Crossover Drug-Drug Interaction Study to Determine Effects of Cytochrome P450 3A on Exposure to Mifepristone and Its Metabolites

Study Overview
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Brief Summary
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This is a Phase 1, single center, fixed sequence, open label, drug-drug interaction study of the effect of multiple doses of rifampin 600 mg daily, a strong CYP3A inducer, on the exposure of mifepristone at 2 dose levels.

Official Title
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A Phase 1, Open-Label, Fixed-Sequence, Crossover Drug-Drug Interaction Study in Healthy Subjects to Determine the Effects of a Strong Inducer of Cytochrome P450 3A on Exposure to Mifepristone and Its Metabolites

Conditions
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Healthy

Intervention / Treatment
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* Drug: Mifepristone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Be healthy Have a BMI of 18 to 32 kg/m2, inclusive, and body weight more than 50 kg (110 pounds) Be judged to be in good health, based on the results of medical history, physical examination, vital signs, 12-lead ECG, and clinical laboratory findings Have suitable veins for multiple venipuncture/cannulation Female subjects of childbearing potential must use highly effective contraception with low user-dependency. The only acceptable method is an intrauterine device (IUD), provided that the subject has tolerated its use for at least 3 months before the first dose of study drug and undertakes not to have it removed for 1 month after the last dose of study drug. Use of hormonal contraception (by any route, including intrauterine hormone releasing systems) or hormone replacement therapy is NOT acceptable. Exclusion Criteria: Have multiple drug allergies, or be allergic to any of the components of mifepristone or rifampin Have a condition that could be aggravated by glucocorticoid blockade (eg, asthma, any chronic inflammatory condition) Have a history of unexplained vaginal bleeding, endometrial hyperplasia with atypia or endometrial carcinoma Breastfeeding In the 1 year before first study drug administration, have a history of drug or alcohol abuse In the 6 calendar months before first study drug administration, on average Have smoked more than 5 cigarettes/day Have consumed more than 21 units of alcohol/week for male subjects or 14 units for female subjects (1 unit/drink = 5 ounces of wine, or 12 ounces of beer, or 1.5 ounces of hard liquor) In the 2 calendar months before first study drug administration, have donated/lost blood or plasma in excess of 400 mL In the 30 days before first study drug administration, have participated in another clinical trial of a new chemical entity or a prescription medicine

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

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: Other
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>Mifepristone 300 MG, 1 tablet | Drug: Mifepristone<br>* Period 1: mifepristone 300 MG (1 tablet) for a total of 300 MG on Day 1 in Cohort 1; and mifepristone 300 MG (5 tablets) for a total of 1500 MG in Cohort 2; then Period 2: rifampin 300 MG (2 capsules) for a total of 600 MG daily for 14 days for both cohorts; then Period 3: mifepristone 300 MG (1 tablet) for a total of 300 MG on Day 1 in Cohort 1; and mifepristone 300 MG (5 tablets) for a total of 1500 MG in Cohort 2<br>* Other names: rifampin;|
| Experimental: Cohort 2<br>Mifepristone 1500 MG, 5 tablets | Drug: Mifepristone<br>* Period 1: mifepristone 300 MG (1 tablet) for a total of 300 MG on Day 1 in Cohort 1; and mifepristone 300 MG (5 tablets) for a total of 1500 MG in Cohort 2; then Period 2: rifampin 300 MG (2 capsules) for a total of 600 MG daily for 14 days for both cohorts; then Period 3: mifepristone 300 MG (1 tablet) for a total of 300 MG on Day 1 in Cohort 1; and mifepristone 300 MG (5 tablets) for a total of 1500 MG in Cohort 2<br>* Other names: rifampin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax of mifepristone of period 1 vs Cmax of mifepristone of period 3 | Maximum (peak) plasma drug concentration (Cmax) | 18 days | 
| AUC0-tz of mifepristone of period 1 vs AUC0-tz of mifepristone of period 3 | Area under the concentration-time curve from zero up to the last concentration above the lower limit of quantification of the assay (AUC0-tz) | 18 days | 
| AUCinf of mifepristone of period 1 vs AUCinf of mifepristone of period 3 | Area under the plasma concentration-time curve from time zero to infinity (AUCinf) | 18 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax of mifepristone metabolites of period 1 vs Cmax of mifepristone metabolites of period 3 |  | 18 days | 
| AUC0-tz of mifepristone metabolites of period 1 vs AUC0-tz of mifepristone metabolites of period 3 |  | 18 days | 
| AUCinf of mifepristone metabolites of period 1 vs AUCinf of minfepristone metabolites of period 3 |  | 18 days |