NCT02874248

E4/DRSP Single and Multiple Dose PK and Early QT Study

A Randomized, Double-blind, Placebo-controlled, Parallel, Single Center Study to Investigate the Pharmacokinetics, Safety, Tolerability, and QT Concentration-effect Modelling of Estetrol in Combination With Drospirenone After Single and Multiple Dosing in Healthy Women

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 55 (actual)
• Sponsor: Estetra · Industry
• Sex: Female
• Age: 18 Years – 50 Years
• Healthy volunteers: Accepted

Summary

This study is conducted to evaluate the effect of single and multiple therapeutic and supratherapeutic oral doses of E4/DRSP combinations on PK parameters, safety, tolerability and on cardiac repolarization, as detected by QT interval corrected with Fridericia's formula (QTcF).

Detailed description

This will be a randomized, double-blind, placebo-controlled, parallel, single center study in healthy female subjects. A total of 42 female subjects will be enrolled in 3 groups of 14 subjects each. A potential fourth group of 14 healthy female subjects may be added. In each group, subjects will be randomized in a 2.5 to 1 ratio between active (n=10) and placebo (n=4). Subjects will receive a single dose on Day 1 and, after a washout of at least 14 days, multiple doses on 14 consecutive days from Days 15 to 28. Group 1 and Group 2 may be dosed in parallel. After completion of Group 1 and Group 2, a Dose Escalation Report (DER), including PK data up to at least 24 hours post-last dose, will be prepared by the Principal Investigator (PI). Escalation to the planned dose level of 60 mg E4/12 mg DRSP will only proceed if the safety and tolerability of the dose levels of 15 mg E4/3 mg DRSP and 30 mg E4/6 mg DRSP up to 24 hours post-last dose, are acceptable to the PI and the Sponsor and, if deemed necessary by the Independent Ethics Committee (IEC) following their review of the protocol, after a statement of no objection of the DER from the IEC. After completion of Group 3, a second DER, including PK data, will be prepared by the PI. If in Group 3 the expected exposure level of approximately 4 times the exposure of Group 1 is not achieved, and treatment in Group 3 is well tolerated, an additional group with 14 subjects may be enrolled, using a dose level that is estimated to result in at least 4 times the exposure after administration of the 15 mg E4/3 mg DRSP therapeutic dose.

Conditions

• Contraception

Interventions

Type	Name	Description
DRUG	15 mg E4/3 mg DRSP	a single oral dose of 15 mg E4/3 mg DRSP (n=10) followed, after a washout of at least 14 days, by multiple oral doses of 15 mg E4/3 mg DRSP (n=10) once daily for 14 days
DRUG	30 mg E4/6 mg DRSP	a single oral dose of 30 mg E4/6 mg DRSP, followed, after a washout of at least 14 days, by multiple oral doses of 30 mg E4/6 mg DRSP once daily for 14 days
DRUG	60 mg E4/12 mg DRSP	a single oral dose of 60 mg E4/12 mg DRSP, followed, after a washout of at least 14 days, by oral doses of 60 mg E4/12 mg DRSP once daily for 14 days
DRUG	Visually matching placebo	a single oral dose of a placebo which visually matches the active medication, followed, after a washout of at least 14 days, by multiple oral doses of matching placebo once daily for 14 days
DRUG	75 mg E4/15 mg DRSP	a single oral dose of 75 mg E4/15 mg DRSP, followed, after a washout of at least 14 days, by oral doses of 75 mg E4/15 mg DRSP once daily for 14 days

Timeline

• Start date: 2016-05-01
• Primary completion: 2016-11-21
• Completion: 2016-11-21
• First posted: 2016-08-22
• Last updated: 2017-04-21