NCT04819906

Effect of Estetrol Monohydrate (E4) on QTc Interval

A Randomized, Placebo- and Active-controlled 4-way Crossover Study in Healthy Subjects to Evaluate the Effect of E4 on the QTc Interval

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 32 (actual)
• Sponsor: Estetra · Industry
• Sex: Female
• Age: 40 Years – 65 Years
• Healthy volunteers: Accepted

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.

Conditions

• Prolonged QTc Interval

Interventions

Type	Name	Description
DRUG	Estetrol 20 mg	One estetrol monohydrate (E4) 20 mg tablet plus four matching placebo tablets orally once
DRUG	Estetrol 100 mg	Five estetrol monohydrate (E4) 20 mg tablets orally once
DRUG	Placebo	Five placebo tablets orally once
DRUG	Moxifloxacin 400 mg	One moxifloxacin 400 mg tablet orally once (open-label)

Timeline

• Start date: 2021-03-09
• Primary completion: 2021-07-14
• Completion: 2021-07-14
• First posted: 2021-03-29
• Last updated: 2023-09-15

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study