Evaluation of Pharmacokinetics, Safety and Tolerability of Single and Multiple Oral Doses of Neramexane Mesylate in Healthy Japanese Subjects

Summary

Part 1 (single dose) Primary parameters * Area under the plasma concentration curve from zero to infinity \[AUC0-inf\] and observed maximum plasma concentration \[Cmax\] of Japanese and Caucasian subjects for each dose group * If at least 20% of the Japanese or of the Caucasian subjects have an area under the plasma concentration curve extrapolation \[AUCextrap%\] \>20% relative to AUC0-inf for one of the dose groups area under the plasma concentration curve from zero to the last measurable concentration \[AUC0- tz\] becomes primary parameter for Japanese and Caucasian subjects for all of the dose groups. In this case AUC0-tau will become a secondary parameter Secondary parameters and derived values from statistical analysis * Dose proportionality and linearity in Japanese subjects * Ratios (Japanese vs. Caucasian subjects) of AUC0-∞ and Cmax for each dose group * Dose normalized AUC \[AUC0-inf,norm\], dose normalized Cmax \[Cmax,norm\], AUC0- tz, time of occurrence of Cmax \[tmax\], apparent terminal half life \[t½\], mean residence time \[MRT\], apparent (oral) total plasma clearance \[CLtot/f\], apparent volume of distribution during the terminal disposition phase \[Vz/f\], AUCextrap%, apparent terminal disposition rate constant \[λz\], weight corrected AUC0-inf, weight corrected AUC0-tz, weight corrected Cmax, weight corrected CLtot/f, cumulative amount of excreted Neramexane into urine \[Ae0-tz\], fraction of orally administrated drug excreted into urine \[fe/f\], renal clearance \[CLR\] and apparent non-renal clearance \[CLNR/f\] * Safety and tolerability Other parameters * Pharmacogenetics * Amount of N-OH Neramexane excreted in urine \[Ae0-tz\] if a validated method will be available at the time of analysis * Metabolite determination (N-OH Neramexane) in plasma and urine, optional (may be analyzed and evaluated if a validated method will be available at the time of analysis) * Endogenous creatinine clearance \[CLCR\], amount of excreted creatinine into urine per hour \[AeCR,hr\] * Evaluation of further metabolites will be described in detail in the Statistical Analysis Plan

Timeline

Start

2009-09

Primary completion

2010-09

Completion

2010-09

Drugs

Indications

No indication recorded.