Evaluation of pharmacokinetics and safety with bioequivalence of Amlodipine in healthy Chinese volunteers: Bioequivalence Study Findings

Background and objective: Amlodipine, a main series of L-type calcium channel blockers (CCBs), exerts potent antihypertensive effects. The aim of this trial was to explore the pharmacokinetics (PK) and safety with bioequivalence of orally administered Amlodipine provided by two sponsors in healthy volunteers (HVs).

Methods: Two separate randomized, open-label, single-dose, crossover-design studies were conducted: a fasting study (n = 24) and a fed study (n = 24). In each study, HVs were randomized to Fangming Pharmaceutical Group (Test, T) followed by NORVASC^® (Reference, R), or vice versa. Each study subject received a 5-mg Amlodipine tablet with a 15-day washout. The plasma concentrations of Amlodipine were measured using a LC-MS/MS method, and PK parameters were determined by noncompartmental model.

Results: Forty-eight healthy volunteers were enrolled. And overall demographics were as follows: the fasting study: female (n = 16/24), age (18-54 years), weight (47-76 kg), and BMI (19.5-26.0). The fed study: female (n = 16/24), age (20-49 years), weight (45.5-69 kg), and BMI (19.1-25.0). All PK endpoints met the pre-specific criteria for PK equivalence. In fasting subjects, the maximum plasma concentration (C_max ) was 3.881 ± 0.982 ng/mL at 6 hours (median) of sponsor T, and 4.042 ± 1.147 ng/mL at 6 hours (median) of sponsor R. In fed subjects, C_max was 3.312 ± 0.789 ng/mL at 6 hours (median) of sponsor T, and 3.392 ± 0.902 ng/mL at 5 hours (median) of sponsor R. Both fasting and fed studies achieved a plausible bioequivalence.

Conclusions: Amlodipine is well tolerated and have a favorable safety profile. The observed adverse events were mild (the severity was assessed according to the Common Terminology Criteria for Adverse Events [version CTCAE4.03]) and all of them were recovered without severe sequences. And the bioequivalence is achieved under fasting and fed conditions, supporting the demonstration of biosimilarity.