Open-Label, Multiple-Dose, Non-Randomized Study to Assess Drug-Drug Interactions of Proellex® in Female Subjects
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: All subjects Proellex 50 mg CYP1A2 probe CYP2C9 probe CYP2C19 probe CYP2D6 probe CYP3A4 probe |
Drug: Proellex
2, 25 mg Proellex capsules administered daily
Other Names:
Drug: CYP1A2 probe
Caffeine (200 mg)
Other Names:
Drug: CYP2C9 probe
Tolbutamide (250 mg)
Other Names:
Drug: CYP2C19 probe
Omeprazole (20 mg)
Other Names:
Drug: CYP2D6 probe
Dextromethorphan (30 mg)
Other Names:
Drug: CYP3A4 probe
Midazolam (2mg)
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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.
Eligibility Criteria
Criteria
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"
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Clinical Research Center Advanced Biomedical Research Inc. | Hackensack | New Jersey | United States | 07601 |
Sponsors and Collaborators
- Repros Therapeutics Inc.
Investigators
- Study Director: Ronald Wiehle, PhD, Repros Therapeutics Inc.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- ZP-007
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | All Participants |
|---|---|
| Arm/Group Description | CYP1A2, Day 8 relative to Day 1 AUC (caffeine probe) CYP2C19, Day 8 relative to Day 1 AUC (omeprazole probe) CYP 2C9, Day 8 relative to Day 1 AUC (tolbutamide probe) CYP2D6, Day 8 relative to Day 1 AUC (dextromethorphan probe) CYP3A4, Day 8 relative to Day 1 AUC (midazolam probe) |
| Period Title: Overall Study | |
| STARTED | 18 |
| COMPLETED | 18 |
| NOT COMPLETED | 0 |
Baseline Characteristics
| Arm/Group Title | All Subjects |
|---|---|
| Arm/Group Description | Proellex 50 mg Proellex: 2, 25 mg Proellex capsules administered daily |
| Overall Participants | 18 |
| Age (years) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [years] |
33.4
(8.3)
|
| Sex: Female, Male (Count of Participants) | |
| Female |
18
100%
|
| Male |
0
0%
|
| Region of Enrollment (participants) [Number] | |
| United States |
18
100%
|
Outcome Measures
| Title | Plasma AUC Ratio of Day 1 and Day 8 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | CYP1A2 | CYP2C9 | CYP2C19 | CYP2D6 | CYP3A4 |
|---|---|---|---|---|---|
| Arm/Group Description | Day 8 relative to Day 1 AUC (caffeine probe) | Day 8 relative to Day 1 AUC (tolbutamide probe) | Day 8 relative to Day 1 AUC (omeprazole probe) | Day 8 relative to Day 1 AUC (dextromethorphan probe) | Day 8 relative to Day 1 AUC (midazolam probe) |
| Measure Participants | 17 | 17 | 17 | 17 | 17 |
| Mean (90% Confidence Interval) [Ratio of geometric means Day 8 to Day 1] |
1.093
|
1.029
|
1.104
|
1.914
|
2.245
|
Adverse Events
| Time Frame | ||
|---|---|---|
| Adverse Event Reporting Description | ||
| Arm/Group Title | All Subjects | |
| Arm/Group Description | Proellex 50 mg Proellex: 2, 25 mg Proellex capsules administered daily | |
All Cause Mortality |
||
| All Subjects | ||
| Affected / at Risk (%) | # Events | |
| Total | / (NaN) | |
Serious Adverse Events |
||
| All Subjects | ||
| Affected / at Risk (%) | # Events | |
| Total | 0/18 (0%) | |
Other (Not Including Serious) Adverse Events |
||
| All Subjects | ||
| Affected / at Risk (%) | # Events | |
| Total | 13/18 (72.2%) | |
| Gastrointestinal disorders | ||
| Loose stools | 2/18 (11.1%) | 2 |
| Epigastric pain | 1/18 (5.6%) | 1 |
| Lower abdominal cramps | 1/18 (5.6%) | 1 |
| Heartburn | 1/18 (5.6%) | 1 |
| Musculoskeletal and connective tissue disorders | ||
| Lower back pain | 2/18 (11.1%) | 2 |
| Bilateral leg cramps | 2/18 (11.1%) | 2 |
| Bilateral foot cramps | 1/18 (5.6%) | 1 |
| Back pain | 1/18 (5.6%) | 1 |
| Nervous system disorders | ||
| Headache | 3/18 (16.7%) | 3 |
| Dizziness | 5/18 (27.8%) | 5 |
| Psychiatric disorders | ||
| Restlessness | 1/18 (5.6%) | 1 |
| Reproductive system and breast disorders | ||
| Early menstruation | 5/18 (27.8%) | 5 |
| Vaginal spotting | 1/18 (5.6%) | 1 |
| Menstrual cramps | 1/18 (5.6%) | 1 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Prior to publication, Investigator shall submit to the Sponsor a copy of any proposed publication. Sponsor shall have sixty (60) days to review the proposed publication for possible disclosure of Sponsor's Confidential Information and, upon request of Sponsor, Investigator shall delete any of Sponsor's Confidential Information or withhold submission of such publication to allow Sponsor to protect its intellectual property rights
Results Point of Contact
| Name/Title | Jennifer Wike |
|---|---|
| Organization | Repros Therapeutics Inc. |
| Phone | 281-719-3402 |
| jwike@reprosrx.com |
- ZP-007