E4Relief (Response to Estetrol in Life Improvement for MEnopausal-associated Hot Flushes)

NCT02834312 | Completed Phase 2

• 2 other identifiers: MIT-Do0001-C2012015-004018-44
• Study Type: interventional
• Target: 260
• Locations: 1 country
• Sites: 1

Brief Summary

This dose-finding study is being conducted to select the daily oral dose of estetrol (E4) for the treatment of vasomotor symptoms (VMS) in post-menopausal women.

Conditions

Hot Flushes

Keywords

Estetrol; Vasomotor symptoms; Menopause

Outcome Measures

Primary Outcomes (4)

• Change in weekly frequency of moderate to severe VMS from baseline to week 4.

  From baseline to week 4

• Change in weekly frequency of moderate to severe VMS from baseline to week 12.

  From baseline to week 12

• Change in severity of moderate to severe VMS from baseline to week 4.

  The Severity Scoring System of VMS will be documented by the subjects by using the following scores: None (0) = No VMS symptoms; Mild (1) = Sensation of heat without sweating; Moderate (2) = Sensation of heat with sweating. Able to continue activity; Severe (3) = Sensation of heat with sweating. Causes cessation of activity.

  From baseline to week 4

• Change in severity of moderate to severe VMS from baseline to week 12.

  The Severity Scoring System of VMS will be documented by the subjects by using the following scores: None (0) = No VMS symptoms; Mild (1) = Sensation of heat without sweating; Moderate (2) = Sensation of heat with sweating. Able to continue activity; Severe (3) = Sensation of heat with sweating. Causes cessation of activity.

  From baseline to week 12

Secondary Outcomes (29)

• Change from baseline to week 12 in genitourinary symptoms (GSM) of menopause

  From baseline to week 12

• Change in the Menopause Rating Scale (MRS) from baseline to week 5.

  From baseline to week 5

• Change in the Menopause Rating Scale (MRS) from baseline to week 12.

  From baseline to week 12

• Change from baseline to week 12 in Vaginal pH.

  From baseline to week 12

• Change from baseline to week 12 in Vaginal Maturation Index (MI) (parabasal and superficial cells)

  From baseline to week 12

Study Arms (5)

2.5 mg estetrol

EXPERIMENTAL

Drug: Estetrol

5 mg estetrol

EXPERIMENTAL

Drug: Estetrol

10 mg estetrol

EXPERIMENTAL

Drug: Estetrol

15 mg estetrol

EXPERIMENTAL

Drug: Estetrol

placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Estetrol DRUG

All treatments (E4 \[2.5 mg, 5 mg, 10 mg, 15 mg\] capsule) will be administered once daily (QD) per os for at least 12 consecutive weeks until the last biological assessments (Day 90 maximum) have been performed.

Also known as: E4

10 mg estetrol; 15 mg estetrol; 2.5 mg estetrol; 5 mg estetrol

Placebo DRUG

1 capsule will be administered QD per os for at least 12 consecutive weeks until the last biological assessments (Day 90 maximum) have been performed.

placebo

Eligibility Criteria

• Age: 40 Years - 65 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Women presenting at least 7 moderate to severe hot flushes/day or at least 50 moderate to severe hot flushes/week in the week preceding randomization.
• Body Mass Index (BMI) between 18.0 and 35.0 kg/m², inclusive.
• Post-menopausal status.
• Intact uterus.
• Negative pregnancy test.
• Good physical and mental health.
• Subject has provided signed and dated written informed consent before admission to the study.
• Subject is able to understand and comply with the protocol requirements, instructions, and protocol-stated restrictions.

You may not qualify if:

• Uterine disease or any medical conditions associated with an increase in endometrial thickness.
• Any history of malignancy with the exception of basal cell (excluded if within the prior 2 years) or squamous cell (excluded if within the prior one year) carcinoma of the skin. Any clinically significant findings at the breast examination and/or on mammography suspicious of breast malignancy that would require additional clinical testing to rule out breast cancer.
• Abnormal cervical Pap smear.
• Systolic blood pressure (BP) outside the range 90 to 140 mmHg, diastolic BP outside the range 60 to 90 mmHg, and/or heart rate outside the range 40 to 100 bpm.
• Any clinically significant abnormality identified on the screening 12-lead ECG.
• History of venous or arterial thromboembolic disease, history of known coagulopathy or abnormal coagulation factors.
• Diabetes mellitus with poor glycaemic control.
• Dyslipoproteinaemia at screening.
• Smoking \>10 cigarettes/day.
• Presence or history of gallbladder disease, unless cholecystectomy has been performed.
• Systemic lupus erythematosus.
• Multiple sclerosis.
• Acute or chronic liver disease.
• Acute or chronic renal impairment.
• Uncontrolled thyroid disorders.

Sponsors & Collaborators

• Donesta Bioscience: lead
• SynteractHCR: collaborator

Study Sites (1)

Donesta Bioscience BV

Liège, 4000, Belgium

Location

Related Publications (1)

• 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.

  PMID: 36809193 DERIVED

Related Links

• Trial results were released to public view on the EudraCT (EudraCT Number: 2015-004018-44).

MeSH Terms

Conditions

Hot Flashes

Interventions

Estetrol

Condition Hierarchy (Ancestors)

Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Estriol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Donesta Bioscience

  Donesta Bioscience BV

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 7, 2016
• First Posted: July 15, 2016
• Study Start: May 1, 2016
• Primary Completion: January 22, 2018
• Study Completion: January 22, 2018
• Last Updated: November 18, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1)