Polycystic Ovary Syndrome (PCOS)
Conditions
Keywords
Acne, Hirsutism, Menstrual Irregularity, Alopecia
Brief summary
This is a Phase 2b double-blind, randomized, parallel-group, placebo-controlled study of MLE4901 versus placebo in women with PCOS.
Detailed description
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
Interventions
DRUGMLE4901
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.
DRUGPlacebo
Placebo to match active drug
Sponsors
Medpace, Inc.
Covance
Millendo Therapeutics US, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 45 Years
Healthy volunteers
No
Inclusion criteria
1. Oligo-/amenorrhea 2. 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 3. Body mass index (BMI) 22 to 45 kg/m2, inclusive 4. Must be willing to avoid use of all hair removal procedures and products during study participation 5. 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 6. Must be willing to avoid the use of all hair growth procedures and products during study participation 7. 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
1. Menopausal or peri-menopausal, defined for this study as FSH (follicle stimulating hormone ) \>10 IU/L 2. Irregular vaginal/menstrual bleeding caused by conditions other than PCOS (e.g., uterine polyps or submucosal uterine fibroids) 3. Abnormal Papanicolaou (Pap) test during Screening requiring follow-up sooner than 1 year after the test 4. Uncontrolled hypo- or hyperthyroidism 5. Post-hysterectomy or endometrial ablation 6. Post-oophorectomy (unilateral or bilateral) or other ovarian surgery 7. Medical history of type 1 or type 2 diabetes mellitus
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Menstrual Cycle Duration | 28 Week double blind treatment period | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Menstrual Periods | 28 Week double blind treatment period | Number of menstrual periods from baseline to the end of the 28 week double blind treatment period |
Countries
United States
Participant flow
Recruitment details
The study was conducted at 30 US sites. The study was initiated on 27 July 2016 and completed on 04 August 2017. Study sites consisted of a combination of private clinical research centers, medical clinics, and academic practices.
Pre-assignment details
Prior to randomization, subjects completed a screening period with a wash-out of medications for PCOS symptoms (if needed). Eligible subjects then completed an 8-week Lead-in Period with an initial 5-day progestin challenge, self-report of menstrual bleeding, and assessment of ovulation status by urine pregnenediol-3-glucuronide.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Treatment Arm Matching placebo tablet self-administered twice daily | 25 |
| MLE4901 Treatment Arm Treatment with 1 tablet of MLE4901 self-administered twice daily \[80% treated with dose of 40 mg twice daily\] | 30 |
| Total | 55 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 4 |
| Overall Study | Dosing group discontinued | 0 | 5 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Pregnancy | 1 | 0 |
| Overall Study | Protocol Violation | 0 | 1 |
| Overall Study | Study terminated by sponsor | 23 | 18 |
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Placebo Treatment Arm | Total | MLE4901 Treatment Arm |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 25 Participants | 55 Participants | 30 Participants |
| Age, Continuous | 29.8 years STANDARD_DEVIATION 5.16 | 29.1 years STANDARD_DEVIATION 5.46 | 28.5 years STANDARD_DEVIATION 5.71 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 6 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 22 Participants | 49 Participants | 27 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Menstrual cycle frequency | 3.1 cycles/year STANDARD_DEVIATION 1.74 | 2.9 cycles/year STANDARD_DEVIATION 1.78 | 2.8 cycles/year STANDARD_DEVIATION 1.83 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 10 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 20 Participants | 44 Participants | 24 Participants |
| Region of Enrollment United States | 25 participants | 55 participants | 30 participants |
| Sex: Female, Male Female | 25 Participants | 55 Participants | 30 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 25 | 0 / 30 |
| other Total, other adverse events | 15 / 25 | 18 / 30 |
| serious Total, serious adverse events | 0 / 25 | 1 / 30 |
Outcome results
Primary
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
Time frame: 28 Week double blind treatment period
Population: The trial was terminated prior to collection of any efficacy data.
Secondary
Number of Menstrual Periods
Number of menstrual periods from baseline to the end of the 28 week double blind treatment period
Time frame: 28 Week double blind treatment period
Population: Study terminated prior to collection of efficacy data.