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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Mifepristone

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33126
      • SeaView Reserch

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; Mifepristone 300 MG, 1 tablet	Drug: Mifepristone; 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; Other Names: rifampin
Experimental: Cohort 2; Mifepristone 1500 MG, 5 tablets	Drug: Mifepristone; 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; Other Names: rifampin

What is the study measuring?

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	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

Collaborators and Investigators

• Sponsor: Corcept Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): August 16, 2017
• Primary Completion (Actual): November 29, 2017
• Study Completion (Actual): November 29, 2017

Study Registration Dates

• First Submitted: August 21, 2017
• First Submitted That Met QC Criteria: August 22, 2017
• First Posted (Actual): August 23, 2017

Study Record Updates

• Last Update Posted (Actual): February 23, 2018
• Last Update Submitted That Met QC Criteria: February 21, 2018
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Anti-Bacterial Agents; Leprostatic Agents; Hormone Antagonists; Cytochrome P-450 Enzyme Inducers; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptives, Oral; Contraceptive Agents, Female; Cytochrome P-450 CYP3A Inducers; Contraceptives, Oral, Synthetic; Antitubercular Agents; Abortifacient Agents; Antibiotics, Antitubercular; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 CYP2C8 Inducers; Cytochrome P-450 CYP2C19 Inducers; Cytochrome P-450 CYP2C9 Inducers; Luteolytic Agents; Abortifacient Agents, Steroidal; Contraceptives, Postcoital, Synthetic; Contraceptives, Postcoital; Menstruation-Inducing Agents; Rifampin; Mifepristone
• Other Study ID Numbers: C1073-37

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No