A Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of JNJ-42721458 in Healthy Male Participants

A Randomized, Double-Blind, Placebo-Controlled Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single- and Multiple-Doses of JNJ-42721458 in Healthy Male Subjects

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (what the body does to the medication), potential immunogenicity (ability to induce an immune response), and pharmacodynamics (what the drug does to the body) after administration of JNJ-42721458 in healthy adult male participants.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: JNJ-42721458 (single dose); Drug: Placebo (single dose); Drug: JNJ-42721458 (multiple doses); Drug: Placebo (multiple doses)

Detailed Description

This is a randomized (the study medication is assigned by chance), double-blind (neither physician nor participant knows the identity of the assigned treatment), placebo-controlled (an inactive substance that is compared with a medication to test whether the medication has a real effect in a clinical study), single-ascending (increasing) dose and multiple-ascending dose study of JNJ-42721458 compound in healthy males. The study is divided in two parts. Part 1 is a single-ascending dose (SAD) study which will include up to 10 panels (using ascending doses starting from 0.1 mg) in which a single dose of the study medication will be administered on Day 1. Part 2 is a multiple-ascending dose (MAD) study which will include approximately 6 panels (using ascending doses starting from 5.0 mg) in which multiple doses of study medication will be administered once daily for 10 days.

Part 2 will be initiated after completion of dosing and all relevant evaluations from Part 1. In each panel of Part 1 and 2, 6 participants will be randomly assigned to receive JNJ-42721458 and 2 participants randomly assigned to placebo. Safety evaluations will include assessment of adverse events, physical examinations, laboratory tests, vital signs, electrocardiograms, cardiac telemetry and evaluation of injection sites which will be monitored throughout the study. The total study duration for each participant will be approximately 6-7 weeks in Part 1 and 7-8 weeks for each participant in Part 2.

• Study Type: Interventional
• Enrollment (Actual): 108
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Merksem, Belgium

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 53 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Body mass index (weight kg/m2) between 18 and 30 kg/m2, and body weight not less than 50 kg
• Participant is judged to be generally in good health based on medical history, physical examination, vital signs and laboratory safety tests
• Blood pressure between 90 and 135 mmHg systolic, inclusive, and no higher than 90 mmHg diastolic
• A 12-lead electrocardiogram consistent with normal cardiac conduction and function

Exclusion Criteria:

• History of or current clinically significant medical illness
• Clinically significant abnormal values for hematology, clinical chemistry or urinalysis at screening or on Day -1 (at admission to the study center)
• Estimated creatinine clearance of less than or equal to 80 mL/min
• Clinically significant abnormal physical examination, vital signs or 12 lead electrocardiogram at screening or on Day -1
• Participant demonstrates orthostatic change in vital signs measurements on screening or predose while going from a semi recumbent to standing position
• History of significant multiple and/or severe allergies (including latex allergies) or known history of clinically significant allergies to polyethylene glycol (PEG) containing or other PEGylated products

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

18

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: Panel 1 (0.1 mg JNJ-42721458); 6 participants will receive a single dose of 0.1 mg of JNJ-42721458.	Drug: JNJ-42721458 (single dose); JNJ-42721458 will be administered subcutaneously (an injection under the skin) as single doses, starting from 0.1 mg.
Experimental: Part 1: Panel 2 (0.3 mg JNJ-42721458); 6 participants will receive a single dose of 0.3 mg of JNJ-42721458.	Drug: JNJ-42721458 (single dose); JNJ-42721458 will be administered subcutaneously (an injection under the skin) as single doses, starting from 0.1 mg.
Experimental: Part 1: Panel 3 (1.0 mg JNJ-42721458); 6 participants will receive a single dose of 1.0 mg of JNJ-42721458.	Drug: JNJ-42721458 (single dose); JNJ-42721458 will be administered subcutaneously (an injection under the skin) as single doses, starting from 0.1 mg.
Experimental: Part 1: Panel 4 (2.5 mg JNJ-42721458); 6 participants will receive a single dose of 2.5 mg of JNJ-42721458.	Drug: JNJ-42721458 (single dose); JNJ-42721458 will be administered subcutaneously (an injection under the skin) as single doses, starting from 0.1 mg.
Experimental: Part 1: Panel 5 (5.0 mg JNJ-42721458); 6 participants will receive a single dose of 5.0 mg of JNJ-42721458.	Drug: JNJ-42721458 (single dose); JNJ-42721458 will be administered subcutaneously (an injection under the skin) as single doses, starting from 0.1 mg.
Experimental: Part 1: Panel 6 (10.0 mg JNJ-42721458); 6 participants will receive a single dose of 10.0 mg of JNJ-42721458.	Drug: JNJ-42721458 (single dose); JNJ-42721458 will be administered subcutaneously (an injection under the skin) as single doses, starting from 0.1 mg.
Experimental: Part 1: Panel 7 (20.0 mg JNJ-42721458); 6 participants will receive a single dose of 20.0 mg of JNJ-42721458.	Drug: JNJ-42721458 (single dose); JNJ-42721458 will be administered subcutaneously (an injection under the skin) as single doses, starting from 0.1 mg.
Experimental: Part 1: Panel 8; 6 participants will receive a single dose JNJ-42721458, the dose will be determined after completion of panels 1-7 in Part 1.	Drug: JNJ-42721458 (single dose); JNJ-42721458 will be administered subcutaneously (an injection under the skin) as single doses, starting from 0.1 mg.
Experimental: Part 1: Panel 9; 6 participants will receive a single dose JNJ-42721458, the dose will be determined after completion of panels 1-8 in Part 1.	Drug: JNJ-42721458 (single dose); JNJ-42721458 will be administered subcutaneously (an injection under the skin) as single doses, starting from 0.1 mg.
Experimental: Part 1: Panel 10; 6 participants will receive a single dose JNJ-42721458, the dose will be determined after completion of panels 1-9 in Part 1.	Drug: JNJ-42721458 (single dose); JNJ-42721458 will be administered subcutaneously (an injection under the skin) as single doses, starting from 0.1 mg.
Placebo Comparator: Part 1: Placebo; 2 participants from each panel will receive a single dose of placebo.	Drug: Placebo (single dose); Matching placebo will be administered subcutaneously (an injection under the skin) as a single dose in Part 1.
Experimental: Part 2: Panel 1 (5.0 mg JNJ-42721458); 6 participants will receive multiple doses of 5.0 mg of JNJ-42721458.	Drug: JNJ-42721458 (multiple doses); JNJ-42721458 will be administered subcutaneously (an injection under the skin) once daily, starting with a dose of 5.0 mg.
Experimental: Part 2: Panel 2 (10.0 mg JNJ-42721458); 6 participants will receive multiple doses of 10.0 mg of JNJ-42721458.	Drug: JNJ-42721458 (multiple doses); JNJ-42721458 will be administered subcutaneously (an injection under the skin) once daily, starting with a dose of 5.0 mg.
Experimental: Part 2: Panel 3; 6 participants will receive multiple doses of JNJ-42721458, the dose will be determined after completion of panels 1-2 in Part 2.	Drug: JNJ-42721458 (multiple doses); JNJ-42721458 will be administered subcutaneously (an injection under the skin) once daily, starting with a dose of 5.0 mg.
Experimental: Part 2: Panel 4; 6 participants will receive multiple doses of JNJ-42721458, the dose will be determined after completion of panels 1-3 in Part 2.	Drug: JNJ-42721458 (multiple doses); JNJ-42721458 will be administered subcutaneously (an injection under the skin) once daily, starting with a dose of 5.0 mg.
Experimental: Part 2: Panel 5; 6 participants will receive multiple doses of JNJ-42721458, the dose will be determined after completion of panels 1-4 in Part 2.	Drug: JNJ-42721458 (multiple doses); JNJ-42721458 will be administered subcutaneously (an injection under the skin) once daily, starting with a dose of 5.0 mg.
Experimental: Part 2: Panel 6; 6 participants will receive multiple doses of JNJ-42721458, the dose will be determined after completion of panels 1-5 in Part 2.	Drug: JNJ-42721458 (multiple doses); JNJ-42721458 will be administered subcutaneously (an injection under the skin) once daily, starting with a dose of 5.0 mg.
Placebo Comparator: Part 2: Placebo; 2 participants from each panel will receive multiple doses of placebo.	Drug: Placebo (multiple doses); Matching placebo will be administered subcutaneously (an injection under the skin) once daily for 10 days in Part 2.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1 and 2: Number of participants with adverse events	Number of participants with adverse events will be used as a measure of safety and tolerability.	Up to 17 weeks
Part 1 and 2: Maximum observed concentration (Cmax) of JNJ-42721458		Up to Day 10 (for Part 1) and Day 27 (for Part 2)
Part 1 and 2: Time to reach the maximum plasma concentration (tmax) of JNJ-42721458		Up to Day 10 (for Part 1) and Day 27 (for Part 2)
Part 1 and 2: Area under the concentration-time curve of JNJ-42721458, from time 0 to infinity, with extrapolation of the terminal phase		Up to Day 10 (for Part 1) and Day 27 (for Part 2)
Part 1 and 2: Area under the concentration-time curve of JNJ-42721458 during a dosing interval at steady state		Up to Day 10 (for Part 1) and Day 27 (for Part 2)
Part 1 and 2: Terminal half-life (t1/2) of JNJ-42721458		Up to Day 10 (for Part 1) and Day 27 (for Part 2)
Part 1 and 2: Apparent systemic clearance of drug after subcutaneous administration of JNJ-42721458		Up to Day 10 (for Part 1) and Day 27 (for Part 2)
Part 1 and 2: Apparent volume of distribution after subcutaneous administration of JNJ-42721458		Up to Day 10 (for Part 1) and Day 27 (for Part 2)
Part 1 and 2: Plasma levels of antibodies to JNJ-42721458 for evaluation of potential immunogenicity		Up to Day 10 (for Part 1) and Day 27 (for Part 2)

Secondary Outcome Measures

Outcome Measure	Time Frame
Part 1 and 2: Change from baseline in resting heart rate	Up to Day 10 (for Part 1) and Day 27 (for Part 2)
Part 1 and 2: Change from baseline in resting peripheral blood pressure	Up to Day 10 (for Part 1) and Day 27 (for Part 2)

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC

Study record dates

Study Major Dates

• Study Start: April 1, 2013
• Primary Completion (Actual): April 1, 2014
• Study Completion (Actual): April 1, 2014

Study Registration Dates

• First Submitted: April 23, 2013
• First Submitted That Met QC Criteria: April 23, 2013
• First Posted (Estimate): April 25, 2013

Study Record Updates

• Last Update Posted (Estimate): May 6, 2014
• Last Update Submitted That Met QC Criteria: May 5, 2014
• Last Verified: May 1, 2014

More Information

Terms related to this study

• Keywords: Safety; Healthy; Pharmacokinetics; Immunogenicity; Male; Tolerability; Pharmacodynamics; JNJ-42721458
• Other Study ID Numbers: CR101337; 42721458EDI1001 (Other Identifier: Janssen Research & Development, LLC); 2013-000557-47 (EudraCT Number)