Pharmacokinetics of ADS-5102 (Amantadine) Extended Release Capsules Administered Once Daily at Bedtime for the Treatment of Dyskinesia

Clinical Pharmacokinetics
Robert A HauserGregory T Went

Abstract

Preclinical and clinical studies suggest amantadine immediate-release (IR) may reduce dyskinesia in Parkinson's disease (PD), although higher doses are associated with increased CNS adverse events (AEs). ADS-5102 is an extended release amantadine capsule formulation, designed for once-daily dosing at bedtime (qhs) to provide high concentrations upon waking and throughout the day, with lower concentrations in the evening. The pharmacokinetics (PK) of ADS-5102 were assessed in two phase I studies in healthy subjects, and a blinded, randomized phase II/III dose-finding study in PD patients. The first phase I study assessed single ADS-5102 doses (68.5, 137, and 274 mg) in a crossover design, whereas the second phase I study evaluated ADS-5102 137 mg for 7 days followed by amantadine IR 81 mg twice daily (or reverse order). In the phase II/III double-blind study, PD patients with dyskinesia were randomized to ADS-5102 (210, 274, or 338 mg) or placebo for 8 weeks. Single ADS-5102 doses resulted in a slow initial rise in amantadine plasma concentration, with delayed time to maximum concentration (12-16 h). Amantadine plasma concentrations were higher in PD patients versus healthy volunteers. The steady-state profile of once-daily ADS-...Continue Reading

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Citations

May 22, 2018·Movement Disorders Clinical Practice·Stuart H IsaacsonReed Johnson
May 7, 2019·Expert Opinion on Pharmacotherapy·Thomas MüllerJan-Dominique Möhr
Jul 25, 2019·Drugs·Thomas Müller, Jan-Dominique Möhr
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Feb 25, 2021·Journal of Neural Transmission·Wojciech DanyszPeter Riederer
Jul 6, 2021·Aging and Disease·Dipali NemadeVikram Shivkumar
Dec 18, 2021·Neurodegenerative Disease Management·Thomas Müller

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