Drug Interactions
Conditions
Keywords
Drug-drug interactions, DDI
Brief summary
This study will assess possible drug-drug interactions with specific isoenzymes over a total study duration of 6-8 weeks. Blood samples collected pre and post-dose, and urine samples collected post dose will be analyzed.
Detailed description
This is an open-label, multiple-dose, non-randomized study to assess the drug-drug interactions of Proellex® with cytochrome P450 isoenzymes in healthy female subjects. On Day 1, following an overnight fast and morning void of the bladder, subjects will be administered CYP probe drugs orally. Serial blood samples will be collected at pre-dose and post-dose. Subjects will be administered two Proellex® 25 mg capsules (50 mg total dose) at approximately 0800 hours on Day 2 and 0700 hours on Days 3 through 8. One hour after administration of Proellex® on Day 8, the five CYP probe drugs will be administered and blood and urine samples collected as on Day 1. Blood samples for the determination of plasma concentrations of CDB-4124 and its metabolite CDB-4453 will be collected at pre-dose (trough) on Days 6, 7, and 8 to determine if steady-state conditions have been achieved. Samples will also be collected on Day 8 at 1, 2, 8 and 24 hour after administration of Proellex® to determine the plasma concentrations of CDB-4124 and CDB-4453.
Interventions
DRUGProellex
2, 25 mg Proellex capsules administered daily
DRUGCYP1A2 probe
Caffeine (200 mg)
DRUGCYP2C9 probe
Tolbutamide (250 mg)
DRUGCYP2C19 probe
Omeprazole (20 mg)
DRUGCYP2D6 probe
Dextromethorphan (30 mg)
DRUGCYP3A4 probe
Midazolam (2mg)
Sponsors
Repros Therapeutics Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 48 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy adult females * A body mass index between 18 and 30 kg/m2, inclusive * Negative urine drug and alcohol screen .
Exclusion criteria
* Significant medical condition, * Significant physical examination finding * Clinical laboratory * ECG abnormality * CYP2D6 poor metabolizer
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Plasma AUC Ratio of Day 1 and Day 8 | 8 days | Assessment of the drug-drug interactions of Proellex® (CDB-4124) with cytochrome P450 isoenzymes CYP1A2, 2C9, 2C19, 2D6, and 3A4 in healthy female subjects administered 50 mg Proellex® once daily (QD). The Day 8 AUC was compared to the Day 1 AUC to determine inhibition. For CYP1A2 the plasma paraxanthine/caffeine MR ratio (metabolic ratio) was used. For CYP2D6 the MR ratio of dextromethorphan/dextrorphan was used. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Subjects Proellex 50 mg
Proellex: 2, 25 mg Proellex capsules administered daily | 18 |
| Total | 18 |
Baseline characteristics
| Characteristic | All Subjects |
|---|---|
| Age, Continuous | 33.4 years STANDARD_DEVIATION 8.3 |
| Region of Enrollment United States | 18 participants |
| Sex: Female, Male Female | 18 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 13 / 18 |
| serious Total, serious adverse events | 0 / 18 |
Outcome results
Primary
Plasma AUC Ratio of Day 1 and Day 8
Assessment of the drug-drug interactions of Proellex® (CDB-4124) with cytochrome P450 isoenzymes CYP1A2, 2C9, 2C19, 2D6, and 3A4 in healthy female subjects administered 50 mg Proellex® once daily (QD). The Day 8 AUC was compared to the Day 1 AUC to determine inhibition. For CYP1A2 the plasma paraxanthine/caffeine MR ratio (metabolic ratio) was used. For CYP2D6 the MR ratio of dextromethorphan/dextrorphan was used.
Time frame: 8 days
Population: One subject had concentrations of Proellex (CDB-4124 and CDB-4453) that were below the lower level of quantitation at all time points tested and was excluded from the pharmacokinetic analyses.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| CYP1A2 | Plasma AUC Ratio of Day 1 and Day 8 | 1.093 Ratio of geometric means Day 8 to Day 1 |
| CYP2C9 | Plasma AUC Ratio of Day 1 and Day 8 | 1.029 Ratio of geometric means Day 8 to Day 1 |
| CYP2C19 | Plasma AUC Ratio of Day 1 and Day 8 | 1.104 Ratio of geometric means Day 8 to Day 1 |
| CYP2D6 | Plasma AUC Ratio of Day 1 and Day 8 | 1.914 Ratio of geometric means Day 8 to Day 1 |
| CYP3A4 | Plasma AUC Ratio of Day 1 and Day 8 | 2.245 Ratio of geometric means Day 8 to Day 1 |