NCT04090957

Estetrol for the Treatment of Moderate to Severe Vasomotor Symptoms in Postmenopausal Women (E4Comfort II)

A Randomized Double-blind Placebo Controlled Phase 3 Trial to Evaluate the Efficacy and Safety of Estetrol for the Treatment of Moderate to Severe Vasomotor Symptoms in Postmenopausal Women (E4Comfort Study II)

• Status: Completed
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 1,015 (actual)
• Sponsor: Estetra · Industry
• Sex: Female
• Age: 40 Years – 65 Years
• Healthy volunteers: Accepted

Summary

A two-part study designed to evaluate the effect of Estetrol (E4) 15 mg, 20 mg, or placebo on the severity and frequency of vasomotor symptoms (VMS) in the Efficacy Study Part and the safety of E4 20 mg in the Safety Study Part.

Detailed description

This is a two-part study: Arm 1, 2, and 3: randomized, double blind \- Efficacy Study Part: designed to evaluate the frequency and severity of vasomotor symptoms \[VMS\] in both hysterectomized and non hysterectomized postmenopausal participants after treatment with two doses of E4 (15 mg or 20 mg) or placebo for 12 consecutive weeks. Thereafter, treatment proceeded for a total duration of up to 53 weeks, to continue the evaluation of secondary efficacy (effect on hemostasis, lipid and glucose metabolism, bone turnover, health-related quality of life \[HRQoL\] and treatment satisfaction \[TS\]), safety and the effect on the endometrium. For endometrial protection, all non-hysterectomized subjects received 200 mg progesterone (P4) once daily for 14 consecutive days, after completion of the E4/placebo treatment. Arm 4: open label \- Safety Study Part: designed to evaluate the general safety, secondary efficacy (lipid and glucose metabolism, HRQoL and TS) after treatment with E4 20 mg for up to 53 weeks in hysterectomized and non hysterectomized postmenopausal participants. For endometrial protection, all non-hysterectomized subjects received 200 mg progesterone (P4) once daily for 14 consecutive days, after completion of the E4 treatment.

Conditions

• Vasomotor Symptoms
• Menopausal Symptoms

Interventions

Type	Name	Description
DRUG	Estetrol oral tablet	Estetrol oral tablet, administered orally once daily.
DRUG	Placebo oral tablet	Placebo oral tablet, administered orally once daily.

Timeline

• Start date: 2019-09-27
• Primary completion: 2022-08-18
• Completion: 2022-08-18
• First posted: 2019-09-16
• Last updated: 2025-12-26
• Results posted: 2025-12-26

Locations

117 sites across 2 countries: United States, Canada

Regulatory

• FDA-regulated drug study