10 Pharmacodynamics and Tolerability of Intranasally Administered Immediate-Release Amphetamine Sulfate Among Recreational Intranasal StimulantUsers. (12th March 2019)

• Record Type: Journal Article
• Authors: Setnik, Beatrice; Caras, Steve; Sharpe, Terrilyn; Faraone, Stephen V.
• Is Part Of: CNS spectrums. Volume 24:Number 1(2019:Feb)
• Page Start: 178
• Page End: 178
• Publication Date: 2019-03-12
• Subjects: Neuropsychiatry -- Periodicals; Nervous system -- Diseases -- Periodicals; Neurology -- Periodicals; 616.8005
• DOI: 10.1017/S1092852919000063
• Languages: English
• ISSNs: 1092-8529

Abstract

Abstract: Study Objective: Despite increased nonmedical use of ADHD prescription stimulants, there are limited data to inform selection of intranasal doses for abuse-potential evaluations. This study determined a dose of amphetamine sulfate that is tolerable and distinguishable from placebo on pharmacodynamic (PD) measures. Methods: In this randomized, double-blind, placebo-controlled, dose-escalation study, healthy, nondependent, recreational stimulant users received a single intranasal dose of amphetamine sulfate (20, 30, or 40mg ; n=6 per group) or placebo (n=2 per group). PD and safety were assessed pre-dose and ≤24hours post-dose. Drug Liking was measured using a bipolar Visual Analogue Scale (VAS; 0–100). Dose selection criteria were complete dose insufflation (≥95%); demonstration of peak Drug Liking ≥75 points, and ≥15 points greater than placebo in ≥3 participants receiving active drug; and tolerability. Results: Peak Drug Liking criteria were met in the 20-, 30-, and 40-mg groups by 2, 0, and 6 participants, respectively. Mean (SD) peak Drug Liking was 62 (13.0), 71 (17.8), and 93 (8.7) for amphetamine sulfate versus 54 (3.5), 76 (34.6), and 51 (0) for placebo in the 20-, 30-, and 40-mg groups, respectively. Thirteen participants experienced mild AEs (n=1, 4, 6, and 1 in 20-, 30-, 40-mg, and placebo groups, respectively), there were no serious or clinically significant AEs. The most common AE was nostril burning sensation (active drug, n=7). There were no instances of an incompletely insufflateddose. Conclusion: A 40-mg intranasal dose produced distinguishable PD effects and was well tolerated. This dose has been selected for further abuse-potential evaluations. Funding Acknowledgements: This study was funded by Arbor Pharmaceuticals, LLC.