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

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

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.

Study Overview

• Status: Completed
• Conditions: Contraception
• Intervention / Treatment: Drug: 15 mg E4/3 mg DRSP

Detailed Description

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).

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: 15 mg E4/3 mg DRSP without food; Treatment A (Reference): a single 15 mg E4/3 mg DRSP tablet without food (fasted).	Drug: 15 mg E4/3 mg DRSP; 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); Other Names: 15 mg Estetrol/3 mg Drospirenone
Other: 15 mg E4l/3 mg DRSP with food; Treatment B (Test): a single 15 mg E4/3 mg DRSP tablet with food (fed)	Drug: 15 mg E4/3 mg DRSP; 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); Other Names: 15 mg Estetrol/3 mg Drospirenone

What is the study measuring?

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	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

Collaborators and Investigators

• Sponsor: Estetra
• Investigators: Principal Investigator: Dobrin Sviranov, MD, Comac Medical

Study record dates

Study Major Dates

• Study Start: August 1, 2015
• Primary Completion (Actual): October 1, 2015
• Study Completion (Actual): April 1, 2016

Study Registration Dates

• First Submitted: April 15, 2016
• First Submitted That Met QC Criteria: July 28, 2016
• First Posted (Estimate): August 2, 2016

Study Record Updates

• Last Update Posted (Estimate): August 2, 2016
• Last Update Submitted That Met QC Criteria: July 28, 2016
• Last Verified: June 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Natriuretic Agents; Diuretics; Hormone Antagonists; Mineralocorticoid Receptor Antagonists; Diuretics, Potassium Sparing; Drospirenone
• Other Study ID Numbers: Es0001-C101; 2015-001764-19 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No