0612 Evaluation of Abuse Potential of the Narcolepsy Medication Pitolisant

Introduction All medications currently approved by the US FDA for the treatment of narcolepsy are controlled substances. Pitolisant, a histamine 3 (H3)-receptor antagonist/inverse agonist, is approved in Europe for the treatment of narcolepsy with or without cataplexy in adults. Methods This randomized, double-blind, active- and placebo-controlled, single-dummy, 4-sequence 4-way crossover study evaluated the abuse potential of single-dose pitolisant (35.6 mg [therapeutic dose] and 213.6 mg [supratherapeutic dose]) compared with the stimulant phentermine HCl (60 mg; a Schedule IV controlled substance) and placebo in nondependent recreational stimulant users. The primary endpoint was peak effect (Emax) for Drug Liking “at this moment” on a bipolar visual analogue scale (0=strong disliking, 100=strong liking). Key secondary endpoints included Overall Drug Liking and willingness to Take Drug Again. Between-treatment comparisons were analyzed using a mixed-effect model for a crossover study. Results After confirming their ability to discriminate phentermine (active control) from placebo, 43 participants were randomly assigned to 1 of 4 treatment sequences. For 38 participants who completed the study (73.7% male; 65.8% white; mean age, 33.3 years), mean (SE) Drug Liking Emax was 78.7 (2.8), 59.0 (2.1), 57.3 (2.1), and 56.1 (2.1), respectively, for phentermine, pitolisant 213.6 mg, pitolisant 35.6 mg, and placebo. Mean Drug Liking Emax was significantly greater for phentermine compared with placebo (P