OBJECTIVE: The present bioequivalence study was designed to compare the newly-developed levamlodipine besylate 2.5-mg tablet (test) with that of its 2.5-mg marketed counterpart (reference) in healthy Chinese adult male volunteers. METHODS: A single-dose, randomized, open-label, two-period, and two-treatment self-crossover study was conducted in healthy Chinese volunteers after informed consent was obtained. In each part of the study, the subjects were randomly assigned to receive the test or reference product (5 mg levamlodipine) in a 1 : 1 ratio, and then received the alternative product, following a 14-day washout period. Plasma levamlodipine concentrations were analyzed by liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters (noncompartmental model) were assessed with WinNonlin software. Analysis of variance (ANOVA) and FDA (USA) bioequivalence statistical criterion of 90% CI for 80 - 125% range (set at p ≤ 0.05) of geometric means ratios of test : reference product for C<sub>max</sub>, AUC<sub>0-t</sub>, and AUC<sub>0-∞</sub>; were determined. Tolerability was assessed during the entire study period. RESULTS: ANOVA indicated that the period, sequence, and formulation had no significant effect on the PK parameters (p ≥ 0.05), although there was a statistically-significant difference between formulations in AUC<sub>0-t</sub> (p ≤ 0.05). The test formulation was bioequivalent to the marketed formulation as the 90% CI for the ratio of geometric means of C<sub>max</sub> (84.52 - 103.00%), AUC<sub>0-t</sub> (87.49 - 98.23%), and AUC<sub>0-∞</sub> (84.30 - 103.25%) were within equivalence limits (80 - 125%) under fasting condition. No serious adverse events were found among the subjects. CONCLUSION: This study confirmed that test and reference levamlodipine besylate tablets were bioequivalent under fasting condition. .
RCT Entities:
OBJECTIVE: The present bioequivalence study was designed to compare the newly-developed levamlodipine besylate 2.5-mg tablet (test) with that of its 2.5-mg marketed counterpart (reference) in healthy Chinese adult male volunteers. METHODS: A single-dose, randomized, open-label, two-period, and two-treatment self-crossover study was conducted in healthy Chinese volunteers after informed consent was obtained. In each part of the study, the subjects were randomly assigned to receive the test or reference product (5 mg levamlodipine) in a 1 : 1 ratio, and then received the alternative product, following a 14-day washout period. Plasma levamlodipine concentrations were analyzed by liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters (noncompartmental model) were assessed with WinNonlin software. Analysis of variance (ANOVA) and FDA (USA) bioequivalence statistical criterion of 90% CI for 80 - 125% range (set at p ≤ 0.05) of geometric means ratios of test : reference product for C<sub>max</sub>, AUC<sub>0-t</sub>, and AUC<sub>0-∞</sub> were determined. Tolerability was assessed during the entire study period. RESULTS: ANOVA indicated that the period, sequence, and formulation had no significant effect on the PK parameters (p ≥ 0.05), although there was a statistically-significant difference between formulations in AUC<sub>0-t</sub> (p ≤ 0.05). The test formulation was bioequivalent to the marketed formulation as the 90% CI for the ratio of geometric means of C<sub>max</sub> (84.52 - 103.00%), AUC<sub>0-t</sub> (87.49 - 98.23%), and AUC<sub>0-∞</sub> (84.30 - 103.25%) were within equivalence limits (80 - 125%) under fasting condition. No serious adverse events were found among the subjects. CONCLUSION: This study confirmed that test and reference levamlodipine besylate tablets were bioequivalent under fasting condition. .