Drug-drug Interaction Study With MDV3100 (ASP9785) and Gemfibrozil and Itraconazole

Sponsor

Astellas Pharma Europe B.V. (Industry)

Overall Status

Completed

CT.gov ID

NCT01913379

Collaborator

Medivation, Inc. (Industry)

Enrollment

Location

Arms

Duration (Months)

10.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Healthy Subjects Pharmacokinetics Drug-Drug Interaction	Drug: MDV3100 Drug: Gemfibrozil Drug: Itraconazole	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

41 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

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 Start Date :

Aug 1, 2011

Actual Primary Completion Date :

Dec 1, 2011

Actual Study Completion Date :

Dec 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1: MDV3100	Drug: MDV3100 Oral Other Names: ASP9785 Xtandi enzalutamide
Experimental: 2: MDV3100 and gemfibrozil	Drug: MDV3100 Oral Other Names: ASP9785 Xtandi enzalutamide Drug: Gemfibrozil Oral
Experimental: 3: MDV3100 and itraconazole	Drug: MDV3100 Oral Other Names: ASP9785 Xtandi enzalutamide Drug: Itraconazole Oral

Arm

Intervention/Treatment

Experimental: 1: MDV3100

Drug: MDV3100

Oral

Other Names:

ASP9785

Xtandi

enzalutamide

Experimental: 2: MDV3100 and gemfibrozil

Drug: MDV3100

Oral

Other Names:

ASP9785

Xtandi

enzalutamide

Drug: Gemfibrozil

Oral

Experimental: 3: MDV3100 and itraconazole

Drug: MDV3100

Oral

Other Names:

ASP9785

Xtandi

enzalutamide

Drug: Itraconazole

Oral

Outcome Measures

Primary Outcome Measures

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

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 Years

Sexes Eligible for Study:

Male

Accepts 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.