Clinical trial NCT01913379: Drug-drug Interaction Study With MDV3100 (ASP9785) and Gemfibrozil and Itraconazole
Official title: A Phase I Randomized, Open-label, 3-arm Parallel-design Study to Determine the Effect of Multiple-dose Gemfibrozil or Itraconazole on the Pharmacokinetics, Safety and Tolerability of Single-dose MDV3100 (ASP9785) in Healthy Male Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Subjects
Pharmacokinetics
Drug-Drug Interaction
Keywords: Phase 1
MDV3100
Gemfibrozil
Itraconazole
Xtandi
enzalutamide
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
Collaborators: name: Medivation, Inc.
First posted: 2013-08-01
Enrollment: 41
Sex: MALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL

Brief summary: A study to assess possible drug-drug interactions between MDV3100 and gemfibrozil and MDV3100 and Itraconazole.


Eligibility criteria: 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.

Primary outcomes:
measure: Assessment of pharmacokinetic profile of MDV3100 by Cmax (Maximum concentration)
timeFrame: Day 1 through Day 53 (29 times)
measure: Assessment of pharmacokinetic profile of MDV3100 by AUCinf (AUC extrapolated to infinity)
timeFrame: Day 1 through Day 53 (29 times)
measure: Assessment of pharmacokinetic profile of MDV3100 by AUC0-432h (AUC from the time of dosing to 432 hours post-dose)
timeFrame: Day 1 through Day 53 (29 times)
Secondary outcomes:
measure: Assessment of pharmacokinetic profile of MDV3100
timeFrame: Day 1 through Day 53 (29 times)
measure: Assessment of pharmacokinetic profile of the metabolites MDPC0001 and MDPC0002
timeFrame: Day 1 through Day 53 (29 times)
measure: Assessment of metabolite-to-parent ratios for MDV3100
timeFrame: Day 1 through Day 53 (29 times)
measure: Assessment of Gemfibrozil and gemfibrozil 1-O-β-glucuronide (Arm 2)
timeFrame: Day 1 through Day 53 (50 times)
measure: Assessment of itraconazole and hydroxyitraconazole (Arm 3)
timeFrame: Day 1 through Day 53 (50 times)
measure: Safety as assessed by recording adverse events, laboratory assessments, vital signs and electrocardiograms (ECGs)
timeFrame: Day 1 through Day 53
Other outcomes:
Locations:
city: Paris
country: France
facility: SGS
Study officials:
affiliation: Astellas Pharma Europe B.V.
name: Operation Senior Research Manager
role: STUDY_CHAIR
References:
citation: Gibbons JA, de Vries M, Krauwinkel W, Ohtsu Y, Noukens J, van der Walt JS, Mol R, Mordenti J, Ouatas T. Pharmacokinetic Drug Interaction Studies with Enzalutamide. Clin Pharmacokinet. 2015 Oct;54(10):1057-69. doi: 10.1007/s40262-015-0283-1.