Safety, Tolerability and Pharmacodynamic Activity of JNJ-26528398 in Healthy Male Participants

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the anti-inflammatory properties of JNJ-26528398 using an intravenous (IV) endotoxin-induced model of acute, transient inflammation.

Detailed Description
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This is a 2-part, single center, double-blind study (neither physician nor participant knows the treatment that the participant receives). Part 1 is designed to evaluate the safety, tolerability, and pharmacokinetics (level of drug in the blood) of a dosing regimen of an investigational drug (JNJ-26528398) prior to its use in Part 2. In Part 1, participants will be assigned by chance to receive either 3 mg/day JNJ-26528398 (6 participants) or placebo (3 participants) for 7 consecutive days while staying in the clinic for 10 days. Placebo is an inactive substance that is compared with a drug to test whether the drug has a real effect. Part 2 is designed to evaluate the anti-inflammatory properties of JNJ-26528398 by measuring markers of inflammation in the blood after intravenous (IV) administration of a substance (endotoxin) which activates the immune system and temporarily causes flu-like symptoms. In Part 2, participants will be assigned by chance to receive up to 3 mg/day JNJ-26528398 (6 participants) or placebo (4 participants) for up to 7 consecutive days while staying in the clinic for 10 days. Endotoxin will be given on the last day of study drug administration. Participants will remain in bed for at least 6 hours after endotoxin administration and will be closely monitored by study personnel.

Official Title
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A Two-Part, Randomized, Placebo-Controlled Study to Investigate the Safety, Tolerability and Pharmacodynamic Activity of JNJ-26528398 in Healthy Male Subjects Employing the Intravenous Endotoxin-Induced Model of Acute Inflammation

Conditions
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Healthy Participants

Intervention / Treatment
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* Drug: JNJ-26528398
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Nonsmoker Be in good health on the basis of physical examination, medical history, and electrocardiogram (ECG) Must have good exercise tolerance Have a body mass index of 18-29 kg/m2, inclusive, and body weight between 60 and 85 kg, inclusive Have a history of consistent dental hygiene and dental care Must adhere to required contraception (subject and partner, if applicable) during the study and for 3 months after study Must agree to not donate sperm during the study and for 3 months after study Exclusion Criteria: Is currently enrolled in an investigational study, has recently received an investigational drug (including investigational vaccines), or has donated blood within 3 months Has had a vaccination within past 3 months Has history of significant drug or alcohol abuse within past 2 years or has a positive drug screen Blood donation within past 3 months Part 2 only: Has received endotoxin within past 3 months, or has a known allergy or history of significant adverse reaction to endotoxin or its excipients lactose and polyethylene glycol 6000

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment<br> | Drug: JNJ-26528398<br>* In Study Part 1, the participant will receive an oral solution of JNJ-26528398 3 mg once daily for 7 days. The same dosing regimen is planned for Part 2, but may be adjusted (lower dose and/or fewer dosing days) based on the data from Part 1.<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* In both Study Part 1 and Part 2, the participant will receive an oral solution of matching placebo once daily for up to 7 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The TNF-α concentrations in plasma (Part 2) |  | Days 7-8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Other markers of inflammation in blood (Part 2) |  | Days 7-8 | 
| Profile of Mood States (POMS) (Part 2) | The POMS Standard Form contains 65 items and assesses six dimensions of mood: tension-anxiety, depression-dejection, anger-hostility, vigor-activity, fatigue-inertia, and confusion-bewilderment. Each item is rated by the participant using a 5-point scale ranging from 1 (not at all) to 5 (extremely). | Days 1 and 7 | 
| Incidence of adverse events amongst participants (Parts 1 and 2) |  | Days -1 to 10 and Day 24 | 
| Area under the curve (AUC) of JNJ-26528398 (Parts 1 and 2) | Blood concentrations sampled at frequent intervals | Days 1-10 | 
| Maximum plasma concentration (Cmax) of JNJ-26528398 (Parts 1 and 2) |  | Days 1-10 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Healthy participants, Pharmacodynamic, Pharmacokinetics, Intravenous Endotoxin-Induced Model, Acute Inflammation, JNJ-26528398, Anti-inflammatory