Dataset Information

Safety and Pharmacokinetics of High-Dose TAS-303 in Healthy Japanese Volunteers: A Single-Center, Single-Blind, Randomized, Placebo-Controlled, Parallel-Group, Multiple-Ascending-Dose Study.

ABSTRACT: Preclinical data of TAS-303 (4-piperidinyl 2,2-diphenyl-2-[propoxy-1,1,2,2,3,3,3-d7 ] acetate hydrochloride), a noradrenaline reuptake inhibitor, show that it increases urethral contraction in rats and may therefore benefit stress urinary incontinence patients. In this single-blind, randomized, placebo-controlled, parallel-group, multiple-ascending-dose phase 1 study, we evaluated the safety and tolerability of once-daily TAS-303 8, 10, 12, 15, or 18 mg administered for 16 days in healthy subjects. In addition, we investigated the pharmacokinetics and inhibitory effect of TAS-303 on hepatic cytochrome P450 (CYP) 3A activity. Rates of adverse events, adverse drug reactions, and pharmacokinetic parameters of TAS-303 were evaluated. Fifty subjects were randomized: 7 subjects each were assigned to receive TAS-303 8-18 mg, and 3 subjects each were assigned to receive placebo at each dose. The overall incidences of adverse events and adverse drug reactions in all subjects administered TAS-303 (n = 35) was 25.7% and 2.9%, respectively, and those for the placebo groups (n = 15) were 46.7% and 0%, respectively. No deaths or serious adverse events occurred. TAS-303 displayed a dose-proportional pharmacokinetic profile across doses of 8-18 mg over the 16-day multiple administration period, and TAS-303 might inhibit hepatic CYP3A activity within this dose range. TAS-303 at a dose of 8-18 mg was confirmed to be safe and tolerable.

SUBMITTER: Hanada R

PROVIDER: S-EPMC7687182 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Safety and Pharmacokinetics of High-Dose TAS-303 in Healthy Japanese Volunteers: A Single-Center, Single-Blind, Randomized, Placebo-Controlled, Parallel-Group, Multiple-Ascending-Dose Study.

Hanada Ryuzo R

Clinical pharmacology in drug development 20200623 8

Preclinical data of TAS-303 (4-piperidinyl 2,2-diphenyl-2-[propoxy-1,1,2,2,3,3,3-d<sub>7</sub> ] acetate hydrochloride), a noradrenaline reuptake inhibitor, show that it increases urethral contraction in rats and may therefore benefit stress urinary incontinence patients. In this single-blind, randomized, placebo-controlled, parallel-group, multiple-ascending-dose phase 1 study, we evaluated the safety and tolerability of once-daily TAS-303 8, 10, 12, 15, or 18 mg administered for 16 days in hea ...[more]

PMID: 32573956

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Dataset Information

Safety and Pharmacokinetics of High-Dose TAS-303 in Healthy Japanese Volunteers: A Single-Center, Single-Blind, Randomized, Placebo-Controlled, Parallel-Group, Multiple-Ascending-Dose Study.

Publications

Safety and Pharmacokinetics of High-Dose TAS-303 in Healthy Japanese Volunteers: A Single-Center, Single-Blind, Randomized, Placebo-Controlled, Parallel-Group, Multiple-Ascending-Dose Study.

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