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.

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.

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