This clinical trial evaluated the comparative bioavailability of two injectable suspension formulations of medroxyprogesterone acetate + estradiol cypionate, a test (Depomês®, 25 mg/mL medroxyprogesterone acetate + 5 mg/mL estradiol cypionate, Biolab Sanus Farmacêutica Ltda.) and a reference formulation (Cyclofemina®, 25 mg/0.5 mL medroxyprogesterone acetate + 5 mg/0.5 mL estradiol cypionate, Millet Roux Ltda.) in healthy female volunteers after a single intramuscular dose administration. In addition, this study also evaluated the safety and tolerability of these drugs.
This study was performed in a monocentric, open label, parallel design, with 2 treatments, 1 period, in which twelve subjects received the test product (Depomês®, 25 mg/mL medroxyprogesterone acetate + 5 mg/mL estradiol cypionate, Biolab Sanus Farmacêutica Ltda.) and twelve subjects received the reference product (Cyclofemina®, 25 mg/0.5 mL medroxyprogesterone acetate + 5 mg/0.5 mL estradiol cypionate, Millet Roux Ltda.). The formulations (test or reference) were administered in a single intramuscular dose (1 ampoule) after an overnight fast (approximately 8 h). Blood samples (9 mL) were collected via a venous catheter into heparinized tubes at times pre-dose (0 h) and 6, 12, 24, 48, 72, 96, 120, 168, 240, 288, 336, 432, 504, 672, 840, 1008, 1176, 1344, 1512, 1680, 1848, and 2016 h after drug administration to measure medroxyprogesterone; and pre-dose (-48, -24 and 0 h) e 2, 4, 6, 8, 10, 12, 24, 48, 72, 96, 120, 168, 240, 288, 336, 432, 504, 672, 840, and 1008 h after drug administration to measure estradiol cypionate. The safety assessment was based on recording adverse events throughout the study duration. The subjects systolic and diastolic pressures, heart rate and temperature were determined prior and at approximately 4, 8 and 12 h after drug administration. The clinical evaluation and the laboratory tests were also performed at the end of the study.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
24
Administration of a single intramuscular dose of an injectable formulation containing medroxyprogesterone acetate 25 mg/mL + estradiol cypionate 5 mg/mL after an overnight fast.
Administration of a single intramuscular dose of an injectable formulation containing medroxyprogesterone acetate 25 mg/ampole + estradiol cypionate 5 mg/ampole after an overnight fast.
Galeno Desenvolvimento de Pesquisas Clinicas Ltda. - ME
Campinas, São Paulo, Brazil
Measurement of medroxyprogesterone acetate and estradiol cypionate plasma levels
Blood sampling for the determination of plasma levels of medroxyprogesterone acetate and estradiol cypionate in participants of each treatment group.
Time frame: 0-1008 hours after drug administration
Measurement of estradiol cypionate plasma levels
Blood sampling for the determination of plasma levels of estradiol cypionate in participants of each treatment group.
Time frame: -48 to 1008 hours after drug administration
Maximum Plasma Concentration (Cmax) of medroxyprogesterone acetate
Determination of maximum plasma concentration of medroxyprogesterone acetate on plasma concentrations of samples obtained.
Time frame: 0 - 1008 hours after drug administration
Maximum Plasma Concentration (Cmax) of estradiol cypionate
Determination of maximum plasma concentration of estradiol cypionate on plasma concentrations of samples obtained.
Time frame: 0 - 1008 hours after drug administration
Area Under the Curve (AUC) of medroxyprogesterone acetate
Determination of area Under the Curve of medroxyprogesterone acetate from plasma concentrations versus time curve of samples obtained.
Time frame: 0 - 1008 hours after drug administration
Area Under the Curve (AUC) of estradiol cypionate
Determination of area Under the Curve of estradiol cypionate from plasma concentrations versus time curves of samples obtained.
Time frame: 0 - 1008 hours after drug administration
Number of adverse events per participant
Number of adverse events, in each treatment group, including clinically relevant alterations of vital signs and laboratory tests results.
Time frame: Up to 1008 hours after drug administration
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