Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Estetrol · 2 trials · 2 indications
The weekly frequency of moderate to severe VMS at Baseline and Week 4 is defined as the total number (sum) of all recorded moderate to severe VMS experienced during the last 7 consecutive days prior randomization for Baseline and at Week 4. Mean change = mean weekly frequency at Week 4 - mean weekly frequency at Baseline
The weekly frequency of moderate to severe VMS at Baseline and Week 12 is defined as the total number (sum) of all recorded moderate to severe VMS experienced during the last 7 consecutive days prior randomization for Baseline and at Week 12. Mean change = mean weekly frequency at Week 12 - mean weekly frequency at Baseline
The severity score is derived as follows: mild = 1, moderate = 2, and severe = 3. The mean severity score of VMS at Baseline and Week 4 is defined as the arithmetic mean of the daily severity score values of moderate and severe VMS observed from the last 7 days prior randomization for Baseline and of moderate and severe VMS observed at Week 4. Baseline and Week 4 severity score = \[(2 x number of moderate VMS) + (3 x number of severe VMS)\]/ (total number of moderate + severe VMS). Mean change = mean severity score at Week 4 - mean severity score at Baseline
The severity score is derived as follows: mild = 1, moderate = 2, and severe = 3. The mean severity score of VMS at Baseline and Week 12 is defined as the arithmetic mean of the daily severity score values of moderate and severe VMS observed from the last 7 days prior randomization for Baseline and of moderate and severe VMS observed at Week 12. Baseline and Week 12 severity score = \[(2 x number of moderate VMS) + (3 x number of severe VMS)\]/ (total number of moderate + severe VMS). Mean change = mean severity score at Week 12 - mean severity score at Baseline
Endometrial biopsies will be centrally evaluated by three independent expert pathologists from different institutions, blinded to treatment group and to each other's readings. The concurrence of two of the three pathologists will be accepted as the final diagnosis. If there is no agreement among the three pathologists, the most severe pathologic diagnosis, i.e., atypical hyperplasia \>complex hyperplasia \>simple hyperplasia \>benign endometrium, will be used as the final diagnosis.
Weekly frequency of moderate to severe VMS at Baseline = total number (sum) of all recorded moderate to severe VMS experienced during the last 7 consecutive days prior randomization (Week 0). Weekly frequency of moderate to severe VMS at Week X = total number (sum) of all recorded moderate to severe VMS experienced during the week X.
Mean severity score of VMS at Baseline: arithmetic mean of daily severity score values of moderate and severe VMS during the last 7 days prior randomization (Week 0). Mean severity score of VMS at Week 4 or 12: arithmetic mean of daily severity score values of moderate and severe VMS during Week 4 or 12. Daily severity score of VMS at Baseline = \[(2 x number of moderate VMS) + (3 x number of severe VMS)\]/(total number of moderate + severe VMS)\], if at least one moderate to severe VMS was recorded during the day. If documented absence of moderate to severe VMS during the day, daily severity was set to zero. Daily severity score of VMS Post-Baseline = \[(1 x number of mild VMS) + (2 x number of moderate VMS) + (3 x number of severe VMS)\]/(total number of mild + moderate + severe VMS)\], if at least one mild to severe VMS was recorded during the day. If documented absence of VMS during the day, daily severity was set to zero. Severity score: mild=1, moderate=2, severe=3.
| Arm | Type | Description |
|---|---|---|
| Estetrol 15 mg - Efficacy Part | EXPERIMENTAL | Estetrol (E4) 15 mg was administered orally once daily for a minimum of 12 weeks and not longer than 13 weeks. |
| Estetrol 20 mg - Efficacy Part | EXPERIMENTAL | Estetrol (E4) 20 mg was administered orally once daily for a minimum of 12 weeks and not longer than 13 weeks. |
| Placebo - Efficacy Part | PLACEBO_COMPARATOR | Placebo was administered orally once daily for a minimum of 12 weeks and not longer than 13 weeks. |
| Estetrol 20 mg + P4 100 mg - Safety Part | EXPERIMENTAL | Estetrol (E4) 20 mg and Progesterone (P4) 100 mg was administered once daily for up to 53 weeks. |
| Estetrol 15 mg - Efficacy Study Part | EXPERIMENTAL | Estetrol (E4) 15 mg, administered orally once daily for up to 53 weeks. |
| Estetrol 20 mg - Efficacy Study Part | EXPERIMENTAL | Estetrol (E4) 20 mg, administered orally once daily for up to 53 weeks. |
| Placebo - Efficacy Study Part | PLACEBO_COMPARATOR | Placebo, administered orally once daily for up to 53 weeks. |
| Estetrol 20 mg - Safety Study Part | EXPERIMENTAL | Estetrol (E4) 20 mg, administered orally once daily for up to 53 weeks. |
| Name | Type | Description |
|---|---|---|
| Estetrol | DRUG | Estetrol oral tablet: administered orally once daily |
| Placebo | DRUG | Placebo oral tablet: administered orally once daily |
| Progesterone | DRUG | Progesterone oral tablet: administered orally once daily |
| Estetrol oral tablet | DRUG | Estetrol oral tablet, administered orally once daily. |
| Placebo oral tablet | DRUG | Placebo oral tablet, administered orally once daily. |
Inclusion Criteria: * Signed and dated written informed consent form and any required privacy authorization prior to the initiation of any trial procedure, after the nature of the trial has been explained according to local regulatory requirements; * Females, ≥ 40 up to ≤ 65 years of age at randomi...
Estetrol is an investigational small molecule being developed for the treatment of moderate to severe vasomotor symptoms, commonly known as hot flashes, in postmenopausal women. It is being studied as a potential therapy for menopausal symptoms and is currently in Phase 3 clinical development.
Estetrol is a small molecule that acts as an estrogen receptor agonist. It is being studied for its ability to modulate estrogen receptors to alleviate vasomotor symptoms associated with menopause. The exact molecular target is the estrogen receptor, which plays a key role in regulating menopausal symptoms.
Estetrol is being developed by Icon Plc, a biopharmaceutical company traded on the NASDAQ under the ticker symbol ICLR. The company is conducting clinical trials to evaluate the safety and efficacy of Estetrol for the treatment of vasomotor symptoms in postmenopausal women.
Estetrol is currently in Phase 3 clinical development. Two Phase 3 trials have been completed, both of which were randomized, double-blind, and placebo-controlled. The drug is investigational and has not yet been approved by regulatory authorities for any indication.
Estetrol has been studied in two completed Phase 3 clinical trials: NCT04090957, known as E4Comfort II, which enrolled 1015 participants, and NCT04209543, known as E4Comfort Study I, which enrolled 1570 participants. Both trials evaluated the drug in postmenopausal women with moderate to severe vasomotor symptoms.
Estetrol is sometimes referred to as E4, as indicated by the trial names E4Comfort I and E4Comfort II. The drug is a small molecule being investigated for the treatment of vasomotor symptoms in postmenopausal women, and these alternative names are used in clinical trial documentation.