Clinical trial NCT04209543: Estetrol for the Treatment of Moderate to Severe Vasomotor Symptoms in Postmenopausal Women (E4Comfort Study I)
Official title: 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 I)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Vasomotor Symptoms
Menopausal Symptoms
Keywords: Estetrol
Hot Flushes
Vasomotor Symptoms
Lead sponsor: Estetra
Sponsor class: INDUSTRY
Collaborators: name: ICON Clinical Research
First posted: 2019-12-24
Enrollment: 1570
Sex: FEMALE
Minimum age (years): 40
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This study consists of 3 blinded arms (efficacy part) and 1 open-label arm (safety part).
Primary purpose: TREATMENT

Brief 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)

Detailed description: This study consists of two-parts, performed with 2 separate groups of participants:

• 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 E4 15 mg or 20 mg or placebo for up to 13 consecutive weeks. For endometrial protection, all non-hysterectomized participants were treated with 200 mg progesterone (P4) once daily for 14 consecutive days, after completion of the E4/placebo treatment. This part of the study consisted of 3 treatment groups.

• Safety Study Part: The Endometrial and General Safety Study Part is designed to evaluate the general safety, endometrial safety, secondary efficacy (lipid, glucose metabolism, health-related quality of life (HRQoL) and treatment satisfaction) of E4 in non-hysterectomized participants. All participants received E4 20 mg in combination with 100 mg P4 continuously for up to 53 weeks.

Eligibility criteria: 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 randomization;
* For hysterectomized subjects: documented hysterectomy must have occurred at least 6 weeks prior to the start of screening. Hysterectomy can be total or subtotal (i.e., cervix was not removed);
* For non-hysterectomized subjects: uterus with bi-layer endometrial thickness ≤ 4 mm on TVUS;
* For non-hysterectomized subjects: an evaluable endometrial biopsy taken during screening that reveals no abnormal results, i.e., presence of hyperplasia (simple or complex, with or without atypia), presence of carcinoma, and presence of disordered proliferative endometrium findings. The screening biopsy should have sufficient endometrial tissue for diagnosis;
* Seeking treatment for relief of VMS associated with menopause;

  1. For the Efficacy Study part: at least 7 moderate to severe bothersome VMS per day or at least 50 moderate to severe bothersome VMS per week in the last 7 consecutive days during the Screening period;
  2. For the Endometrial and General Safety Study part: at least 1 moderate to severe VMS per week;
* Body mass index ≥ 18.0 kg/m\^2 to ≤ 38.0 kg/m\^2;
* A mammogram that shows no sign of significant disease performed during screening or within 9 months prior to the start of screening ;
* Post-menopausal status defined as any of the following:
* For non-hysterectomized subjects:

  1. at least 12 months of spontaneous amenorrhea with serum follicle stimulating hormone (FSH) \>40 milli-International unit (mIU)/mL (value obtained after washout of estrogen/progestin containing drugs, see exclusion criteria 18 and 20);
  2. or at least 6 months of spontaneous amenorrhea with serum FSH \>40 mIU/mL and E2 \<20 pg/mL (\<73.4 pmol/L,value obtained after washout of estrogen/progestin containing drugs, see exclusion criteria 18 and 20);
  3. or at least 6 weeks postsurgical bilateral oophorectomy;
* For hysterectomized subjects:

  1. serum FSH \>40 mIU/mL and E2 \<20 pg/mL (\<73.4 pmol/L, values obtained after washout of estrogen/progestin containing drug see exclusion criteria 18 and 20);
  2. or at least 6 weeks post-surgical bilateral oophorectomy.
* Good physical and mental health, in the judgement of the Investigator as based on medical history, physical and gynecological examination and clinical assessments performed prior Visit 1;
* Able to understand and comply with the protocol requirements, instructions, and protocol-stated restrictions;
* Able and willing to complete trial daily paper diaries (if applicable) and questionnaires.

Exclusion Criteria:

* History of malignancy with the exception of basal cell or squamous cell carcinoma of the skin if diagnosed more than 1 year prior to the Screening visit;
* Any clinically significant findings found by the Investigator at the breast examination and/or on mammography suspicious of breast malignancy that would require additional clinical testing to rule out breast cancer (however, simple cysts confirmed by ultrasound are allowed);
* Papanicolaou (PAP) test with atypical squamous cells undetermined significance (ASC-US) or higher (low-grade intraepithelial lesion \[LSIL\], atypical squamous cells- cannot exclude high-grade intraepithelial lesion \[HSIL\] \[ASC-H\], HSIL, dysplastic or malignant cells) in sub-totally hysterectomized and non-hysterectomized subjects . Note: ASC-US is allowed if a reflex human papilloma virus (HPV) testing is performed and is negative for high risk oncogene HPV subtypes 16 and 18;
* For non-hysterectomized subjects:

  1. History or presence of uterine cancer, endometrial hyperplasia, or disordered proliferative endometrium;
  2. Presence of endometrial polyps;
  3. Undiagnosed vaginal bleeding or undiagnosed abnormal uterine bleeding;
  4. Endometrial ablation;
  5. Any uterine/endometrial abnormality that in the judgment of the investigator contraindicates the use of estrogen and/or progestin therapy. This includes presence or history of adenomyosis or significant myoma;
* Systolic blood pressure (BP) higher than 130 mmHg, diastolic BP higher than 80 mmHg during screening;
* History of venous or arterial thromboembolic disease (e.g., superficial or deep vein thrombosis, pulmonary embolism, stroke, myocardial infarction, angina pectoris, etc.), or first degree family history of venous thromboembolism (VTE);
* History of known acquired or congenital coagulopathy or abnormal coagulation factors, including known thrombophilia's;
* Laboratory values of fasting glucose above 125 mg/dL (\>6.94 mmol/L) and/or glycated hemoglobin above 7%18;
* Dyslipoproteinemia (LDL \>190 mg/dL \[\>4.91 mmol/L\] and/or triglycerides \>300 mg/dL \[\>3.39 mmol/L\])19;
* Subjects smoking \>15 cigarettes per day;
* Presence or history of gallbladder disease, unless cholecystectomy has been performed;
* Systemic lupus erythematosus;
* Any malabsorption disorders including gastric by-pass surgery;
* History of acute liver disease in the preceding 12 months before the start of screening or presence or history of chronic or severe liver disease \[alanine transaminase (ALT) or aspartate transaminase (AST) \>2x upper limit of normal (ULN), bilirubin \>1.5 ULN\]; or liver tumors;
* Chronic or current acute renal impairment (estimated glomerular filtration rate \<60 ml/min);
* Porphyria;
* Diagnosis or treatment of major psychiatric disorder (e.g., schizophrenia, bipolar disorder, etc.), in the judgement of the Investigator;
* Use of estrogen/progestin containing drug(s) up to:

  1. 1 week before screening start for vaginal non systemic hormonal products (rings, creams, gels);
  2. 4 weeks before screening start for vaginal or transdermal estrogen or estrogen/progestin products;
  3. 8 weeks before screening start for oral estrogen and/or progestin products and/or selective estrogen receptor modulator therapy;
  4. 8 weeks before screening start for intrauterine progestin therapy;
  5. 3 months before screening start for progestin implants or estrogen alone injectable drug therapy;
  6. 6 months before screening start for estrogen pellet therapy or progestin injectable drug therapy;
* Use of androgen/dehydroepiandrosterone (DHEA) containing drugs:

  1. 8 weeks before screening start for oral, topical, vaginal or transdermal androgen;
  2. 6 months before screening start for implantable or injectable androgen therapy;
* Use of phytoestrogens or black cohosh for the treatment of VMS up to 2 weeks before the start of screening;
* For the women participating in the Efficacy Study part: use of prescription or over-the-counter products used for the treatment of VMS, e.g., anti-depressants: paroxetine, escitalopram, methyldopa, opioid and clonidine up to 4 weeks before the start of screening, and venlafaxine and desvenlafaxine up to 3 months before the start of screening , and not willing to stop these during their participation in the trial;
* Not willing to stop any hormonal products as described in exclusion criteria 18, 19 and 20, during their participation in the trial;
* Inadequately treated hyperthyroidism with abnormal TSH and free T4 at screening. Subjects with low or high TSH are allowed if free T4 at screening is within normal range;
* History or presence of allergy/intolerance to the investigational product or drugs of this class or any component of it, or history of drug or other allergy that, in the opinion of the Investigator contraindicates subject participation;
* History of alcohol or substance abuse (including marijuana, even if legally allowed) or dependence in the previous 12 months before the start of screening as determined by the Investigator, based on reported observations;
* Sponsor or contract research organization (CRO) employees or employees under the direct supervision of the Investigator and/or involved directly in the trial;
* Subjects with known or suspected history of a clinically significant systemic disease, unstable medical disorders, life-threatening disease or current malignancies that would pose a risk to the subject in the opinion of the Investigator;
* Participation in another investigational drug clinical trial within 1 month (30 days) or having received an investigational drug within the last month (30 days) before the start of screening;
* Is judged by the Investigator to be unsuitable for any reason;
* For non-hysterectomized subjects to be included in the USA and Canada: history or presence of allergy to peanuts.

Primary outcomes:
measure: Mean change in weekly frequency of moderate to severe vasomotor symptoms (VMS) from Baseline to Week 4 (Efficacy Study Part)
timeFrame: Baseline and Week 4
measure: Mean change in weekly frequency of moderate to severe vasomotor symptoms (VMS) from Baseline to Week 12 (Efficacy Study Part)
timeFrame: Baseline and Week 12
measure: Mean change in severity of moderate to severe vasomotor symptoms (VMS) from Baseline to Week 4 (Efficacy Study Part)
timeFrame: Baseline and Week 4
measure: Mean change in severity of moderate to severe vasomotor symptoms (VMS) from Baseline to Week 12 (Efficacy Study Part)
timeFrame: Baseline and Week 12
measure: Incidence of endometrial hyperplasia with up to 12 months of treatment based on endometrial biopsies (Endometrial and General Safety Study Part)
timeFrame: Screening and Week 53
Secondary outcomes:
measure: Mean change from Baseline to Week 1 in the weekly frequency and severity of moderate to severe vasomotor symptoms (VMS) (Efficacy Study Part)
timeFrame: Baseline and Week 1
measure: Mean change from Baseline to Week 2 in the weekly frequency and severity of moderate to severe vasomotor symptoms (VMS) (Efficacy Study Part)
timeFrame: Baseline and Week 2
measure: Mean change from Baseline to Week 3 in the weekly frequency and severity of moderate to severe vasomotor symptoms (VMS) ((Efficacy Study Part)
timeFrame: Baseline and Week 3
measure: Mean change from Baseline to Week 4 in the weekly frequency and severity of moderate to severe vasomotor symptoms (VMS) (Efficacy part)
timeFrame: Baseline and Week 4
measure: Mean change from Baseline to Week 5 in the weekly frequency and severity of moderate to severe vasomotor symptoms (VMS) (Efficacy Study Part)
timeFrame: Baseline and Week 5
measure: Mean change from Baseline to Week 6 in the weekly frequency and severity of moderate to severe vasomotor symptoms (VMS) (Efficacy Study Part)
timeFrame: Baseline and Week 6
measure: Mean change from Baseline to Week 7 in the weekly frequency and severity of moderate to severe vasomotor symptoms (VMS) (Efficacy Study Part)
timeFrame: Baseline and Week 7
measure: Mean change from Baseline to Week 8 in the weekly frequency and severity of moderate to severe vasomotor symptoms (VMS) (Efficacy Study Part)
timeFrame: Baseline and Week 8
measure: Mean change from Baseline to Week 9 in the weekly frequency and severity of moderate to severe vasomotor symptoms (VMS) (Efficacy Study Part)
timeFrame: Baseline and Week 9
measure: Mean change from Baseline to Week 10 in the weekly frequency and severity of moderate to severe vasomotor symptoms (VMS) (Efficacy Study Part)
timeFrame: Baseline and Week 10
measure: Mean change from Baseline to Week 11 in the weekly frequency and severity of moderate to severe vasomotor symptoms (VMS) (Efficacy Study Part)
timeFrame: Baseline and Week 11
measure: Mean change from Baseline to Week 12 in the weekly frequency and severity of moderate to severe vasomotor symptoms (VMS) (Efficacy Study Part)
timeFrame: Baseline and Week 12
measure: Mean change from Baseline to Week 1 in the weekly frequency and severity of mild, moderate and severe vasomotor symptoms (VMS) (Efficacy Study Part)
timeFrame: Baseline and Week 1
measure: Mean change from Baseline to Week 2 in the weekly frequency and severity of mild, moderate and severe vasomotor symptoms (VMS) (Efficacy Study Part)
timeFrame: Baseline and Week 2
measure: Mean change from Baseline to Week 3 in the weekly frequency and severity of mild, moderate and severe vasomotor symptoms (VMS) (Efficacy Study Part)
timeFrame: Baseline and Week 3
measure: Mean change from Baseline to Week 4 in the weekly frequency and severity of mild, moderate and severe vasomotor symptoms (VMS) (Efficacy Study Part)
timeFrame: Baseline and Week 4
measure: Mean change from Baseline to Week 5 in the weekly frequency and severity of mild, moderate and severe vasomotor symptoms (VMS) (Efficacy Study Part)
timeFrame: Baseline and Week 5
measure: Mean change from Baseline to Week 6 in the weekly frequency and severity of mild, moderate and severe vasomotor symptoms (VMS) (Efficacy Study Part)
timeFrame: Baseline and Week 6
measure: Mean change from Baseline to Week 7 in the weekly frequency and severity of mild, moderate and severe vasomotor symptoms (VMS) (Efficacy Study Part)
timeFrame: Baseline and Week 7
measure: Mean change from Baseline to Week 8 in the weekly frequency and severity of mild, moderate and severe vasomotor symptoms (VMS) (Efficacy Study Part)
timeFrame: Baseline and Week 8
measure: Mean change from Baseline to Week 9 in the weekly frequency and severity of mild, moderate and severe vasomotor symptoms (VMS) (Efficacy Study Part)
timeFrame: Baseline and Week 9
measure: Mean change from Baseline to Week 10 in the weekly frequency and severity of mild, moderate and severe vasomotor symptoms (VMS) (Efficacy Study Part)
timeFrame: Baseline and Week 10
measure: Mean change from Baseline to Week 11 in the weekly frequency and severity of mild, moderate and severe vasomotor symptoms (VMS) (Efficacy Study Part)
timeFrame: Baseline and Week 11
measure: Mean change from Baseline to Week 12 in the weekly frequency and severity of mild, moderate and severe vasomotor symptoms (VMS) (Efficacy Study Part)
timeFrame: Baseline and Week 12
measure: Percentage of participants with 50% reduction from Baseline in the weekly frequency of moderate to severe vasomotor symptoms (VMS) at Week 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 (Efficacy Study Part)
timeFrame: Baseline, Week 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12
measure: Percentage of participants with 50% reduction from Baseline in the weekly frequency of mild, moderate, and severe vasomotor symptoms (VMS) at Week 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 (Efficacy Study Part)
timeFrame: Baseline, Week 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12
measure: Percentage of participants with 75% reduction from Baseline in the weekly frequency of moderate to severe VMS at Week 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 (Efficacy Study Part)
timeFrame: Baseline, Week 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12
measure: Percentage of participants with 75% reduction from Baseline in the weekly frequency of mild, moderate, and severe VMS at Week 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 (Efficacy Study Part)
timeFrame: Baseline, Week 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12
measure: Percentage of participants with a clinically important difference (CID) compared to Baseline in the weekly frequency of moderate to severe VMS at Week 4 using the Clinical Global Impression (CGI) questionnaire (Efficacy Study Part)
timeFrame: Week 4
measure: Percentage of participants with a clinically important difference (CID) compared to baseline in the weekly frequency of moderate to severe VMS at Week 12 using the Clinical Global Impression (CGI) questionnaire (Efficacy Study Part)
timeFrame: Week 12
measure: Change from Baseline to Week 12 in vulvovaginal atrophy (VVA) symptoms (Efficacy Study Part)
timeFrame: Baseline and Week 12
measure: Change from Baseline to Week 12 in the vulvovaginal atrophy (VVA) symptom that is initially identified by the participant as being the most bothersome using the VVA questionnaire at baseline (Efficacy Study Part)
timeFrame: Baseline and Week 12
measure: Change from Baseline to Week 12 in plasma concentration of triglycerides (Efficacy Study Part)
timeFrame: Baseline and Week 12
measure: Change from Baseline to Week 12 in plasma concentration of low-density lipoprotein (LDL)-cholesterol (Efficacy Study Part)
timeFrame: Baseline and Week 12
measure: Change from Baseline to Week 12 in plasma concentration of total cholesterol (Efficacy Study Part)
timeFrame: Baseline and Week 12
measure: Change from Baseline to Week 12 in the total cholesterol/high density cholesterol (HDL) cholesterol ratio (Efficacy Study Part)
timeFrame: Baseline and Week 12
measure: Change from Baseline to Week 12 in the HDL-cholesterol ratio (Efficacy Study Part)
timeFrame: Baseline and Week 12
measure: Change from Baseline to Week 12 in plasma concentration of lipoprotein (a) (Efficacy Study Part)
timeFrame: Baseline and Week 12
measure: Change from Baseline to Week 12 in fasting glycaemia (Efficacy Study part)
timeFrame: Baseline and Week 12
measure: Change from Baseline to Week 12 in plasma concentration of insulin (Efficacy Study Part)
timeFrame: Baseline and Week 12
measure: Change from Baseline to Week 12 in plasma concentration of glycated hemoglobin (Efficacy Study Part)
timeFrame: Baseline and Week 12
measure: Change from Baseline to Week 12 in Homeostasis model-assessment-estimated insulin resistance (HOMA-IR) (Efficacy Study Part)
timeFrame: Baseline and Week 12
measure: Change from baseline to Week 12 in health-related quality of life assessment (HRQoL) using the menopause-specific Quality of Life (MENQOL) questionnaire (Efficacy Study Part)
timeFrame: Baseline and Week 12
measure: Total score in treatment satisfaction using the Clinical Global Impression (CGI) questionnaire (Efficacy Study Part)
timeFrame: Weeks 4 and 12
measure: Number of participants with treatment-emergent adverse events (TEAEs) (Efficacy Study Part)
timeFrame: From baseline to Follow-up visit (up to Week 16)
measure: Number of participants with changes in physical and gynecological examination results (Efficacy Study Part)
timeFrame: Screening and Week 13
measure: Number of participants with changes in vital sign results (Efficacy Study Part)
timeFrame: From screening to Week 13
measure: Number of participants with changes in electrocardiogram (ECG) results (Efficacy Study Part)
timeFrame: Screening and Week 13
measure: Number of participants with changes in breast examination results (Efficacy Study Part)
timeFrame: Screening and Week 13
measure: Number of participants with changes in routine clinical laboratory test results (Efficacy Study Part)
timeFrame: Screening, Baseline and Week 13
measure: Change from baseline to each measured time point in endometrial thickness (Efficacy Study Part)
timeFrame: Screening, Week 13, Week 16
measure: Frequency of subjects in the different endometrial categories according to Blaustein's pathology (Efficacy Study Part)
timeFrame: Screening and Week 13
measure: Number of participants with vaginal bleeding and/or spotting during each 28-day cycle of treatment with E4 (Efficacy Study Part)
timeFrame: From Baseline up to Follow-up (Week 16)
measure: Number of days with bleeding and/or spotting during each 28-day cycle of treatment (Efficacy Study Part)
timeFrame: From Baseline up to Follow-up (Week 16)
measure: Number of participants with amenorrhea (absence of any bleeding or spotting) during each 28-day cycle of treatment with E4 (Efficacy Study Part)
timeFrame: From Baseline up to Follow-up (Week 16)
measure: Cumulative rates of amenorrhea (Efficacy Study Part)
timeFrame: From Baseline up to Follow-up (Week 16)
measure: Number of participants with treatment-emergent adverse events (TEAEs) (Endometrial and General Safety Part)
timeFrame: From baseline to Week 53
measure: Number of participants with changes in physical and gynecological examination results (Endometrial and General Safety Part)
timeFrame: Screening and Week 53
measure: Number of participants with changes in vital sign results (Endometrial and General Safety Part)
timeFrame: From screening to Week 53
measure: Number of participants with changes in breast examination results (Endometrial and General Safety Part)
timeFrame: From screening to Week 53
measure: Number of participants with changes in electrocardiogram (ECG) results (Endometrial and General Safety Part)
timeFrame: Screening and Week 53
measure: Number of participants with changes in mammography results (Endometrial and General Safety Part)
timeFrame: Screening and Week 53
measure: Number of participants with changes in routine clinical laboratory test results (Endometrial and General Safety Part)
timeFrame: Screening, Baseline and Week 13
measure: Number of women with vaginal bleeding and/or spotting during each 28-day cycle of treatment with E4 (Endometrial and General Safety Part)
timeFrame: From Baseline to Week 53
measure: Number of days with bleeding and/or spotting during each 28-day cycle of treatment (Endometrial and General Safety Part)
timeFrame: From Baseline to Week 53
measure: Number of participants with amenorrhea (absence of any bleeding or spotting) during each 28-day cycle of treatment with E4 (Endometrial and General Safety Part)
timeFrame: From Baseline to Week 53
measure: Cumulative rates of amenorrhea (Endometrial and General Safety Part)
timeFrame: From Baseline to Week 53
measure: Change from Baseline to Weeks 12 and 52 in health-related quality of life assessment (HRQoL) using the menopause-specific Quality of Life (MENQOL) questionnaire (Endometrial and General Safety Part)
timeFrame: Baseline and Weeks 12 and 52
measure: Total score in treatment satisfaction assessed after 4, 12 and 52 weeks of treatment using the Clinical Global Impression (CGI) questionnaire (Endometrial and General Safety Part)
timeFrame: Weeks 4, 12, and 52
measure: Change from Baseline to Weeks 12 and 52 in plasma concentration of triglycerides (Endometrial and General Safety Part)
timeFrame: Baseline and Weeks 12 and 52
measure: Change from Baseline to Weeks 12 and 52 in plasma concentration of high-density lipoprotein (HDL)-cholesterol (Endometrial and General Safety Part)
timeFrame: Baseline and Weeks 12 and 52
measure: Change from Baseline to Weeks 12 and 52 in plasma concentration of low-density lipoprotein (LDL)-cholesterol (Endometrial and General Safety Part)
timeFrame: Baseline and Weeks 12 and 52
measure: Change from Baseline to Weeks 12 and 52 in plasma concentration of total cholesterol (Endometrial and General Safety Part)
timeFrame: Baseline and Weeks 12 and 52
measure: Change from Baseline to Weeks 12 and 52 in the total cholesterol/high density cholesterol (HDL) cholesterol ratio (Endometrial and General Safety Part)
timeFrame: Baseline and Weeks 12 and 52
measure: Change from Baseline to Weeks 12 and 52 in plasma concentration of lipoprotein (a) (Endometrial and General Safety Part)
timeFrame: Baseline and Weeks 12 and 52
measure: Change from Baseline to Weeks 12 and 52 in fasting glycaemia (Endometrial and General Safety Part)
timeFrame: Baseline and Weeks 12 and 52
measure: Change from Baseline to Weeks 12 and 52 in plasma concentration of insulin (Endometrial and General Safety Part)
timeFrame: Baseline and Weeks 12 and 52
measure: Change from Baseline to Weeks 12 and 52 in plasma concentration of glycated hemoglobin (Endometrial and General Safety Part)
timeFrame: Baseline and Weeks 12 and 52
measure: Change from Baseline to Weeks 12 and 52 in Homeostasis model-assessment-estimated insulin resistance (HOMA-IR) (Endometrial and General Safety Part)
timeFrame: Baseline and Weeks 12 and 52
measure: Change from Baseline to each measured time point in endometrial thickness (Endometrial and General Safety Study Part)
timeFrame: Screening, Baseline, Weeks 13, 29, and 53
measure: Frequency of subjects in the different endometrial categories according to Blaustein's pathology (Endometrial and General Safety Study Part)
timeFrame: Screening and Week 53
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Estetra Study Site
state: Alabama
city: Mesa
country: United States
facility: Estetra Study Site
state: Arizona
city: Phoenix
country: United States
facility: Estetra Study Site
state: Arizona
city: Phoenix
country: United States
facility: Precision Trials AZ, LLC
state: Arizona
city: Tucson
country: United States
facility: Noble Clinical Research
state: Arizona
city: Canoga Park
country: United States
facility: Hope Clinical Research, LLC
state: California
city: Pomona
country: United States
facility: Estetra Study Site
state: California
city: Sacramento
country: United States
facility: Clinical Trials Research
state: California
city: Sacramento
country: United States
facility: Estetra Study Site
state: California
city: Thousand Oaks
country: United States
facility: Estetra Study Site
state: California
city: West Covina
country: United States
facility: Estetra Study Site
state: California
city: Denver
country: United States
facility: Velocity Clinical Research
state: Colorado
city: Altamonte Springs
country: United States
facility: Estetra Study Site
state: Florida
city: Coconut Creek
country: United States
facility: Estetra Study Site
state: Florida
city: Hialeah
country: United States
facility: Estetra Study Site
state: Florida
city: Jacksonville
country: United States
facility: Clinical Neuroscience Solutions, Inc.
state: Florida
city: Lake Worth
country: United States
facility: Altus Research
state: Florida
city: Miami Lakes
country: United States
facility: San Marcus Research Clinic, Inc.
state: Florida
city: Miami
country: United States
facility: Medical Research Center of Miami II
state: Florida
city: Miami
country: United States
facility: Miami Clinical Research
state: Florida
city: Miami
country: United States
facility: Genoma Research Group, Inc.
state: Florida
city: Miami
country: United States
facility: Estetra Study Site
state: Florida
city: New Port Richey
country: United States
facility: Estetra Study Site
state: Florida
city: North Miami
country: United States
facility: Estetra Study Site
state: Florida
city: Ocoee
country: United States
facility: Estetra Study Site
state: Florida
city: Orlando
country: United States
facility: Clinical Neurosciecne Solutions, Inc. dba CNS Healthcare
state: Florida
city: Ormond Beach
country: United States
facility: Estetra Study Site
state: Florida
city: Palm Harbor
country: United States
facility: Estetra Study Site
state: Florida
city: Pembroke Pines
country: United States
facility: Estetra Study Site
state: Florida
city: Pinellas Park
country: United States
facility: Estetra Study Site
state: Florida
city: Port Saint Lucie
country: United States
facility: Estetra Study Site
state: Florida
city: Sarasota
country: United States
facility: Physician Care Clinical Research, LLC
state: Florida
city: Tampa
country: United States
facility: Estetra Study Site
state: Florida
city: Atlanta
country: United States
facility: Estetra Study Site
state: Georgia
city: Morrow
country: United States
facility: Infinite Clinical Trials
state: Georgia
city: Savannah
country: United States
facility: Fellows Research Alliance, Inc.
state: Georgia
city: Idaho Falls
country: United States
facility: Clinical Research Prime
state: Idaho
city: Marrero
country: United States
facility: Praetorian Pharmaceutical Research
state: Louisiana
city: Norfolk
country: United States
facility: Meridian Clinical Research
state: Nebraska
city: Las Vegas
country: United States
facility: Jubilee Clinical Research, Inc
state: Nevada
city: Las Vegas
country: United States
facility: Excel Clinical Research
state: Nevada
city: Berlin
country: United States
facility: Hassman Research Institute
state: New Jersey
city: Albuquerque
country: United States
facility: Bosque Women's Care
state: New Mexico
city: Charlotte
country: United States
facility: PMG Research of Charlotte, LLC
state: North Carolina
city: Durham
country: United States
facility: Estetra Study Site
state: North Carolina
city: Columbus
country: United States
facility: Estetra Study Site
state: Ohio
city: Englewood
country: United States
facility: Estetra Study Site
state: Ohio
city: Philadelphia
country: United States
facility: Estetra Study Site
state: Pennsylvania
city: Myrtle Beach
country: United States
facility: Magnolia Ob/Gyn Research Center
state: South Carolina
city: Chattanooga
country: United States
facility: Estetra Study Site
state: Tennessee
city: Dallas
country: United States
facility: Cedar Health Research, LLC
state: Texas
city: Fort Worth
country: United States
facility: Signature Gyn Services
state: Texas
city: Houston
country: United States
facility: Estetra Study Site
state: Texas
city: Houston
country: United States
facility: Biopharma Informatic, Inc. Research Center
state: Texas
city: Houston
country: United States
facility: Estetra Study Site
state: Texas
city: Irving
country: United States
facility: Cedar Health Research LLC
state: Texas
city: Plano
country: United States
facility: Estetra Study Site
state: Texas
city: San Antonio
country: United States
facility: Estetra Study Site
state: Texas
city: San Antonio
country: United States
facility: Estetra Study Site
state: Texas
city: San Antonio
country: United States
facility: Estetra Study Site
state: Texas
city: Pleasant Grove
country: United States
facility: Estetra Study Site
state: Utah
city: Norfolk
country: United States
facility: Estetra Study Site
state: Virginia
city: Virginia Beach
country: United States
facility: Tidewater Clinical Research Inc
state: Virginia
city: Bellevue
country: United States
facility: Northwest Clinical Research Center
state: Washington
city: Morgantown
country: United States
facility: IMA Clinical Research
state: West Virginia
city: Buenos Aires
country: Argentina
facility: IDIM - Instituto de Investigaciones Metabolicas
city: Caba
country: Argentina
facility: Centro Medico Dra Laura Maffei Investigacion Clinica Aplicada
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: Mautalen Salud e Investigacion
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: Fundacion Respirar (Centro Medico Dra. De Salvo) - Instituto Argentino de Investigaciones Clinicas (IAIC) S.R.L
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: Glenny Corp. S. A. / Bioclinica Argentina
city: Lanús
country: Argentina
facility: Centro de Investigacion Medico Lanus-CIMEL
city: Mar Del Plata
country: Argentina
facility: Centro De Investigaciones Medicas Mar Del Plata
city: Mar Del Plata
country: Argentina
facility: Instituto de Investigaciones Clinicas Mar del Plata
city: Rosario
country: Argentina
facility: Instituto Medico de la Fundacion Estudios Clinicos
city: Belo Horizonte
country: Brazil
facility: Centro De Medicina Reprodutiva Ltda - Clinica Origen
city: Botucatu
country: Brazil
facility: Faculdade de Medicina de Botucatu - UNESP
city: Brasília
country: Brazil
facility: Centro De Pesquisa Clinica Do Brasil
city: Campinas
country: Brazil
facility: IPCC-Instituto de Pesquisa Clinica de Campinas
city: Campinas
country: Brazil
facility: University of Campinas Medical School
city: Chapeco
country: Brazil
facility: Centro de Oncologia de Santa Catarina Ltda / Supera Oncologia
city: Cuiabá
country: Brazil
facility: Instituto Tropical de Medicina Reprodutiva - Clinica INTRO
city: Curitiba
country: Brazil
facility: CEPEME / CERHFAC Centro De Estudos E Pesquisas Em Reproducao Humana E Fertilizacao Assistida De Curitiba Ltda
city: Fortaleza
country: Brazil
facility: Federal University Of Ceara
city: Natal
country: Brazil
facility: Universidade Federal Do Rio Grande Do Norte/ Maternidade Escola Januario Cicco
city: Passo Fundo
country: Brazil
facility: Hospital Sao Vicente de Paulo, Associacao Hospitalar Beneficente Sao Vicente de Paulo
city: Porto Alegre
country: Brazil
facility: Hospital de Clinicas de Porto Alegre (HCPA)
city: Porto Alegre
country: Brazil
facility: Nucleo de Pesquisa Clinica do Rio Grande do Sul Ltda
city: Porto Alegre
country: Brazil
facility: Unidade de Pesquisa Clínica - Centro de Medicina Reprodutiva
city: Porto Alegre
country: Brazil
facility: Hospital Sao Lucas da PUC
city: Rio De Janeiro
country: Brazil
facility: lnstituto Brasil De Pesquisa Clinica S.A (IBPCLIN)
city: Sao Paulo
country: Brazil
facility: CPQuali Pesquisa Clinica LTDA
city: São Bernardo Do Campo
country: Brazil
facility: CEMEC - Faculdade de Medicina do ABC
city: São Paulo
country: Brazil
facility: CPClin- Centro de Pesquisas Clinicas Ltda./Clinica Dr. Freddy Goldberg Eliaschewitz
city: São Paulo
country: Brazil
facility: Hospital Perola Byington/ Centro de Referencia da Saude da Mulher
city: São Paulo
country: Brazil
facility: Universidade Federal De Sao Paulo (Unifesp) - Hospital Sao Paulo (Hsp)
city: São Paulo
country: Brazil
facility: CEPIC - Centro Paulista de Investigacao Clinica e Servicos Medicos Ltda
city: São Paulo
country: Brazil
facility: College - Centro De Pesquisa Clinica E Servicos Medicos Ltda College - Centro De Pesquisa Clinica (Baby Center Medicina Reprodutiva)
city: Vitória
country: Brazil
facility: CEDOES - Centro de Diagnostico e Pesquisa da Osteoporose do Espirito Santo
city: Votuporanga
country: Brazil
facility: Santa Casa De Votuporanga-Philanthropic hospital
city: Brampton
country: Canada
facility: Aggarwal and Associates Limited
city: Quebec City
country: Canada
facility: DIEX Research Quebec
city: Quebec City
country: Canada
facility: Alpha Recherche Clinique
city: Quebec
country: Canada
facility: Clinique Rsf Inc.
city: Québec
country: Canada
facility: Estetra Study Site
city: Québec
country: Canada
facility: Alpha Recherche Clinique
city: Québec
country: Canada
facility: Estetra Study Site
city: Sarnia
country: Canada
facility: Estetra Study Site
city: Sherbrooke
country: Canada
facility: Diex Research Sherbrooke Inc.
city: Victoriaville
country: Canada
facility: Diex Recherche
city: Waterloo
country: Canada
facility: Fadia El Boreky Medicine Professional Corporation
city: Brno
country: Czechia
facility: Dr. Vladimir Dvorak MD, Office Of
city: Brno
country: Czechia
facility: Gynekologie Meda Brno
city: Ceske Budejovice
country: Czechia
facility: Dr. Jiri Tiser MD, Office of
city: Cheb
country: Czechia
facility: Gynekologie Cheb s.r.o.
city: Hradec Králové
country: Czechia
facility: MUDr. Martin Stepan s.r.o.
city: Jihlava
country: Czechia
facility: Gynekologie Jihlava
city: Nachod
country: Czechia
facility: MUDr. Jan Kestranek - gynekologicka ambulance
city: Olomouc
country: Czechia
facility: Estetra Study Site
city: Olomouc
country: Czechia
facility: G-CENTRUM Olomouc, s.r.o.
city: Olomouc
country: Czechia
facility: NEUMED gynekologicka ambulance s.r.o.
city: Ostrava
country: Czechia
facility: Dr. Karel Buchta MD, Office of
city: Plzen
country: Czechia
facility: Dr. Martina Maresova Rosenbergova MD, Office of
city: Plzen
country: Czechia
facility: Gynekologicka ambulance Gyncare MUDr. Michael Svec s.r.o.
city: Praha 5
country: Czechia
facility: Mediva s.r.o
city: Praha 8
country: Czechia
facility: Gynekologicko-porodnicka klinika
city: Praha 9
country: Czechia
facility: Dr. Lubomir Mikulasek, MD office Of
city: Rychnov nad Kneznou
country: Czechia
facility: Vestra Clinics
city: Tábor
country: Czechia
facility: Dr. Tereza Smrhova-Kovacs MD, Office of
city: Vysoke
country: Czechia
facility: Dr. Ivana Salamonova MD, Office of
city: České Budějovice
country: Czechia
facility: MUDr. Petr Sak
city: České Budějovice
country: Czechia
facility: GYN-Mika s.r.o.
city: Debrecen
country: Hungary
facility: Szent Anna Privat Surgery-Szent Anna Maganrendelo
city: Pécs
country: Hungary
facility: Pecsi Tudomanyegyetem (PTE) Altalanos Orvostudomanyi Kar (AOK) - Klinikai Kozpont Szuleszeti es Nogyogyaszati Klinika
city: Szeged
country: Hungary
facility: Univ. of Szeged Faculty of General Medicine Albert Szent-Gyaergyi
city: Szentes
country: Hungary
facility: Csongrad Megyei Dr. Bugyi Istvan Korhaz
city: Bologna
country: Italy
facility: Ginecologia e Fisiopatologia della Riproduzione Umana,UO Ostetricia e Ginecologia,Policlinico S.Orsola-Malpighi
city: Calabria
country: Italy
facility: Ospedale Pugliese
city: Firenze
country: Italy
facility: Universita degli Studi di Firenze - Azienda Ospedaliero Universitaria Careggi, DAI Materno Infantile, SOD Ginecologia e Ostetricia
city: Modena
country: Italy
facility: Azienda Ospedaliero - Universitaria Policlinico di Modena
city: Perugia
country: Italy
facility: Universita degli Studi di Perugia - Policlinico Monteluce - Centro di Medicina Perinatale e della Riproduzione
city: Pisa
country: Italy
facility: Azienda Ospedaliero Universitaria Pisana
city: Roma
country: Italy
facility: Universita degli Studi di Roma La Sapienza - Umberto I Policlinico di Roma
city: Roma
country: Italy
facility: Policlinico Univ. Agostino Gemelli
city: Kaunas
country: Lithuania
facility: Saules Family Medicine Centre
city: Kaunas
country: Lithuania
facility: UAB VAKK - Dr. Kildos Klinika
city: Klaipėda
country: Lithuania
facility: Klaipedos Miesto Poliklinika
city: Vilnius
country: Lithuania
facility: Public Institution Centro Poliklinika
city: Vilnius
country: Lithuania
facility: UAB Seimos gydytojas
city: Vilnius
country: Lithuania
facility: JSC Maxmeda
city: Vilnius
country: Lithuania
facility: JSC Kardiolita
city: Vilnius
country: Lithuania
facility: Vilnius University Hospital Santaros klinikos
city: Białystok
country: Poland
facility: Prywatna Klinika Polozniczo - Ginekologiczna Sp. Z O.O.
city: Białystok
country: Poland
facility: Centrum Ginekologii Endokrynologii i Medycyny Rozrodu Artemida
city: Bydgoszcz
country: Poland
facility: Osrodek Badan Klinicznych IN-VIVO
city: Bydgoszcz
country: Poland
facility: Przychodnia Srodmiescie Sp. z o.o.
city: Elbląg
country: Poland
facility: Mital Site Badania Kliniczne
city: Gdańsk
country: Poland
facility: Copernicus Podmiot Leczniczy - Szpital sw. Wojciecha
city: Katowice
country: Poland
facility: Centrum Medyczne Mikolowska Dr Adam Sipinski
city: Katowice
country: Poland
facility: Clinical Medical Research sp. z o.o.
city: Katowice
country: Poland
facility: NZOZ Sanas
city: Katowice
country: Poland
facility: Centrum Medyczne Angelius Provita
city: Katowice
country: Poland
facility: Pro Familia Altera Sp. z o.o.
city: Katowice
country: Poland
facility: NZOZ Vita Longa Sp. z o.o.
city: Katowice
country: Poland
facility: Gyncentrum Sp. z o.o.
city: Kraków
country: Poland
facility: Pratia MCM Krakow
city: Kraków
country: Poland
facility: Grazyna Bogutyn Medico Praktyka Lekarska
city: Lodz
country: Poland
facility: NZOZ Medican
city: Lublin
country: Poland
facility: Centrum Medyczne Chodzki
city: Lublin
country: Poland
facility: KO-MED Centra Kliniczne Sp. z o.o., Osrodek Badan Klinicznych w Lublinie II
city: Lublin
country: Poland
facility: Niepubliczny Zak¿ad Opieki Zdrowotnej PROFI-MED
city: Olsztyn
country: Poland
facility: ETYKA Osrodek Badan Klinicznych
city: Piaseczno
country: Poland
facility: Centrum Innowacyjnych Terapii Sp. z o.o.
city: Piotrków Trybunalski
country: Poland
facility: IRMED Osrodek Badan Klinicznych
city: Poznań
country: Poland
facility: Clinical Research Center Spolka z ograniczona odpowiedzialnoscia Medic-R Spolka Komandytowa
city: Skorzewo
country: Poland
facility: Estetra Study Site
city: Szczecin
country: Poland
facility: Twoja Przychodnia - Szczecinskie Centrum Medyczne
city: Warsaw
country: Poland
facility: Nzoz Zieniewicz Medical
city: Warszawa
country: Poland
facility: Centrum Badawcze Wspolczesnej Terapii Prywatny Gabinet Lekarski Dr Anna Bochenek-Mularczyk
city: Warszawa
country: Poland
facility: ETG Warszawa
city: Warszawa
country: Poland
facility: Medical Concierge Centrum Medyczne
city: Wroclaw
country: Poland
facility: Marek Elias Gabinety Ginekologiczne
city: Zamość
country: Poland
facility: ETG Zamosc
city: Łódź
country: Poland
facility: Salve Medica-Przychodnia
city: Braşov
country: Romania
facility: Centrul Medical Unirea Policlinica Brasov
city: Braşov
country: Romania
facility: Centrul Medical de Diagnostic si Tratament Ambulatoriu Neomed SRL
city: Bucharest
country: Romania
facility: Spitalul Clinic Nicolae Malaxa
city: Bucuresti
country: Romania
facility: SC Centrul Medical Unirea SRL
city: Bucuresti
country: Romania
facility: SC Quantum Medical Center SRL
city: Bucuresti
country: Romania
facility: Centrul Medical Euromed
city: Bucuresti
country: Romania
facility: Sana Monitoring
city: Bucuresti
country: Romania
facility: Centrul Medical Unirea - Spitalul Baneasa
city: Caracal
country: Romania
facility: Spitalul Municipal Caracal
city: Constanta
country: Romania
facility: Centrul Medical Unirea
city: Craiova
country: Romania
facility: Vitaplus Medclin SRL
city: Târgu-Mureş
country: Romania
facility: Spitalul De Urgenta Targu Mures-Emergency University County Hospital
city: Târgu-Mureş
country: Romania
facility: SC Centrul Medical Unirea SRL
city: Irkutsk
country: Russian Federation
facility: Scientific Center for Family Health Problems and Human Reproduction
city: Krasnoyarsk
country: Russian Federation
facility: Krasnoyarsk State Medical University named after Prof. V.F. VoinoYasenetsky
city: Moscow
country: Russian Federation
facility: LLC Olla-Med
city: Moscow
country: Russian Federation
facility: Scientific Centre Of Obsterics, Gynecology And Perinatology n.a.academican V.I.Kulakov of Federal Agency of High Tech Medical Care
city: Novosibirsk
country: Russian Federation
facility: JCS Avicenna
city: Rostov-on-Don
country: Russian Federation
facility: Clinical diagnostic center Zdorovye
city: Saint Petersburg
country: Russian Federation
facility: Saint-Petersburg State Healthcare Institution Maternity hospital
city: Saint Petersburg
country: Russian Federation
facility: The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott - Center Menopause and Women's Health
city: Saint Petersburg
country: Russian Federation
facility: Astarta Clinic
city: Saint Petersburg
country: Russian Federation
facility: Woman's consulting center #22
city: Samara
country: Russian Federation
facility: Closed Joint Stock Company Medical Company Idk
city: Dubnica nad Váhom
country: Slovakia
facility: MCM GYNPED, s.r.o.
city: Poprad
country: Slovakia
facility: BrenCare, s. r. o.
city: Gavà
country: Spain
facility: Diatros S.L.P
city: Madrid
country: Spain
facility: Instituto Palacios, Salud y Medicina de la Mujer
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio, Hospital de la Mujer
city: Corby
country: United Kingdom
facility: Accellacare - (MeDiNova Limited) - Northamptonshire
city: Coventry
country: United Kingdom
facility: Accellacare (Previously MeDiNova) Warwickshire Quality Research Site
city: Glasgow
country: United Kingdom
facility: CPS Research
city: High Wycombe
country: United Kingdom
facility: Egin Research Ltd
city: London
country: United Kingdom
facility: Queen Charlotte's and Chelsea Hospital - Imperial College Healthcare NHS Trust
city: Northwood
country: United Kingdom
facility: Accellacare - (MeDiNova Limited) - North London
city: Orpington
country: United Kingdom
facility: Accellacare - South London
city: Orpington
country: United Kingdom
facility: Estetra Study Site
city: Romford
country: United Kingdom
facility: Accellacare - (MeDiNova Limited) - East London
city: Shipley
country: United Kingdom
facility: Accellacare - (MeDiNova Limited) - Yorkshire
city: Wokingham
country: United Kingdom
facility: Accellacare - (MeDiNova Limited) - West London
Study officials:
References: