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

NCT04209543 ↗

Phase 3 Completed 1570 enrolled Estetra ICON Clinical Research · collab

RandomizedParallel-groupQuadruple-blindTreatment

Summary

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

Timeline

Start: 2019-12-30
Primary completion: 2024-02-08
Completion: 2024-02-08

Publications

Simoncini T, Bouchard C, Cloes M, Taziaux M, Palacios S, de Medeiros SF, Vrabii V, Archer DF, Panay N. Estetrol (E4) for the treatment of moderate to severe vasomotor symptoms in postmenopausal women - Efficacy and safety results from the phase 3 E4COMFORT I multicenter, placebo-controlled study. Maturitas. 2026 Jun;209:108965. doi: 10.1016/j.maturitas.2026.108965. Epub 2026 Apr 28.
Panay N, Simoncini T, Taziaux M, Bouchard C, Black A, Kapoor E, Utian W, Foidart JM, Lobo RA. Estetrol for the treatment of moderate to severe vasomotor symptoms in postmenopausal women: The design of the E4COMFORT I and II trials. Maturitas. 2026 Jan;204:108781. doi: 10.1016/j.maturitas.2025.108781. Epub 2025 Nov 17.
Gaspard U, Taziaux M, Jost M, Coelingh Bennink HJT, Utian WH, Lobo RA, Foidart JM. A multicenter, randomized, placebo-controlled study to select the minimum effective dose of estetrol in postmenopausal participants (E4Relief): part 2-vaginal cytology, genitourinary syndrome of menopause, and health-related quality of life. Menopause. 2023 May 1;30(5):480-489. doi: 10.1097/GME.0000000000002167. Epub 2023 Feb 20.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	ESTETROL ANHYDROUS	Other / unclassified	15 mg	Oral
Subject	ESTETROL ANHYDROUS	Other / unclassified	20 mg	Oral
Background	Progesterone	Other / unclassified	100 mg	Oral
Background	Progesterone	Other / unclassified	200 mg	Oral

Indications

No indication recorded.