Open-Label, Multiple-Dose, Non-Randomized Study to Assess Drug-Drug Interactions of Proellex® in Female Subjects

Study Overview
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Brief Summary
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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
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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.

Official Title
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An Open-Label, Multiple-Dose, Non-Randomized Study to Assess the Drug-Drug Interactions of Proellex® (CDB-4124) With Cytochrome P450 Isoenzymes CYP1A2, 2C9, 2C19, 2D6, and 3A4 in Healthy Female Subjects

Conditions
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Drug Interactions

Intervention / Treatment
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* Drug: Proellex
* Drug: CYP1A2 probe
* Drug: CYP2C9 probe
* Drug: CYP2C19 probe
* Drug: CYP2D6 probe
* Drug: CYP3A4 probe


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 48 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: All subjects<br>Proellex 50 mg CYP1A2 probe CYP2C9 probe CYP2C19 probe CYP2D6 probe CYP3A4 probe | Drug: Proellex<br>* 2, 25 mg Proellex capsules administered daily<br>* Other names: Telapristone acetate;Drug: CYP1A2 probe<br>* Caffeine (200 mg)<br>* Other names: Caffeine (200 mg);Drug: CYP2C9 probe<br>* Tolbutamide (250 mg)<br>* Other names: Tolbutamide (250 mg);Drug: CYP2C19 probe<br>* Omeprazole (20 mg)<br>* Other names: Omeprazole (20 mg);Drug: CYP2D6 probe<br>* Dextromethorphan (30 mg)<br>* Other names: Dextromethorphan (30 mg);Drug: CYP3A4 probe<br>* Midazolam (2mg)<br>* Other names: Midazolam (2mg);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 8 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Drug-drug interactions, DDI