Investigation of bioequivalence, safety, and tolerability of a fixed-dose combination of nifedipine GITS and candesartan compared with the corresponding loose-dose combination under fed conditions
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To investigate the bioequivalence, safety, and tolerability of single-dose nifedipine gastrointestinal therapeutic system (GITS) and candesartan as a fixed-dose combination (FDC) relative to the loose combination in healthy males under fed conditions.A total of 48 subjects received nifedipine GITS 60 mg and candesartan 32 mg as an FDC or loose combination in an open-label, 2-way crossover, 2-treatment sequence design, with a washout of at least 5 days between treatments. Study medications were administered following an overnight fast of at least 10 hours, and 30 minutes after ingestion of a high-fat test meal. Plasma samples were collected at intervals over a 48-hour period post-dosing. Safety and tolerability parameters were documented throughout the study.For nifedipine, 90% confidence intervals (CIs) for the ratios of FDC/loose combination were within acceptance limits of bioequivalence (i.e., 80 - 125%) for both AUC (91.36%; 111.5%) and C (87.93%; 100.5%). For candesartan, 90% CIs for the ratios of FDC/loose combination were within acceptance limits for AUC (112.8%; 124.4%), but not for C (120.5%; 137.8%). There were no serious adverse events (AEs) or AEs leading to treatment discontinuation and no clinically relevant changes in vital signs or laboratory parameters.A single dose of the FDC-containing nifedipine GITS 60 mg and candesartan 32 mg, when compared to the corresponding loose combination under fed conditions, met the criterion for bioequivalence based on AUC, while the slightly higher C for candesartan is not considered clinically relevant. The FDC displayed safety and tolerability profiles similar to the loose combination.