Pharmacokinetics of Coadministered Viloxazine Extended-Release (SPN-812) and Lisdexamfetamine in Healthy Adults. Issue 2 (March 2021)

• Record Type: Journal Article
• Authors: Faison, Shamia L.; Fry, Nicholas; Adewole, Toyin; Odebo, Oyinkansola; Wang, Zhao; Maletic, Vladimir; Nasser, Azmi
• Is Part Of: Journal of clinical psychopharmacology. Volume 41:Issue 2(2021)
• Publication Date: 2021-03
• Subjects: viloxazine -- SPN-812 -- attention-deficit/hyperactivity disorder -- lisdexamfetamine -- pharmacokinetics; Psychopharmacology -- Periodicals; Psychopharmacology -- Periodicals; Psychopharmacologie -- Périodiques; Psychopharmacology; Periodicals; 615.78
• DOI: 10.1097/JCP.0000000000001361
• Languages: English
• ISSNs: 0271-0749

Abstract

Abstract: Background: Viloxazine extended-release is a novel nonstimulant under investigation as a potential treatment for attention-deficit/hyperactivity disorder (ADHD). Given the potential for viloxazine extended-release to be co-administered with stimulant ADHD pharmacotherapies, this trial investigated the pharmacokinetics and safety of combination viloxazine extended-release + lisdexamfetamine dimesylate (lisdexamfetamine) versus viloxazine extended-release and lisdexamfetamine alone. Methods: In this single-center, cross-over, open-label trial, healthy, non-ADHD adults received single oral doses of 700 mg viloxazine extended-release alone, 50 mg lisdexamfetamine alone, and a combination of viloxazine extended-release (700 mg) + lisdexamfetamine (50 mg), with blood samples collected over 4 days postadministration. The active drug in viloxazine extended-release (viloxazine) and primary metabolite of lisdexamfetamine (D - amphetamine) were measured using chromatographic tandem mass spectrometry. Safety assessments included adverse events, vital signs, echocardiograms, and clinical laboratory evaluations. Results: Thirty-six adults were enrolled, and 34 completed the trial. The least squares geometric mean ratios are reported as [combination / single drug (90% confidence intervals)]. Viloxazine extended-release: Cmax = 95.96% (91.33–100.82), area under the concentration–time curve from 0 to the last measurable time (AUC0-t ) = 99.19% (96.53–101.91), and area under the concentration–time curve from 0 to infinity (AUCinf ) = 99.23% (96.61–101.93). Lisdexamfetamine: Cmax = 112.78% (109.93–115.71), AUC0-t = 109.64% (105.25–114.22), and AUCinf = 109.52% (105.19–114.03). All reported adverse events, except 1 (moderate vomiting), were mild in severity. Conclusions: Co-administration of viloxazine extended-release and lisdexamfetamine did not impact the pharmacokinetics of viloxazine or D - amphetamine relative to administration of either drug alone. After single dose administration, the combination appeared to be safe and well tolerated. Abstract : Supplemental digital content is available in the text.