Effect of Food on the Bioavailability of 15 mg Estetrol/3 mg Drospirenone Tablets in Healthy Female Volunteers

Study Overview
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Brief Summary
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This single-center, open-label, randomized, balanced, single-dose, two-treatment, two-period, two-sequence crossover study was conducted under medical supervision in 28 healthy female volunteers.

Detailed Description
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Food effect bioavailability studies are usually conducted for new drugs and drug products to assess the effect of food on the rate and extent of absorption of a drug when the drug product is administered shortly after a meal (fed conditions), as compared to administration under fasting conditions. Therefore, this study was designed to characterize the effect of a high fat meal on the bioavailability of E4 and DRSP after administration of a single tablet containing 15 mg E4 and 3 mg DRSP. All subjects entered the study site at least 12 hours before each dosing and fasted for at least 10 hours prior to each dose. All subjects were to receive both Treatment A (Reference; a single 15 mg E4/3 mg DRSP tablet without food (fasted)) and Treatment B (Test; a single 15 mg E4/3 mg DRSP tablet with food (fed)) either at the first treatment period (Period 1) or the second treatment period (Period 2). Approximately half of the subjects were randomized to receive either Treatment A followed by Treatment B (Sequence AB), or Treatment B followed by Treatment A (Sequence BA).

Official Title
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A Study to Characterize the Effect of Food on the Bioavailability of 15 mg Estetrol (E4)/3 mg Drospirenone (DRSP) Tablets in Healthy Female Volunteers

Conditions
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Contraception

Intervention / Treatment
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* Drug: 15 mg E4/3 mg DRSP


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Overtly healthy females. Between the ages of 18 and 45 years, inclusive. Non-smokers who have not used tobacco or nicotine in any form during the 3 months prior to the screening visit. Between the body mass index (BMI) of 18 and 30 kg/m2, inclusive, and body weight 45kg. Negative serum pregnancy test results at screening and negative urine pregnancy test results before dosing. Willing to use double-barrier methods of non-hormonal contraception during the entire study period. Exclusion Criteria: Potential study subjects were not entered into and/or may have been discontinued from the study if any of the following applied: Use of progestogen-only contraceptive methods [e.g., minipill, implant or, intrauterine system (IUS)] during the last 3 months prior to the first dose or, depot progestogen preparations or an injectable hormonal method of contraception (e.g., Depo-Provera) during the last 6 months prior to the first dose. Use (within 28 days prior to first dose) of other hormonal contraceptive method. Use of any prescription drugs (except thyroid hormone supplements) or herbal supplements acting on CYP3A4 functions (e.g., St. John's Wort), within 28 days prior to the first dose until study completion, any over-the-counter (OTC) medication (including paracetamol) or dietary supplements (vitamins included) within 14 days prior to the first study dose until study completion.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: 15 mg E4/3 mg DRSP without food<br>Treatment A (Reference): a single 15 mg E4/3 mg DRSP tablet without food (fasted). | Drug: 15 mg E4/3 mg DRSP<br>* All subjects received both Treatment A and Treatment B either at the first treatment period (Period 1) or the second treatment period (Period 2). Approximately half of the subjects was randomized to receive either Treatment A followed by Treatment B (Sequence AB), or Treatment B followed by Treatment A (Sequence BA)<br>* Other names: 15 mg Estetrol/3 mg Drospirenone;|
| Other: 15 mg E4l/3 mg DRSP with food<br>Treatment B (Test): a single 15 mg E4/3 mg DRSP tablet with food (fed) | Drug: 15 mg E4/3 mg DRSP<br>* All subjects received both Treatment A and Treatment B either at the first treatment period (Period 1) or the second treatment period (Period 2). Approximately half of the subjects was randomized to receive either Treatment A followed by Treatment B (Sequence AB), or Treatment B followed by Treatment A (Sequence BA)<br>* Other names: 15 mg Estetrol/3 mg Drospirenone;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum concentration (Cmax) of estetrol in plasma | PK sampling | From day 1 to 4 during both period 1 and period 2 | 
| Cmax of drospirenone in plasma | PK sampling | From day 1 to 4 during both period 1 and period 2 | 
| Area under the plasma concentration versus time curve from time 0 to the last determined concentration (AUC0-tdlc) of estetrol |  | From day 1 to 4 during both period 1 and period 2 | 
| AUC0-tdlc of drospirenone |  | From day 1 to 4 during both period 1 and period 2 | 
| AUC0-inf of estetrol | PK sampling | Day 1 to 4 during both period 1 and period 2 | 
| AUC0-inf of drospirenone | PK sampling | Day 1 to 4 during both period 1 and period 2 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects with adverse events as a measure of safety and tolerability |  | From up to day 28 before randomization (28 day screening/run-in period) to day 4 of the Period 2 |