Mifepristone Drug-Drug Interaction Study With CYP3A Inhibitor

Study Overview
=================
Brief Summary
-----------------
This is a Phase 1, single-center, fixed-sequence, open label, drug-drug interaction study of the effect of multiple daily doses of oral itraconazole 200 mg, a strong inhibitor of CYP3A, given with mifepristone 900 mg QD, in healthy male subjects, where all drug administrations are given after a meal.

Official Title
-----------------
A Phase 1, Open-Label, Drug-Drug Interaction Study in Healthy Subjects to Determine the Effects of a Strong Inhibitor (Itraconazole) of Cytochrome P450 3A on Exposure to Mifepristone and Its Metabolites

Conditions
-----------------
Healthy, Drug Interaction Potentiation

Intervention / Treatment
-----------------
* Drug: Mifepristone 300 MG
* Drug: Itraconazole 100 MG


Participation Criteria
=================
Eligibility Criteria
-----------------
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 Exclusion Criteria: Have multiple drug allergies, or be allergic to any of the components of mifepristone or itraconazole Have a condition that could be aggravated by glucocorticoid blockade (eg, asthma, any chronic inflammatory condition) In the 1 year before study drug administration, have a history of drug or alcohol abuse In the 6 calendar months before study drug administration, on average Have smoked more than 5 cigarettes/day Have consumed more than 21 units of alcohol/week (1 unit/drink = 5 ounces of wine, or 12 ounces of beer, or 1.5 ounces of hard liquor) In 2 months prior to study drug administration, have donated/lost blood or plasma in excess of 400 mL In the 30 days before study drug administration, have participated in another clinical trial of a new chemical entity or a prescription medicine

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

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1<br>Mifepristone 300 MG alone or Mifepristone 300 MG with Itraconazole 100 MG will be administered. | Drug: Mifepristone 300 MG<br>* mifepristone 300 MG (4 tablets) orally for a total of 1200 mg a day for 14 days; then mifepristone 300 mg (3 tablets) orally for a total of 900 mg a day for 28 days<br>Drug: Itraconazole 100 MG<br>* itraconazole 100 MG (2 capsules) orally for a total of 200 MG for the last 14 days of mifepristone dosing<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax of mifepristone at Day 42 compared to Day 28 | Maximum (peak) plasma drug concentration (Cmax) | Day 42 compared to Day 28 | 
| AUC0-24 of mifepristone at Day 42 compared to Day 28 | Area under the plasma concentration-time curve from zero to 24 hours (AUC0-24) | Day 42 compared to Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax of mifepristone at Day 42 compared to Day 14 |  | Day 42 compared to Day 14 | 
| AUC0-24 of mifepristone compared to Day 14 |  | Day 42 compared to Day 14 | 
| T1/2 of mifepristone | Elimination half-life (T1/2) | Days 14 and 28 | 
| Ctrough of mifepristone | Trough plasma concentration (measured concentration at the end of a dosing interval at steady state [taken directly before next administration]) (Ctrough) | Days 1 through 28 |