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

NCT01913379 | Completed Phase 1

• 2 other identifiers: 9785-CL-00062011-000333-37
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Healthy Subjects; Pharmacokinetics; Drug-Drug Interaction

Keywords

Phase 1; MDV3100; Gemfibrozil; Itraconazole; Xtandi; enzalutamide

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (6)

• Assessment of pharmacokinetic profile of MDV3100

  Day 1 through Day 53 (29 times)

• Assessment of pharmacokinetic profile of the metabolites MDPC0001 and MDPC0002

  Day 1 through Day 53 (29 times)

• Assessment of metabolite-to-parent ratios for MDV3100

  Day 1 through Day 53 (29 times)

• Assessment of Gemfibrozil and gemfibrozil 1-O-β-glucuronide (Arm 2)

  Day 1 through Day 53 (50 times)

• Assessment of itraconazole and hydroxyitraconazole (Arm 3)

  Day 1 through Day 53 (50 times)

Study Arms (3)

1: MDV3100

EXPERIMENTAL

Drug: MDV3100

2: MDV3100 and gemfibrozil

EXPERIMENTAL

Drug: MDV3100; Drug: Gemfibrozil

3: MDV3100 and itraconazole

EXPERIMENTAL

Drug: MDV3100; Drug: Itraconazole

Interventions

MDV3100 DRUG

Oral

Also known as: ASP9785, Xtandi, enzalutamide

1: MDV3100; 2: MDV3100 and gemfibrozil; 3: MDV3100 and itraconazole

Gemfibrozil DRUG

Oral

2: MDV3100 and gemfibrozil

Itraconazole DRUG

Oral

3: MDV3100 and itraconazole

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Astellas Pharma Europe B.V.: lead
• Medivation, Inc.: collaborator

Study Sites (1)

SGS

Paris, 75015, France

Location

Related Publications (1)

• 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.

  PMID: 25929560 DERIVED

MeSH Terms

Interventions

enzalutamide; Gemfibrozil; Itraconazole

Intervention Hierarchy (Ancestors)

Fibric Acids; Isobutyrates; Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Pentanoic Acids; Valerates; Phenyl Ethers; Ethers; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Fatty Acids, Volatile; Fatty Acids; Lipids; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Piperazines

Study Officials

• Operation Senior Research Manager

  Astellas Pharma Europe B.V.

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 30, 2013
• First Posted: August 1, 2013
• Study Start: August 1, 2011
• Primary Completion: December 1, 2011
• Study Completion: December 1, 2011
• Last Updated: August 1, 2013

Record last verified: 2013-07

Locations

FR (1)