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

Healthy Subjects Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01913379
• Other study ID #: 9785-CL-0006
• Secondary ID: 2011-000333-37
• Status: Completed
• Phase: Phase 1
• First received: July 30, 2013
• Last updated: July 30, 2013
• Start date: August 2011
• Est. completion date: December 2011

Study information

• Verified date: July 2013
• Source: Astellas Pharma Inc
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 41
• Est. completion date: December 2011
• Est. primary completion date: December 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 55 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Drug-Drug Interaction
• Healthy Subjects
• Pharmacokinetics

Intervention

Drug:
• MDV3100
Oral
• Gemfibrozil
Oral
• Itraconazole
Oral

Locations

Country	Name	City	State
France	SGS	Paris

Sponsors (2)

Lead Sponsor	Collaborator
Astellas Pharma Europe B.V.	Medivation, Inc.

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Assessment of pharmacokinetic profile of MDV3100 by Cmax (Maximum concentration)		Day 1 through Day 53 (29 times)	No
Primary	Assessment of pharmacokinetic profile of MDV3100 by AUCinf (AUC extrapolated to infinity)		Day 1 through Day 53 (29 times)	No
Primary	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)	No
Secondary	Assessment of pharmacokinetic profile of MDV3100	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)	Day 1 through Day 53 (29 times)	No
Secondary	Assessment of pharmacokinetic profile of the metabolites MDPC0001 and MDPC0002	Cmax, AUC0-432h, tmax, t1/2, and AUC0-inf	Day 1 through Day 53 (29 times)	No
Secondary	Assessment of metabolite-to-parent ratios for MDV3100	This may additionally be reported to assess effects on particular enzyme pathways	Day 1 through Day 53 (29 times)	No
Secondary	Assessment of Gemfibrozil and gemfibrozil 1-O-ß-glucuronide (Arm 2)	Cmax, C0h, Cmin, tmax, AUCtau	Day 1 through Day 53 (50 times)	No
Secondary	Assessment of itraconazole and hydroxyitraconazole (Arm 3)	Cmax, C0h, Cmin, tmax, AUCtau	Day 1 through Day 53 (50 times)	No
Secondary	Safety as assessed by recording adverse events, laboratory assessments, vital signs and electrocardiograms (ECGs)	In arm 3, liver function tests (AST, ALT, GGT, total bilirubin) will be done regularly during itraconazole dosing	Day 1 through Day 53	No