Pharmacokinetics (PK) and Pharmacodynamics (PD) Study of Single and Multiple Ascending Doses of JNJ-41443532 in Healthy Male Participants

Single and Multiple Ascending Dose Study to Investigate the Safety, Tolerability, Food Effect, Pharmacokinetics, and Pharmacodynamics of JNJ-41443532 in Healthy Male Subjects

The purpose of this study is to investigate the safety, tolerability, food effect as well as the pharmacokinetics (how the drug is absorbed in the body, how it is distributed within the body and how it is removed from the body over time) and pharmacodynamics (the effects of the drug) of single and multiple ascending doses of JNJ-41443532 in healthy male participants.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Placebo; Drug: JNJ-41443532; Drug: JNJ-41443532; Drug: JNJ-41443532; Drug: JNJ-41443532; Drug: JNJ-41443532; Drug: JNJ-41443532

Detailed Description

This is a randomized (study drug assigned by chance), double-blind (neither physician nor participant knows the name of the assigned drug), placebo-controlled, single and multiple ascending dose study conducted at a single study center. The study has 4 parts. Part 1 is a randomized, double-blind, alternating panel, single ascending oral dose study. Two alternating treatment panels (A and B) each with nine healthy male participants will be studied with successively increasing dose levels. Part 2 is a randomized, open-label (all people involved know the identity of the intervention), 2-period crossover study to evaluate what the effect of administering JNJ- 41443532 with food (i.e. standard high fat breakfast meal) relative to administration in the fasted state will have on pharmacokinetics/blood levels of JNJ-41443532. Part 3 is a randomized, double-blind, single oral dose study in obese, otherwise healthy male participants. Part 4 is a double-blind, randomized, placebo-controlled multiple ascending dose study in up to 5 sequential treatment groups of healthy male participants. Safety assessments include monitoring of adverse events, and evaluation of lab results, cardiac parameters, vital signs, and physical exams. In Parts 1, 2, and 3 participants receive study medication (JNJ-41443532 or placebo) orally on Day 1 after an overnight fast of at least 10 hours; planned doses are 25 to 1500 mg. In Part 4, participants receive study medication (JNJ-41443532 or placebo) orally each day for 10 consecutive days after an overnight fast of at least 10 hours; planned doses are 100 to 1000 mg.

• Study Type: Interventional
• Enrollment (Actual): 74
• 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:

• Males, age 18 to 45 years inclusive for Part 1 and age 18 to 55 years inclusive for Parts 2, 3, and 4
• Weight = 60 kilograms and Body Mass Index (BMI) between 18.5 and 29.9 kg/m2 (inclusive)
• BMI between 30 to 39.9 kg/m2 for obese participants
• Healthy on the basis of physical examination, medical history, vital signs, electrocardiogram (ECG), and clinical laboratory tests performed at screening
• Men must agree to use a double barrier method of birth control (e.g. condom and use of spermicide with diaphragm, hormonal contraceptives or intrauterine devices by female partner) and to not donate sperm during the study and for 3 months after receiving the last dose of study drug
• Willing to adhere to the prohibitions and restrictions specified in this protocol

Exclusion Criteria:

• History of, or currently active, significant illness or medical disorders, including (but not limited to) cardiovascular disease (including cardiac arrhythmias, myocardial infarction, stroke, peripheral vascular disease), endocrine or metabolic disease (e.g. hyper/hypo-thyroidism), hematological disease (e.g. von Willebrand's disease or other bleeding disorders), respiratory disease, hepatic or gastrointestinal disease, neurological or psychiatric disease, ophthalmologic disorders (including retinal disorders or cataracts), neoplastic disease, skin disorder, or any other illness that the Investigator considers should exclude the participant
• Participants at risk for QTc prolongation (specific heart rhythm irregularity)
• Within 12 months prior to screening, has had a clinically important, serious infection (e.g. hepatitis, pneumonia, or pyelonephritis), has been hospitalized for an infection or has been treated with intravenous (IV) antibiotics for an infection
• Smoker or tobacco user within the past 3 months
• History of alcohol or drug abuse
• History of clinically significant drug and/or food allergies, including allergies or intolerance (e.g. lactose intolerance)
• Donation of 1 or more units of blood or acute loss of an equivalent amount of blood within 60 days prior to study drug administration
• Received an experimental drug or used an experimental medical device within 60 days

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 001; JNJ-41443532 25mg tablet once daily	Drug: JNJ-41443532; 25mg tablet once daily; Drug: JNJ-41443532; 250mg tablet once daily; Drug: JNJ-41443532; 1500mg once daily (with 250mg tablets); Drug: JNJ-41443532; 100mg tablet once daily; Drug: JNJ-41443532; 1000mg once daily (with 250mg tablets); Drug: JNJ-41443532; 500mg once daily (with 250mg tablets)
Experimental: 002; JNJ-41443532 100mg tablet once daily	Drug: JNJ-41443532; 25mg tablet once daily; Drug: JNJ-41443532; 250mg tablet once daily; Drug: JNJ-41443532; 1500mg once daily (with 250mg tablets); Drug: JNJ-41443532; 100mg tablet once daily; Drug: JNJ-41443532; 1000mg once daily (with 250mg tablets); Drug: JNJ-41443532; 500mg once daily (with 250mg tablets)
Experimental: 003; JNJ-41443532 250mg tablet once daily	Drug: JNJ-41443532; 25mg tablet once daily; Drug: JNJ-41443532; 250mg tablet once daily; Drug: JNJ-41443532; 1500mg once daily (with 250mg tablets); Drug: JNJ-41443532; 100mg tablet once daily; Drug: JNJ-41443532; 1000mg once daily (with 250mg tablets); Drug: JNJ-41443532; 500mg once daily (with 250mg tablets)
Experimental: 004; JNJ-41443532 500mg once daily (with 250mg tablets)	Drug: JNJ-41443532; 25mg tablet once daily; Drug: JNJ-41443532; 250mg tablet once daily; Drug: JNJ-41443532; 1500mg once daily (with 250mg tablets); Drug: JNJ-41443532; 100mg tablet once daily; Drug: JNJ-41443532; 1000mg once daily (with 250mg tablets); Drug: JNJ-41443532; 500mg once daily (with 250mg tablets)
Experimental: 005; JNJ-41443532 1000mg once daily (with 250mg tablets)	Drug: JNJ-41443532; 25mg tablet once daily; Drug: JNJ-41443532; 250mg tablet once daily; Drug: JNJ-41443532; 1500mg once daily (with 250mg tablets); Drug: JNJ-41443532; 100mg tablet once daily; Drug: JNJ-41443532; 1000mg once daily (with 250mg tablets); Drug: JNJ-41443532; 500mg once daily (with 250mg tablets)
Experimental: 006; JNJ-41443532 1500mg once daily (with 250mg tablets)	Drug: JNJ-41443532; 25mg tablet once daily; Drug: JNJ-41443532; 250mg tablet once daily; Drug: JNJ-41443532; 1500mg once daily (with 250mg tablets); Drug: JNJ-41443532; 100mg tablet once daily; Drug: JNJ-41443532; 1000mg once daily (with 250mg tablets); Drug: JNJ-41443532; 500mg once daily (with 250mg tablets)
Placebo Comparator: 007; Placebo Matching placebo	Drug: Placebo; Matching placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Determine the pharmacokinetic properties of single and multiple doses JNJ-41443532 as determined by blood level concentrations.	Part 1 - Approximately 13 weeks; Part 2 - Approximately 7 weeks; Part 3 - Approximately 6 weeks; Part 4 - Approximately 7 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Determine the safety and tolerability of JNJ-41443532 as determined by evaluation of adverse events, lab results, cardiac monitoring, vital signs, and physical exams.	Part 1 - Approximately 13 weeks; Part 2 - Approximately 7 weeks; Part 3 - Approximately 6 weeks; Part 4 - Approximately 7 weeks
To explore the relationship between JNJ-41443532 plasma concentrations and pharmacodynamic effects (concentration-effect relationships).	Part 1 - Approximately 13 weeks; Part 2 - Approximately 7 weeks; Part 3 - Approximately 6 weeks; Part 4 - Approximately 7 weeks
To explore the pharmacodynamic (PD) effects of JNJ-41443532 and to compare the differences between treatment groups	Part 1 - Approximately 13 weeks; Part 2 - Approximately 7 weeks; Part 3 - Approximately 6 weeks; Part 4 - Approximately 7 weeks

Collaborators and Investigators

• Sponsor: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Study record dates

Study Major Dates

• Study Start: February 1, 2010
• Study Completion (Actual): July 1, 2010

Study Registration Dates

• First Submitted: April 15, 2010
• First Submitted That Met QC Criteria: April 19, 2010
• First Posted (Estimate): April 20, 2010

Study Record Updates

• Last Update Posted (Estimate): April 8, 2014
• Last Update Submitted That Met QC Criteria: April 7, 2014
• Last Verified: April 1, 2014

More Information

Terms related to this study

• Keywords: Healthy; Pharmacokinetics; Healthy Volunteers; JNJ-41443532
• Other Study ID Numbers: CR017065; 41443532EDI1001 (Other Identifier: Johnson & Johnson Pharmaceutical Research and Development, L.L.C.)