Comparative Bioavailability of Two Injectable Suspension Formulations of Medroxyprogesterone Acetate+Estradiol Cypionate

NCT ID: NCT03443089

Last Updated: 2018-02-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-03-31
• Study Completion Date: 2017-08-01

Brief Summary

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.

Detailed Description

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.

Conditions

Contraception

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Test formulation

Single intramuscular dose administration (1 ampoule) of medroxyprogesterone acetate 25 mg/mL+ estradiol cypionate 5 mg/mL (Depomês®, Biolab Sanus Farmacêutica Ltda.)

Group Type: EXPERIMENTAL

Test formulation

Intervention Type: DRUG

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.

Reference formulation

Single intramuscular dose administration (1 ampoule) of medroxyprogesterone acetate 25 mg/ampole + estradiol cypionate 5 mg/ampole (Cyclofemina®, Millet Roux Ltda.)

Group Type: ACTIVE_COMPARATOR

Reference formulation

Intervention Type: DRUG

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.

Interventions

Test formulation

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.

Intervention Type: DRUG

Reference formulation

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.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Body-mass index (BMI) ≥19.0 kg/m² and ≤ 27.5 kg/m²
• With regular cycles, without use of hormonal contraceptives (pills at least 3 months and injectables at least 1 year) and not using hormone replacement therapy
• Not pregnant or breastfeeding
• Good state of health
• Non-smoker or ex-smoker for at least 6 month
• Written informed consent, after having been informed about benefits and potential risks of the clinical trial, as well as details of the insurance taken out to cover the subjects participating in the clinical trial

Exclusion Criteria

• Existing cardiac, hepatic and/or haematological diseases or pathological findings, which might interfere with the safety or tolerability and/or pharmacokinetics and/or pharmacodynamics of the active ingredient
• History of relevant central nervous system (CNS) and/or psychiatric disorders and/or currently treated CNS and/or psychiatric disorders
• Known allergic reactions to the active ingredients used or to constituents of the pharmaceutical preparations
• Subjects with severe allergies or multiple drug allergies, unless it is judged as not relevant for the clinical trial by the investigator
• Positive anti-HIV-test (if positive to be verified by western blot), HBs-AGtest (if positive to be verified by test for HBc-IgM) or anti-HCV-test
• Admitted for any reason up to 8 weeks before the start of the first treatment period of this study
• History of or current drug or alcohol dependence
• Subjects who are on a diet which could affect the pharmacokinetics of the active ingredient
• Regular intake of caffeine containing food or beverages of ≥ 500 mg caffeine per day
• Blood donation or other blood loss of more than 400 ml within the last 3 months prior to individual enrolment of the subject
• Participation in a clinical trial during the last 6 months prior to individual enrolment of the subject
• Positive pregnancy test, delivery or abortion in the 12 weeks prior to the planned hospitalization date.
• Subjects who are unable to understand the written and verbal instructions, in particular regarding the risks and inconveniences they will be exposed to during their participation in the clinical trial

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

Biolab Sanus Farmaceutica

INDUSTRY

Sponsor Role: collaborator

Galeno Desenvolvimento de Pesquisas Clínicas

OTHER_GOV

Sponsor Role: lead

Responsible Party

Gilberto De Nucci

Doctor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Gilberto De Nucci, Doctor

Role: PRINCIPAL_INVESTIGATOR

Galeno Desenvolvimento de Pesquisas Clinicas Ltda

Locations

Galeno Desenvolvimento de Pesquisas Clinicas Ltda. - ME

Campinas, São Paulo, Brazil

Countries

Brazil

Other Identifiers

GDN 022/16

Identifier Type: -

Identifier Source: org_study_id