Drug-drug Interaction Study With MDV3100 (ASP9785) and Gemfibrozil and Itraconazole
Phase 1
Completed
- Conditions
- Healthy SubjectsPharmacokineticsDrug-Drug Interaction
- Interventions
- Registration Number
- NCT01913379
- Lead Sponsor
- Astellas Pharma Europe B.V.
- Brief Summary
A study to assess possible drug-drug interactions between MDV3100 and gemfibrozil and MDV3100 and Itraconazole.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 41
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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 3: MDV3100 and itraconazole MDV3100 - 3: MDV3100 and itraconazole Itraconazole - 2: MDV3100 and gemfibrozil MDV3100 - 1: MDV3100 MDV3100 - 2: MDV3100 and gemfibrozil Gemfibrozil -
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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
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
Assessment of itraconazole and hydroxyitraconazole (Arm 3) Day 1 through Day 53 (50 times) Cmax, C0h, Cmin, tmax, AUCtau
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
Trial Locations
- Locations (1)
SGS
🇫🇷Paris, France