MLE4901 vs. Placebo for the Treatment of PCOS

Study Overview
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Brief Summary
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This is a Phase 2b double-blind, randomized, parallel-group, placebo-controlled study of MLE4901 versus placebo in women with PCOS.

Detailed Description
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Following a Screening/Wash-out Period of up to 12 weeks, an 8-week Lead-in Period (starting with a progestin challenge) will be used to better characterize the study population. A Treatment Period of 28 weeks' duration will follow the Lead-in Period. Then, an 8-week Follow-up Period (i.e., no study drug) will be used to assess the durability of effects of MLE4901. The study duration will be approximately 48 weeks (11 months) per subject

Official Title
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A Double-blind, Randomized, Parallel-group, Placebo-controlled Study of MLE4901 for the Treatment of Polycystic Ovary Syndrome (PCOS)

Conditions
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Polycystic Ovary Syndrome (PCOS)

Intervention / Treatment
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* Drug: MLE4901
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Oligo-/amenorrhea At least one of the following during Screening: Clinical signs of hyperandrogenism, where clinical hyperandrogenism may include hirsutism (defined as excessive terminal hair that appears in a male pattern), acne, or androgenic alopecia Biochemical hyperandrogenism refers to an elevated serum androgen level (i.e., total, bioavailable or free testosterone level ≥ULN) Polycystic ovarian morphology, defined as the presence of 12 or more follicles 2-9 mm in diameter and/or an increased ovarian volume >10 mL (without a cyst or dominant follicle) in either ovary Body mass index (BMI) 22 to 45 kg/m2, inclusive Must be willing to avoid use of all hair removal procedures and products during study participation Must be willing to avoid all prescription treatments for acne and not increase the dose or frequency of their current non-prescription acne treatment regimen during study participation Must be willing to avoid the use of all hair growth procedures and products during study participation Permanently surgically sterilized (bilateral salpingectomy or tubal occlusion) >2 years or male partner(s) has had a vasectomy >2 years or must consent to use two permitted medically-acceptable methods of contraception throughout the study during any sexual intercourse with a male partner. Permitted medically-acceptable methods of birth control for this study are defined as use of a male condom plus one of the following: spermicide, diaphragm with spermicide, or an intrauterine device that does not contain steroid hormones. Exclusion Criteria: Menopausal or peri-menopausal, defined for this study as FSH (follicle stimulating hormone ) >10 IU/L Irregular vaginal/menstrual bleeding caused by conditions other than PCOS (e.g., uterine polyps or submucosal uterine fibroids) Abnormal Papanicolaou (Pap) test during Screening requiring follow-up sooner than 1 year after the test Uncontrolled hypo- or hyperthyroidism Post-hysterectomy or endometrial ablation Post-oophorectomy (unilateral or bilateral) or other ovarian surgery Medical history of type 1 or type 2 diabetes mellitus

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Plain, round, biconvex, white film-coated tablets that appear identical to MLE4901 tablets | Drug: Placebo<br>* Placebo to match active drug<br>|
| Experimental: MLE4901<br>Plain, round, biconvex, white film-coated tablets administered twice per day | Drug: MLE4901<br>* For 80% of subjects randomized to MLE4901 (n=24/30), the dose is 40 mg twice daily. Six subjects (20%) randomized to higher MLE4901 dose cohorts that were promptly discontinued.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Menstrual Cycle Duration | Assessment of the number of days between menstrual cycles (i.e., days between the start of a menstrual period and the start of the next consecutive menstrual period) from baseline to end of 28 week double blind treatment period | 28 Week double blind treatment period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Menstrual Periods | Number of menstrual periods from baseline to the end of the 28 week double blind treatment period | 28 Week double blind treatment period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acne, Hirsutism, Menstrual Irregularity, Alopecia