کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6790700 | 1432679 | 2018 | 13 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
The safety, tolerability and pharmacokinetics of BI 409306, a novel and potent PDE9 inhibitor: Overview of three Phase I randomised trials in healthy volunteers
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
روانپزشکی بیولوژیکی
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چکیده انگلیسی
Safety, tolerability and pharmacokinetics of BI 409306, a potent and selective phosphodiesterase 9A inhibitor, were assessed in healthy subjects in three Phase I, within-dose group, double-blind trials. Trial 1 randomised young and elderly subjects to receive BI 409306 25, 50, 100â¯mg, placebo once daily (OD) or BI 409306 50â¯mg twice daily (young) for 14 days. Trial 2 randomised young poor metabolisers (PM) of cytochrome P450 isoform 2C19 (CYP2C19) and elderly subjects to receive BI 409306 25, 50â¯mg or placebo OD for 14 days. Trial 3 randomised Chinese and Japanese extensive metabolisers of CYP2C19 to receive single doses (SD) of BI 409306 25, 50, 100â¯mg or placebo and Chinese (PM) to SD of BI 409306 100â¯mg or placebo (Part 1). Japanese PM received SD of BI 409306 100â¯mg or placebo (Day 1) followed by BI 409306 100â¯mg or placebo OD for 7 days after a 48-hour washout period (Part 2). Reported adverse events (AE) were mild-to-moderate intensity and increased with BI 409306 dose. Eye disorders were most commonly reported (Trial 1: 40.0-41.7%, Trial 2: 29.2-37.5%, Trial 3: 18.2-66.7%) and increased with dose and systemic exposure. PM reported more AEs than other treatment groups, corresponding to higher systemic exposure to BI 409306. Systemic exposure to BI 409306 produced dose-dependent increases and was slightly greater in elderly versus young subgroups (Trial 1). Steady state was achieved by Day 2-3. Overall, BI 409306 demonstrated good safety, tolerability and minor accumulation after multiple dosing.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Neuropsychopharmacology - Volume 28, Issue 5, May 2018, Pages 643-655
Journal: European Neuropsychopharmacology - Volume 28, Issue 5, May 2018, Pages 643-655
نویسندگان
Viktoria Moschetti, Maria Kim, Michael Sand, Glen Wunderlich, Grit Andersen, Ulrich Feifel, In-Jin Jang, Wolfgang Timmer, Holger Rosenbrock, Katja Boland,