Pharmacokinetic properties and safety assessment of the generic vaginal gel progesterone preparation: results of an open-label, randomized, crossover bioequivalence study

Objective: To assess bioequivalence of the generic (test) progesterone preparation Miragel, vaginal gel 90 mg/ dose (WERTEX JSC, Russia) and the branded (reference) vaginal gel progesterone Crinone, 90 mg/dose (Merck Serono Limited, Great Britain). Materials and methods: Progesterone concentrations in the blood plasma of volunteers (naturally postmenopausal women) were determined after a single intravaginal injection of the generic Miragel, vaginal gel 90 mg/dose (WERTEX JSC, Russia) and branded preparation Crinone, vaginal gel 90 mg/dose (Merck Serono Limited, Great Britain). The study was conducted using an open-label, randomized, a 4-period crossover scheme, with two sequences of medicine administration and with an interval of 14 days. A total of 42 female volunteers who met the inclusion and non-inclusion criteria were selected for participation in the study; all of them provided informed consent. The concentration of progesterone in the blood plasma samples of volunteers was determined using high performance liquid chromatography tandem mass spectrometry. Results: Progesterone concentration was identif ied in 3281blood plasma samples obtained from 42 volunteers during four study periods. The mean values and standard deviations of the pharmacokinetic parameters of progesterone after intravaginal administration of the test and reference drugs were as follows: C 11.497+3.693 ng/ml and 10.912±3.651 ng/ml; AUC0I 200.114+93.023 ng-h/ml and 225.264+134.477ngh/ml, respectively. Two-sided 90% confidence intervals for the ratios of the corresponding geometric mean values of the pharmacokinetic parameters of progesterone Cmax and AUC0 t were 100.45-111.98% and 85.28-101.41%, respectively. A total of 30 adverse events were registered in 20 volunteers of the safety population (47.6%): 18 adverse events in 14 volunteers (33.3%) after administration of the test drug and 12 adverse events in 10 volunteers (23.8%) after administration of the reference drug. No adverse events that would be reliably, probably or possibly associated with the administration of the test or reference preparations have been registered. Conclusion: The boundaries of the estimated two-sided 90% confidence intervals for the ratio of the geometric mean values of the pharmacokinetic parameters AUC0 I and Cmax range from 80.00 to 125.00%. Therefore, the test preparation Miragel, vaginal gel 90 mg/dose (WERTEX JSC, Russia) and the reference drug Crinone, vaginal gel 90 mg/dose (Merck Serono Limited, Great Britain), are bioequivalent.

progesterone, vaginal gel, generic drug, reference drug, bioequivalence study