Pharmacokinetics
Conditions
Keywords
PK, Pharmacokinetics
Brief summary
Study to evaluate the PK of 25 mg and 50 mg of Proellex from 2 different suppliers in the fed and fasting states.
Detailed description
This study is intended to evaluate the pharmacokinetic properties of two doses (25 mg and 50 mg) of Proellex® formulated with microcrystalline cellulose (MCC) from 2 different suppliers in the fed and fasting states.
Interventions
DRUGProellex
25 mg capsule administered once orally after subjects have been fed; 25 mg capsule administered once orally while subjects are fasting; 2, 25 mg capsules administered once orally after subjects have been fed; 2, 25 mg capsules administered once orally while subjects are fasting; and 2, 25 mg capsules administered once orally while subjects are fasting
Sponsors
Repros Therapeutics Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
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 in English on an Institutional Review Board (IRB) * 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 * Medically normal subjects with no significant abnormal findings at the screening physical examination as evaluated by the Principal Investigator that would interfere with the subject participating this study * Must have agreed to not attempt to become pregnant at any time during study participation or for 30 days thereafter * Other inclusion criteria may apply
Exclusion criteria
* Symptomatic uterine fibroids or endometriosis * Past or present history of any significant cardiovascular, renal, or hepatic disease requiring ongoing medical therapy or clinical intervention * Past or present history of thrombophlebitis, thromboembolic disorders, or cerebrovascular accident * Abnormal screening visit vital signs or clinical laboratory evaluation considered clinically significant by the Principal Investigator * Significant organ abnormality or disease (based on the Principal Investigator's judgment) that would in the opinion of the Principal Investigator exclude the subject from participating * Other
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cmax of Proellex | Up to 72 hours post-dose | Maximum observed concentration of Proellex |
| AUC0-last of Proellex | Up to 72 hours post dose | Area under the plasma concentration curve from time 0 to the last measurable plasma concentration time point, up to 72 hours. |
| Tmax of Proellex | Up to 72 hours post dose | Time to maximum plasma occurrence of Cmax |
| AUC0-infinity of Proellex | Up to 72 hours post dose | 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 | Up to 72 hours post dose | Time to maximum plasma occurrence of T1/2, calculated as ln(2)/Elimination rate constant. |
Countries
United States
Participant flow
Recruitment details
Of the 17 participants, 4 did not meet inclusion/exclusion criteria, and 1 participant enrolled as a spare was not needed, resulting in their involvement in the study being terminated. The remaining 12 participants completed all five study treatments of Proellex.
Pre-assignment details
Each of the 12 participants were randomly assigned a unique sequence of the following 5 following open-label treatments of Proellex * 25 mg formulated with AMCC (fed state) * 25 mg formulated with AMCC (fasting state) * 50 mg formulated with AMCC (fed state) * 50 mg formulated with AMCC (fasting state) * 50 mg formulated with SMCC (fasting state)
Participants by arm
| Arm | Count |
|---|---|
| All Subjects All subjects enrolled | 12 |
| Total | 12 |
Baseline characteristics
| Characteristic | All Subjects |
|---|---|
| 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 | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 1 / 12 | 2 / 12 | 4 / 12 | 7 / 12 | 5 / 12 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 | 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: Up to 72 hours post dose
Population: All 12 subjects received each treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 25 mg AMCC Fed | AUC0-infinity of Proellex | 7039.8 ng/mL*hour | Standard Deviation 3715.6 |
| 25 mg AMCC Fasting | AUC0-infinity of Proellex | 6897.0 ng/mL*hour | Standard Deviation 4440.7 |
| 50 mg AMCC Fed | AUC0-infinity of Proellex | 13014.9 ng/mL*hour | Standard Deviation 6753.2 |
| 50 mg AMCC Fasting | AUC0-infinity of Proellex | 11271.6 ng/mL*hour | Standard Deviation 6726.6 |
| 50 mg SMCC Fasting | AUC0-infinity of Proellex | 11804.8 ng/mL*hour | Standard Deviation 7186.9 |
Primary
AUC0-last of Proellex
Area under the plasma concentration curve from time 0 to the last measurable plasma concentration time point, up to 72 hours.
Time frame: Up to 72 hours post dose
Population: All 12 subjects received each treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 25 mg AMCC Fed | AUC0-last of Proellex | 6142.1 ng/mL*hour | Standard Deviation 2845.9 |
| 25 mg AMCC Fasting | AUC0-last of Proellex | 5765.7 ng/mL*hour | Standard Deviation 3036.6 |
| 50 mg AMCC Fed | AUC0-last of Proellex | 11094.2 ng/mL*hour | Standard Deviation 4209 |
| 50 mg AMCC Fasting | AUC0-last of Proellex | 9252.0 ng/mL*hour | Standard Deviation 4217.5 |
| 50 mg SMCC Fasting | AUC0-last of Proellex | 9576.2 ng/mL*hour | Standard Deviation 4328.3 |
Primary
Cmax of Proellex
Maximum observed concentration of Proellex
Time frame: Up to 72 hours post-dose
Population: 12 subjects received all 5 treatments
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 25 mg AMCC Fed | Cmax of Proellex | 485.6 ng/mL | Standard Deviation 151.3 |
| 25 mg AMCC Fasting | Cmax of Proellex | 876.7 ng/mL | Standard Deviation 201.9 |
| 50 mg AMCC Fed | Cmax of Proellex | 912.9 ng/mL | Standard Deviation 157.6 |
| 50 mg AMCC Fasting | Cmax of Proellex | 1322.5 ng/mL | Standard Deviation 154.5 |
| 50 mg SMCC Fasting | Cmax of Proellex | 1346.7 ng/mL | Standard Deviation 148.5 |
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: Up to 72 hours post dose
Population: All 12 subjects received each treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 25 mg AMCC Fed | Terminal Elimination Half-life (T1/2) of Proellex | 22.1 Hours | Standard Deviation 8.2 |
| 25 mg AMCC Fasting | Terminal Elimination Half-life (T1/2) of Proellex | 25.2 Hours | Standard Deviation 10.4 |
| 50 mg AMCC Fed | Terminal Elimination Half-life (T1/2) of Proellex | 23.8 Hours | Standard Deviation 10.8 |
| 50 mg AMCC Fasting | Terminal Elimination Half-life (T1/2) of Proellex | 26.7 Hours | Standard Deviation 11.8 |
| 50 mg SMCC Fasting | Terminal Elimination Half-life (T1/2) of Proellex | 27.5 Hours | Standard Deviation 11.9 |
Primary
Tmax of Proellex
Time to maximum plasma occurrence of Cmax
Time frame: Up to 72 hours post dose
Population: All 12 subjects received each treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 25 mg AMCC Fed | Tmax of Proellex | 2.6 Hours | Standard Deviation 0.6 |
| 25 mg AMCC Fasting | Tmax of Proellex | 0.8 Hours | Standard Deviation 0.2 |
| 50 mg AMCC Fed | Tmax of Proellex | 2.6 Hours | Standard Deviation 1 |
| 50 mg AMCC Fasting | Tmax of Proellex | 0.9 Hours | Standard Deviation 0.4 |
| 50 mg SMCC Fasting | Tmax of Proellex | 0.7 Hours | Standard Deviation 0.2 |