A Study to Assess the Effect of Abiraterone (JNJ-589485) on the Pharmacokinetics of Pioglitazone Following Administration of Abiraterone Acetate (JNJ-212082) and Pioglitazone HCl Tablets in Healthy Male Participants

An Open-Label Drug-Drug Interaction Study to Assess the Effect of Abiraterone (JNJ-589485) on the Pharmacokinetics of Pioglitazone Following Administration of Abiraterone Acetate (JNJ-212082) and Pioglitazone HCl Tablets in Healthy Male Subjects

The purpose of this study is to evaluate the effects of abiraterone on the pharmacokinetics (study of what the body does to a drug) of pioglitazone when coadministered with abiraterone acetate in healthy adult male participants.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: Pioglitazone HCl; Drug: Abiraterone acetate

Detailed Description

This is an open-label (identity of assigned study drug will be known) single-dose drug-drug interaction study to assess the effect of abiraterone on pioglitazone. Approximately 16 healthy adult male participants will be enrolled in this study. The study consists of a screening phase, an open-label treatment phase consisting of 2 single-dose treatment periods, end-of-study or withdrawal assessments done upon completion of the 72-hour pharmacokinetic sampling on Day 11 of Period 2 or upon withdrawal, and a follow-up visit 5 to 7 days after the last study procedure. The total study length is 32 days. Participants will receive pioglitazone alone on Day 1 (Period 1) of the study. On Day 8 (Period 2), participants will receive a single dose of abiraterone acetate followed by a single dose of pioglitazone one hour later. Successive pioglitazone administrations will be separated by a washout period of 7 days. Participants will be confined to the study center from Day -1 to Day 4 of Period 1 and from Day 7 to Day 11 of Period 2, at least 10 hours before each study drug administration until completion of the 72-hour blood sample collection for each period. A pharmacogenomic blood sample will be collected from all participants on Day -1. Safety will be monitored throughout the study.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Merksem, Belgium

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Agrees to protocol-defined use of effective contraception for 1 week after receiving the last dose of study drug
• Agrees to not donate sperm during the study and for 1 week after receiving the last dose of study drug
• Body mass index between 18 and 30 kg/m2 and body weight not less than 50 kg
• Blood pressure between 90 and 140 mmHg systolic, and no higher than 90 mmHg diastolic
• A 12-lead electrocardiogram consistent with normal cardiac conduction and function
• Non-smoker
• Laboratory values within protocol -defined parameters

Exclusion Criteria:

• History of or current clinically significant medical illness
• Clinically significant abnormal values for hematology, clinical chemistry, or urinalysis at screening or at admission to the study center as deemed appropriate by the investigator
• Presence of sexual dysfunction or any medical condition that would affect sexual function
• Clinically significant abnormal physical examination, vital signs, or 12-lead electrocardiogram
• Use of any prescription or nonprescription medication (including vitamins and herbal supplements) before the first dose of the study drug is scheduled through study completion
• History of drug or alcohol abuse within 3 years before screening or positive test result(s) for alcohol and/or drugs of abuse at screening and Day -1 and at Day 7 of the treatment period
• Known allergy to the study drug or any of the excipients of the formulation
• History of stomach or intestinal surgery or resection that would potentially alter absorption or excretion of orally administered drugs (appendectomy and hernia repair will be allowed)
• Donated blood or blood products or had substantial loss of blood within 3 months before the first administration of study drug or intention to donate blood or blood products during the study
• Received an experimental drug or used an experimental medical device within 1 month or within a period less than 10 times the drug's half-life, whichever is longer, before the first dose of the study drug is scheduled
• Positive test for human immunodeficiency virus 1 and 2 antibodies, hepatitis B surface antigen, hepatitis B core antibody or hepatitis C antibodies
• Preplanned surgery or procedures that would interfere with the conduct of the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Abiraterone acetate + pioglitazone HCl; Participants will receive 15 mg pioglitazone on Day 1 (Period 1). On Day 8 (Period 2), participants will receive 1000 mg abiraterone acetate followed by 15 mg of pioglitazone one hour later.	Drug: Pioglitazone HCl; 15 mg tablet administered by mouth on Day 1, and Day 8 1 hour after study drug administration; Drug: Abiraterone acetate; 1000 mg tablets administered by mouth on Day 8

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum observed plasma concentration of pioglitazone	Day 1 and Day 8 predose, and postdose at 30 min, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h, 36 h, 48 h, 72 h
Time to reach the maximum observed plasma concentration of pioglitazone	Day 1 and Day 8 predose, and postdose at 30 min, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h, 36 h, 48 h, 72 h
Area under the plasma concentration-time curve from time 0 to time of the last observed quantifiable concentration of pioglitazone	Day 1 and Day 8 predose, and postdose at 30 min, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h, 36 h, 48 h, 72 h
Area under the plasma concentration-time curve from time 0 to infinite time of pioglitazone	Day 1 and Day 8 predose, and postdose at 30 min, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h, 36 h, 48 h, 72 h
Percentage of area under the plasma concentration time curve obtained by extrapolation of pioglitazone	Day 1 and Day 8 predose, and postdose at 30 min, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h, 36 h, 48 h, 72 h
Elimination half-life associated with the terminal slope of the semilogarithmic drug concentration-time curve of pioglitazone	Day 1 and Day 8 predose, and postdose at 30 min, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h, 36 h, 48 h, 72 h
Time to last observed quantifiable plasma concentration of pioglitazone	Day 1 and Day 8 predose, and postdose at 30 min, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h, 36 h, 48 h, 72 h

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of participants affected by adverse events by MedDRA system organ class (SOC) and Preferred term (PT)	Up to 30 days after the last dose of study medication
Maximum observed plasma concentration of abiraterone	Day 8 predose, and postdose at 30 min, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h, 36 h, 48 h, 72 h
Time to reach the maximum observed plasma concentration of abiraterone	Day 8 predose, and postdose at 30 min, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h, 36 h, 48 h, 72 h
Area under the plasma concentration-time curve from time 0 to time of the last observed quantifiable concentration of abiraterone	Day 8 predose, and postdose at 30 min, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h, 36 h, 48 h, 72 h
Area under the plasma concentration-time curve from time 0 to infinite time of abiraterone	Day 8 predose, and postdose at 30 min, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h, 36 h, 48 h, 72 h
Percentage of area under the plasma concentration-time curve obtained by extrapolation of abiraterone	Day 8 predose, and postdose at 30 min, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h, 36 h, 48 h, 72 h
Elimination half-life associated with the terminal slope of the semilogarithmic drug concentration-time curve of abiraterone	Day 8 predose, and postdose at 30 min, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h, 36 h, 48 h, 72 h
Time to last observed quantifiable plasma concentration of abiraterone	Day 8 predose, and postdose at 30 min, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h, 36 h, 48 h, 72 h
Apparent total plasma clearance of drug after extravascular administration of pioglitazone	Day 8 predose, and postdose at 30 min, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h, 36 h, 48 h, 72 h
Metabolite to parent drug ratio for maximum observed plasma concentration	Day 1 and Day 8 predose, and postdose at 30 min, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h, 36 h, 48 h, 72 h
Metabolite to parent drug ratio for area under the plasma concentration time curve from time 0 to time of the last observed quantifiable concentration	Day 1 and Day 8 predose, and postdose at 30 min, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h, 36 h, 48 h, 72 h
Metabolite to parent drug ratio for area under the plasma concentration time curve from time 0 to infinite time	Day 1 and Day 8 predose, and postdose at 30 min, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h, 36 h, 48 h, 72 h

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC

Study record dates

Study Major Dates

• Study Start: May 1, 2013
• Primary Completion (Actual): July 1, 2013
• Study Completion (Actual): July 1, 2013

Study Registration Dates

• First Submitted: June 5, 2013
• First Submitted That Met QC Criteria: June 5, 2013
• First Posted (Estimate): June 7, 2013

Study Record Updates

• Last Update Posted (Estimate): April 17, 2014
• Last Update Submitted That Met QC Criteria: April 16, 2014
• Last Verified: April 1, 2014

More Information

Terms related to this study

• Keywords: Healthy volunteers; Pharmacokinetics; Abiraterone acetate; Abiraterone; Drug-drug Interaction; JNJ-589485; JNJ-212082; Pioglitazone HCl
• Additional Relevant MeSH Terms: Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Steroid Synthesis Inhibitors; Pioglitazone; Abiraterone Acetate
• Other Study ID Numbers: CR101970; 212082PCR1011 (Other Identifier: Janssen Research & Development, LLC); 2013-001408-12 (EudraCT Number)