Healthy
Conditions
Keywords
PK, Pharmacokinetics
Brief summary
An open-label, randomized, single-center, outpatient, unblinded, single-dose, three-way crossover study of the safety and PK properties of Proellex® in women ages 18 - 34 years.
Detailed description
This is an open-label, randomized, single-center, outpatient, unblinded, single-dose, three-way crossover study of the safety and PK properties of Proellex® in women ages 18 - 34 years. Twelve female subjects will each receive a single dose of Proellex®: 25 mg (fed state, formulation A), 25 mg (fed state, formulation B), and 25 mg (fasting state, formulation B); successive dosing will be separated by at least one week intervals from the previous dosing. Blood will be collected prior to taking the dose, and following the dose for 24 hours post-dose. Subjects will be discharged from the study after the last blood sample is obtained after the third dose of Proellex®. Safety will be assessed throughout the study.
Interventions
DRUGProellex 25 mg formulation A
One Proellex 25 mg formulation A capsule
DRUGProellex 25 mg formulation B
One 25 mg Proellex capsule formulation B administered both fed and fasted
Sponsors
Repros Therapeutics Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 34 Years
Healthy volunteers
Yes
Inclusion criteria
* Subject must be able to speak, read and understand English and be willing and able to provide written informed consent on an Institutional Review Board (IRB)-approved form prior to the initiation of any study procedures. Subject must have signed and dated a written Informed Consent Form (ICF) before undergoing any study related activities, including discontinuation of any prohibited medications * Premenopausal women aged 18 - 34 inclusive with body mass index between 18 and 35 inclusive * Women of child-bearing potential must be willing to use effective non-hormonal, double-barrier method contraception during the study period and for a minimum of 30 days after discontinuation of the study medication. Women who have had a hysterectomy will be allowed into the study * Must have a negative urine pregnancy test at screening * Able to swallow gelatin capsules * In general good health * Must have agreed to not attempt to become pregnant at any time during study participation or for 30 days thereafter * Must not have used tobacco (nicotine products) for at least two years before the study starts * Must have normal (or abnormal and clinically insignificant) laboratory values at screening * Willing to remain in the clinic for the screening visit and for the treatment visits * Available for all treatment and follow-up visits * Willing to comply with all study procedures * Additional inclusion criteria may apply
Exclusion criteria
* Pregnant or lactating females or women who are attempting or expecting to become pregnant at any time during the study * Past or present history of experiencing any allergic reaction to the formulations administered in this study, or in the opinion of the Principal Investigator, suggests an increased potential for an adverse hypersensitivity * Any medical condition, which, in the judgment of the Principal Investigator, will prevent the subject from starting and/or completing the study * Past or present history of any significant cardiovascular, renal, hepatic disease, thrombophlebitis, thromboembolic disorders, or cerebrovascular accident requiring ongoing medical therapy or clinical intervention * A QTc interval of \>450ms at screening * Subject with abnormal screening visit vital signs or clinical laboratory evaluation considered clinically significant by the Principal Investigator * Subjects with symptomatic uterine fibroids or endometriosis * Use of other oral contraceptives or hormonal treatments within 30 days of first dose of study medication * Use of a hormone-releasing intrauterine device * Subject with a history of alcohol and/or drug abuse * Known active infection of HIV, Hepatitis A, B or C * Subject who has participated in a clinical trial with investigational medication within 30 days prior to study medication administration or who plans to take an experimental drug prior to the end of 30 days after participation in this study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cmax of Proellex | 24 hours | Maximum observed concentration (Cmax) of a single dose of Proellex® (25 mg) Formulation A using two different formulations of the drug in healthy adult female subjects with or without fasting |
| AUC0-last of Proellex | Up to 24 hours | Area under the plasma concentration curve from time 0 (AUC0-last) to the last measurable plasma concentration time point, up to 24 hours. |
| Tmax | 24 hours | Time to maximum plasma occurrence of Cmax |
| AUC0-infinity of Proellex | 24 hours | Area under the plasma concentration curve from time 0 to extrapolated to infinity, calculated by summing the area under the curve from time zero to the time of the last quantifiable concentration |
| Terminal Elimination Half-life (T1/2) of Proellex | 24 hours | Time to maximum plasma occurrence of T1/2, calculated as ln(2)/Elimination rate constant. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 25 mg Proellex Three different treatments of Proellex 25 mg, given in a randomized treatment sequence.
* Proellex 25 mg capsule, Formulation A, fed state.
* Proellex 25 mg Formulation B, fed state.
* Proellex 25 mg Formulation B, fasting state. | 12 |
| Total | 12 |
Baseline characteristics
| Characteristic | 25 mg Proellex |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants |
| Region of Enrollment United States | 12 participants |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 2 / 12 | 1 / 12 | 2 / 12 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 | 0 / 12 |
Outcome results
Primary
AUC0-infinity of Proellex
Area under the plasma concentration curve from time 0 to extrapolated to infinity, calculated by summing the area under the curve from time zero to the time of the last quantifiable concentration
Time frame: 24 hours
Population: All 12 participants in the Safety population are included in the Intent-to-Treat (ITT) population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Formulation A Fed | AUC0-infinity of Proellex | 6851.5 ng/mL*hour | Standard Deviation 5686.2 |
| Formulation B Fed | AUC0-infinity of Proellex | 7967.9 ng/mL*hour | Standard Deviation 7125.9 |
| Formulation B Fasted | AUC0-infinity of Proellex | 6554.0 ng/mL*hour | Standard Deviation 4350.1 |
Primary
AUC0-last of Proellex
Area under the plasma concentration curve from time 0 (AUC0-last) to the last measurable plasma concentration time point, up to 24 hours.
Time frame: Up to 24 hours
Population: ITT and Safety populations are the same
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Formulation A Fed | AUC0-last of Proellex | 6851.5 ng/mL*hour | Standard Deviation 5686.2 |
| Formulation B Fed | AUC0-last of Proellex | 7967.9 ng/mL*hour | Standard Deviation 7125.9 |
| Formulation B Fasted | AUC0-last of Proellex | 6161.8 ng/mL*hour | Standard Deviation 4364.5 |
Primary
Cmax of Proellex
Maximum observed concentration (Cmax) of a single dose of Proellex® (25 mg) Formulation A using two different formulations of the drug in healthy adult female subjects with or without fasting
Time frame: 24 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Formulation A Fed | Cmax of Proellex | 405.5 ng/mL | Standard Deviation 168.2 |
| Formulation B Fed | Cmax of Proellex | 426.7 ng/mL | Standard Deviation 158 |
| Formulation B Fasted | Cmax of Proellex | 824.2 ng/mL | Standard Deviation 351.7 |
Primary
Terminal Elimination Half-life (T1/2) of Proellex
Time to maximum plasma occurrence of T1/2, calculated as ln(2)/Elimination rate constant.
Time frame: 24 hours
Population: All 12 participants in the Safety population are included in the Intent-to-Treat (ITT) population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Formulation A Fed | Terminal Elimination Half-life (T1/2) of Proellex | 23.2 Hours | Standard Deviation 14.8 |
| Formulation B Fed | Terminal Elimination Half-life (T1/2) of Proellex | 27.3 Hours | Standard Deviation 20.7 |
| Formulation B Fasted | Terminal Elimination Half-life (T1/2) of Proellex | 19.2 Hours | Standard Deviation 9 |
Primary
Tmax
Time to maximum plasma occurrence of Cmax
Time frame: 24 hours
Population: All 12 participants in the Safety population are included in the Intent-to-Treat (ITT) population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Formulation A Fed | Tmax | 3.1 Hours | Standard Deviation 1.2 |
| Formulation B Fed | Tmax | 2.9 Hours | Standard Deviation 1.2 |
| Formulation B Fasted | Tmax | 1.0 Hours | Standard Deviation 0.5 |