Effect of Estetrol Monohydrate (E4) on QTc Interval
Condition: Prolonged QTc Interval
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of this study is:

        -  to evaluate if E4 has any effect on how the heart beats when a single dose is given at
           two different dose levels;

        -  to determine the ability to detect small changes in how the heart beats using a positive
           control: moxifloxacin, a quinolone antibiotic approved by the FDA as a positive control
           in thorough QT (TQT) studies;

        -  to assess the safety and tolerability of a single dose of E4 administered at two
           different dose levels;

        -  to measure the amount of study drug in the blood stream and how long it takes for the
           body to eliminate it (Pharmacokinetics) after administration.
    

Detailed description: 
      This is a Phase 1, multicenter, randomized, placebo- and active-controlled, partially
      double-blinded, single-dose, 4-way crossover study in healthy postmenopausal female
      participants to evaluate the effect of E4 on the QTc interval. All participants will receive
      all 4 study treatments (E4 therapeutic dose [20 mg]; E4 supratherapeutic dose [100 mg];
      placebo; moxifloxacin [400 mg]) in a randomized sequence.

      E4 and placebo administration will be blinded while moxifloxacin will be provided in an
      open-label fashion.

      Participants will report to the clinical research unit (CRU) for the eligibility screening
      within 28 days prior to the first study drug administration. Participants will sign the study
      specific informed consent form (ICF) prior to any study specific screening procedures being
      performed.

      In each study period, the participants will be confined in the CRU from the day before dosing
      (Day -1) until all safety assessments have been completed on Day 2, for a total of 2 days per
      period. Each study period will be separated by a 14 day (±2 days) washout.

      Cardiodynamic assessment using continuous 12-lead ECG (Holters) recordings will be performed
      on Day 1 of each treatment period starting approximately 1 hour before dosing and ending
      approximately 25 hours after dosing. ECGs will be extracted serially pre- and postdose and at
      predefined time points. Blood draws for PK will be performed in all periods after each ECG
      extraction.

      All participants (including participants who terminate the study prematurely) will receive a
      follow-up call 7 (±2) days after the last administration of study treatment to determine if
      any adverse events (AEs) have occurred since the last study visit.
    

Intervention name(s): Estetrol 20 mg; Estetrol 100 mg; Placebo; Moxifloxacin 400 mg
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): One estetrol monohydrate (E4) 20 mg tablet plus four matching placebo tablets orally once; Five estetrol monohydrate (E4) 20 mg tablets orally once; Five placebo tablets orally once; One moxifloxacin 400 mg tablet orally once (open-label)
Other intervention name(s): E4 20 mg; E4 100 mg
Intervention MeSH terms: Moxifloxacin
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Estetrol; Moxifloxacin