E4/DRSP Single and Multiple Dose PK and Early QT Study
Condition: Contraception
Study type: Interventional
Phase: Phase 1

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.
    

Intervention name(s): 15 mg E4/3 mg DRSP; 30 mg E4/6 mg DRSP; 60 mg E4/12 mg DRSP; Visually matching placebo; 75 mg E4/15 mg DRSP
Intervention type(s): Drug; Drug; Drug; Drug; Drug
Intervention description(s): 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; 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; 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; 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; 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
Other intervention name(s): 15 mg estetrol and 3 mg drospirenone; 30 mg estetrol and 6 mg drospirenone; 60 mg estetrol and 12 mg drospirenone
Intervention MeSH terms: Drospirenone
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Other