Drug-Drug Interaction, Healthy Subjects, Pharmacokinetics
Conditions
Keywords
Phase 1, MDV3100, Gemfibrozil, Itraconazole, Xtandi, enzalutamide
Brief summary
A study to assess possible drug-drug interactions between MDV3100 and gemfibrozil and MDV3100 and Itraconazole.
Interventions
Sponsors
Medivation, Inc.
Astellas Pharma Europe B.V.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Body weight of at least 65.0 kg and no greater than 85.0 kg. * Body Mass Index (BMI) of at least 18.5 and no greater than 30.0 kg/m2.
Exclusion criteria
* Known or suspected hypersensitivity to MDV3100, itraconazole, gemfibrozil, any components of the formulations used, or any history of liver toxicity with other drugs. * Confirmed CYP2C8 PM status based on genotyping analysis. * Any of the liver function tests above the upper limit of normal. A retest to confirm the result may be performed once. * History of seizure, including any febrile seizure, loss of consciousness, or transient ischemia attack within 12 months prior to enrollment (Day 1 visit), or any condition that may pre-dispose to seizure (e.g., prior stroke, brain arteriovenous malformation, head trauma with loss of consciousness requiring hospitalization). * Any clinically significant history of asthma, eczema, any other allergic condition or previous severe hypersensitivity to any drug (excluding non-active hay fever). * Abnormal pulse and/or blood pressure (BP) measurements at the pre-study visit as follows: Pulse \<40 or \>90 bpm; mean systolic BP \>140 mmHg ; mean diastolic BP \>90 mmHg (BP measurements taken in triplicate after subject has been resting in supine position for 5 min; pulse will be measured automatically). * A QTc interval of \>430 ms after repeated measurements (consistently after duplicate measurements), a history of unexplained syncope, cardiac arrest, unexplained cardiac arrhythmias or torsades de pointes, structural heart disease, or a family history of Long QT Syndrome (LQTS). * Regular use of any inducer of metabolism (e.g. barbiturates, rifampin) in the 3 months prior to admission to the Clinical Unit. * Positive serology test for HBsAg, anti HAV (IgM), anti-HCV or anti-HIV 1+2.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Assessment of pharmacokinetic profile of MDV3100 by Cmax (Maximum concentration) | Day 1 through Day 53 (29 times) |
| Assessment of pharmacokinetic profile of MDV3100 by AUCinf (AUC extrapolated to infinity) | Day 1 through Day 53 (29 times) |
| Assessment of pharmacokinetic profile of MDV3100 by AUC0-432h (AUC from the time of dosing to 432 hours post-dose) | Day 1 through Day 53 (29 times) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Assessment of pharmacokinetic profile of MDV3100 | Day 1 through Day 53 (29 times) | tmax (Time to attain Cmax), t1/2 (Apparent terminal elimination half life), Vz/F (Apparent volume of distribution during the terminal phase after extra vascular dosing) and CL/F(Apparent total body clearance after extra vascular dosing) |
| Assessment of pharmacokinetic profile of the metabolites MDPC0001 and MDPC0002 | Day 1 through Day 53 (29 times) | Cmax, AUC0-432h, tmax, t1/2, and AUC0-inf |
| Safety as assessed by recording adverse events, laboratory assessments, vital signs and electrocardiograms (ECGs) | Day 1 through Day 53 | In arm 3, liver function tests (AST, ALT, GGT, total bilirubin) will be done regularly during itraconazole dosing |
| Assessment of itraconazole and hydroxyitraconazole (Arm 3) | Day 1 through Day 53 (50 times) | Cmax, C0h, Cmin, tmax, AUCtau |
| Assessment of metabolite-to-parent ratios for MDV3100 | Day 1 through Day 53 (29 times) | This may additionally be reported to assess effects on particular enzyme pathways |
| Assessment of Gemfibrozil and gemfibrozil 1-O-β-glucuronide (Arm 2) | Day 1 through Day 53 (50 times) | Cmax, C0h, Cmin, tmax, AUCtau |
Countries
France
Outcome results
None listed