuria, insomnia, and dizziness. All AEs were mild except 1 case of moderate pollakiuria. No 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 versus placebo over 8 hours post-dose, as assessed by estimated least square mean difference in change from baseline, by 11.6 minutes (5 mg, p < 0.05), 18.6 minutes (12 mg, p < 0.001), and 21.0 minutes (25 mg, p < 0.001). Observed mean sleep latencies at 12 and 25 mg were >30 minutes over 8 hours.
Conclusions: ALKS 2680 was generally well-tolerated among patients with NT2. Single doses of ALKS 2680 at 5, 12, and 25 mg led to statistically significant, clinically meaningful sleep latency improvements and support further clinical evaluation of ALKS 2680 in phase 2.
