Amenorrhea
Conditions
Keywords
Liver Function, Steady State Exposure
Brief summary
The purpose of this study is to determine the effects of five different doses of Proellex on menses, ovulation, liver function, and steady state exposure in women of reproductive age.
Detailed description
A phase I/II, 5 arm, single blind study, comparing five doses of Proellex to matching placebo in healthy adult female subjects of reproductive age. Exposure to study drug will be for up to 10 weeks. In-clinic pharmacokinetic (PK) assessments will be made on the first day of dosing and on the last day (week 10). Office visits will occur every week to assess liver function and trough blood concentrations for Proellex and primary metabolite. Daily vaginal bleeding diaries will be maintained during the course of the study. A single blind run-in period of up to 56 days will begin the study to assess baseline menstrual patterns will be utilized. Twelve subjects per treatment group (total 60 subjects) will be assigned to each dose. New groups will not begin dosing until the previous dose group has completed. Daily treatments will be either 1 mg, 3 mg, 6 mg, 9 mg, 12 mg Proellex. A single blind run-in period using placebo will be incorporated to establish baseline parameters.
Interventions
DRUGProellex
1 capsule 1x/day of 1 mg(ARM1), 3 mg(ARM2), 6 mg(ARM3), 9 mg(ARM4) or 12 mg(ARM5)
Sponsors
Repros Therapeutics Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
* Ability to understand and provide a written informed consent. * Healthy adult females between 18 and 50 years of age. Included in this group are women with the following conditions, not currently receiving drug treatment: * Excessive menstrual bleeding; * Menstrual pain; * Confirmed uterine fibroids; and * Confirmed endometriosis * Normal menstrual cycle of 26-32 days * Agree not to attempt to become pregnant * Agree to limit alcohol consumption to no more than 2 drinks per week and to avoid alcohol consumption within 48 hours of each visit * Ability to swallow gelatin capsules Ability to complete a daily subject diary * Willing to discontinue hormonal contraceptives and consent to use of double barrier contraceptive techniques over the course of the study. * Has a negative pregnancy test at the Screening and Baseline visits An exception for the pregnancy test requirement will be granted for subjects reporting surgical sterilization in medical history * A Body Mass Index (BMI) between 18 and 39 inclusive * Is available for all treatment and follow-up visits
Exclusion criteria
* Subject is a post-menopausal woman, defined as either; six (6) months or more (immediately prior to screening visit) without a menstrual period, or prior hysterectomy and/or oophorectomy * Subject is pregnant or lactating or is attempting or expecting to become pregnant during the 7 month study period * Women with abnormal liver enzymes or liver disease. * Subject previously participated in Proellex clinical trials: ZPE-201, ZPU-003, ZPU-301, ZPU-302, ZPU-303, ZPU-304, ZPU-305, and ZPU-307. * Received an investigational drug in the 30 days prior to the screening for this study * Women with a history of PCOS * Concurrent use of any testosterone, progestin, androgen, estrogen, anabolic steroids, DHEA or hormonal products for at least 2 weeks prior to screening and during the study. * Use of oral contraceptives or hormone releasing IUDs in the preceding 30 days. Use of Depo-Provera® in the preceding 6 months. * Women currently using narcotics * Women currently taking cimetidine or spironolactone * Clinically significant abnormal findings on screening examination or any condition which in the opinion of the investigator would interfere with the participant's ability to comply with the study instructions or endanger the participant if she took part in the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Induction Amenorrhea | 10 weeks | Induction of amenorrhea as determined by suppression of ovulation and/or menses, measured by using ovulation timing kits and daily diary for bleeding. Five doses will be compared in an escalating-dose, to independent groups, to a run-in placebo treatment period. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| ARM 1 1 mg Proellex
Proellex: 1 capsule 1x/day of 1 mg(ARM1), 3 mg(ARM2), 6 mg(ARM3), 9 mg(ARM4) or 12 mg(ARM5) | 12 |
| ARM 2 3 mg Proellex
Proellex: 1 capsule 1x/day of 1 mg(ARM1), 3 mg(ARM2), 6 mg(ARM3), 9 mg(ARM4) or 12 mg(ARM5) | 10 |
| ARM 3 6 mg Proellex
Proellex: 1 capsule 1x/day of 1 mg(ARM1), 3 mg(ARM2), 6 mg(ARM3), 9 mg(ARM4) or 12 mg(ARM5) | 12 |
| ARM 4 9 mg Proellex
Proellex: 1 capsule 1x/day of 1 mg(ARM1), 3 mg(ARM2), 6 mg(ARM3), 9 mg(ARM4) or 12 mg(ARM5) | 12 |
| ARM 5 12 mg proellex
Proellex: 1 capsule 1x/day of 1 mg(ARM1), 3 mg(ARM2), 6 mg(ARM3), 9 mg(ARM4) or 12 mg(ARM5) | 12 |
| Total | 58 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Unable to make scheduled visits | 1 | 0 | 4 | 0 | 1 |
Baseline characteristics
| Characteristic | ARM 1 | ARM 2 | ARM 3 | ARM 4 | ARM 5 | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 37.4 years STANDARD_DEVIATION 7.8 | 38.5 years STANDARD_DEVIATION 7.6 | 37.1 years STANDARD_DEVIATION 8.6 | 34.4 years STANDARD_DEVIATION 8.3 | 36.3 years STANDARD_DEVIATION 7 | 36.7 years STANDARD_DEVIATION 7.8 |
| Region of Enrollment United States | 12 participants | 10 participants | 12 participants | 12 participants | 12 participants | 58 participants |
| Sex: Female, Male Female | 12 Participants | 10 Participants | 12 Participants | 12 Participants | 12 Participants | 58 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 8 / 12 | 6 / 10 | 7 / 12 | 11 / 12 | 11 / 12 |
| serious Total, serious adverse events | 0 / 12 | 0 / 10 | 1 / 12 | 0 / 12 | 0 / 12 |
Outcome results
Primary
Induction Amenorrhea
Induction of amenorrhea as determined by suppression of ovulation and/or menses, measured by using ovulation timing kits and daily diary for bleeding. Five doses will be compared in an escalating-dose, to independent groups, to a run-in placebo treatment period.
Time frame: 10 weeks
Population: Per protocol: subjects who exhibited trough levels of proellex on at least 7 of the 10 weekly visits during the dosing period
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ARM 1 | Induction Amenorrhea | 2 participants |
| ARM 2 | Induction Amenorrhea | 9 participants |
| ARM 3 | Induction Amenorrhea | 6 participants |
| ARM 4 | Induction Amenorrhea | 8 participants |
| ARM 5 | Induction Amenorrhea | 6 participants |