Efficacy Study of Progesterone Tablet in Post-menopausal Women

Study Overview
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Brief Summary
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This is a phase II study intended to determine the effect of progesterone 5, 10 and 20 mg tablets compared to progesterone 100 mg capsules on the endometrial thickness of post-menopausal women under hormone therapy with estradiol.

Official Title
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Effect of Progesterone 5, 10, and 20 mg Tablets Compared To Progesterone 100 mg Capsules on the Endometrial Thickness of Post-Menopausal Women Under Hormone Therapy - A Prospective, Open-Label, Randomized, Four-Arm, Parallel-Group, Phase II Clinical Trial

Conditions
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Menopause

Intervention / Treatment
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* Drug: Progesterone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Availability for the entire study period Post-menopausal female defined as: at least 12 consecutive months of spontaneous amenorrhea and less than 10 years of spontaneous amenorrhea, and Follicle-stimulating hormone (FSH) levels > 40 milli International Units/ml Females with an intact uterus Moderate to severe climacteric vasomotor symptoms Aged of at least 40 years but not older than 65 years Body mass index (BMI) greater than or equal to 18.00 kg/m2 and below 30.00 kg/m2 Non- or ex-smoker; Endometrium thickness ≤4 mm on ultrasonography at screening Negative mammogram (dated < 2 years) Negative Pap smear test (dated < 1 year) Normal clinical breast examination Normal pelvic examination Have no clinically significant diseases captured in the medical history or evidence of clinically significant findings on physical examination, as determined by the medical investigator Willingness to adhere to the protocol requirements as evidenced by the informed consent form (ICF) duly read, signed and dated by the subject Exclusion Criteria: Use of any estrogen, progestin, or estrogen/progestin drug products, androgens, selective estrogen receptor modulators (SERMs), phytoestrogen supplements or natural products (soy, black cohosh, dong quai) during the past 3 months before the screening visit Use of any estrogen, progestin or androgen pellet or injectable therapy during the past 6 months before the screening visit Contraindications to hormone therapy: Active liver dysfunction or disease or history of severe liver disease Known, suspected or past history of hepatic tumors (benign or malign) Active or past history of arterial thromboembolic disease (e.g. angina, myocardial infarction, stroke, coronary heart disease, transient ischemic attack) Active or past history of venous thromboembolism (e.g. deep venous thrombosis, pulmonary embolism) or active thrombophlebitis Known, suspected or past history of breast cancer Known, suspected or past history of estrogen-dependent or progestin-dependent malignant neoplasia (e.g. endometrial cancer) Endometrial hyperplasia Porphyria cutanea tarda Genital bleeding Untreated hypertension Classical migraine Partial or complete loss of vision or diplopia due to ophthalmic vascular disease Presence of clinically significant screening ECG abnormalities as defined by medical judgment Presence of polyps Presence of uterine fibroids or other abnormalities affecting endometrial thickness measurement or precluding estrogen therapy Known hypersensitivity to the active substances or to any of the excipients contained in the drug products in particular to soya or peanut, as well as hereditary problems of fructose intolerance or phenylketonuria Participation in a concurrent clinical trial or another trial within the past 2 months Use of any enzyme-modifying drugs, including strong inhibitors of cytochrome P450 (CYP) enzymes (such as cimetidine, fluoxetine, quinidine, erythromycin, ciprofloxacin, fluconazole, ketoconazole, diltiazem and HIV antivirals) and strong inducers of CYP enzymes (such as barbiturates, carbamazepine, glucocorticoids, phenytoin, rifampin and St John's Wort), in the previous 28 days before day 1 of this study Maintenance therapy with any drug or significant history of drug dependency, drug abuse or alcohol abuse within the last 2 years Presence of any medical condition or other circumstances which would significantly decrease the chance of obtaining reliable data, achieving study objectives or completing the study Serious psychiatric problems (whether or not receiving treatment) or in any case such as to compromise the patient's reliability Any clinically significant illness in the previous 28 days before day 1 of this study Any history of tuberculosis and/or prophylaxis for tuberculosis Positive screening of alcohol and/or drugs of abuse Positive results to HIV Ag/Ab combo, hepatitis B surface antigen or hepatitis C virus tests Females who are pregnant according to a positive serum pregnancy test Presumption of subject's poor reliability/cooperation Any reason which, in the opinion of the Investigator, would prevent the subject from participating in the study

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: progesterone 5 mg<br>progesterone 5 mg tablet | Drug: Progesterone<br>* comparison of different dosages of drug towards the active comparator<br>|
| Experimental: progesterone 10 mg<br>progesterone 10 mg tablet | Drug: Progesterone<br>* comparison of different dosages of drug towards the active comparator<br>|
| Experimental: progesterone 20 mg<br>progesterone 20 mg tablet | Drug: Progesterone<br>* comparison of different dosages of drug towards the active comparator<br>|
| Active Comparator: progesterone 100 mg<br>progesterone 100 mg capsule | Drug: Progesterone<br>* comparison of different dosages of drug towards the active comparator<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| endometrial thickness change towards baseline (mm) |  | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| histological assessment of the endometrium (presence of hyperplasia or proliferation) |  | 3 months | 
| bleeding (presence or absence) |  | everyday over 3 months | 
| quality of life (MENQOL Questionnaire) |  | 3 months | 
| sleep scale from the Medical Outcomes Study (MOS) |  | 3 months |