Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of JNJ-42165279 in Healthy Young and Elderly Participants

A Double-Blind, Placebo-Controlled, Randomized, Multiple Dose Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of JNJ-42165279 in Healthy Young and Elderly Subjects

The purpose of this study is to assess the safety, tolerability, and pharmacokinetics of JNJ-42165279 in healthy, young and elderly, male and female participants after repeated oral dose administration.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: JNJ-42165279 50 mg; Drug: Placebo; Drug: JNJ-42165279 30 mg; Drug: JNJ-42165279 100 mg

Detailed Description

This is a double-blind (neither physician nor participant knows the treatment that the participant receives), randomized (the study drug is assigned by chance), placebo-controlled (an inactive substance is compared with a medication to test whether the medication has a real effect in a clinical study) trial that will be conducted in two parts. Thirty two (32) healthy participants are planned to be included in total, in four cohorts (groups). Participants in each cohort will receive JNJ-42165279 (n=6) or placebo (n=2) once-daily for 10 consecutive days. In Part 1, two cohorts of healthy male participants, 18 to 55 years of age, will be enrolled. Cohort A will receive 50 mg JNJ-42165279 or placebo for 10 days, and Cohort B will receive 30 mg JNJ-42165279 or placebo for 10 days. In Part 2, Cohort C will consist of 8 healthy female participants of non-childbearing potential (surgically sterile or postmenopausal), 18 to 58 years of age, who will receive 100 mg JNJ-42165279 or placebo for 10 days. Cohort D will consist of 8 healthy elderly male or female participants, from 65 to 85 years of age, who will receive 100 mg JNJ-42165279 or placebo for 10 days. The dose may be adapted before each cohort starts based on available data. The maximum dose will not exceed 100 mg once-daily. For all participants, this study will consist of an eligibility screening examination (between 28 and 3 days prior to the first dose administration), a double-blind treatment phase consisting of 2 days before dosing, 10 dosing days (Day 1 to 10), 4 days after dosing (Day 11 to 14), and a follow-up examination (within 7 to 14 days after last dose administration). The total study duration for each participant will not exceed 8 weeks.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Merksem, Belgium

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Body Mass Index (BMI) between 18 and 30 kg/m2 inclusive
• Nonsmoker
• Healthy men between 18 and 55 years, inclusive (Cohorts A and B)
• Healthy women between 18 and 58 years, inclusive (Cohort C)
• Healthy men and women between 65 and 85 years of age, inclusive (Cohort D)
• Men who are sexually active with a woman of childbearing potential and have not had a vasectomy must agree to use a barrier method of birth control during the study and for 3 months after receiving the last dose of study drug. In addition, their female partners should also use an appropriate method of birth control for at least the same duration (Cohorts A, B, and D)
• Not be of childbearing potential due to either tubal ligation or hysterectomy, or who are postmenopausal (Cohorts C and D)

Exclusion Criteria:

• Clinically significant abnormal values for hematology, clinical chemistry or urinalysis at screening or admission
• Clinically significant abnormal physical examination, vital signs or electrocardiogram at screening or admission
• History of, or current, significant medical illness including (but not limited to) cardiac disease, hematological disease, lipid abnormalities, respiratory disease, diabetes mellitus, renal or hepatic insufficiency, thyroid disease, Parkinson's disease, infection, or any other illness that the Investigator considers should exclude the participant
• History of epilepsy or fits or unexplained black-outs
• Cohorts A and B only: a contraindication for spinal puncture

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort A (Part 1); Healthy male participants, 18 to 55 years of age.	Drug: JNJ-42165279 50 mg; JNJ-42165279 50 mg orally administered once daily for 10 days.; Drug: Placebo; Matching placebo orally administered once daily for 10 days.
Experimental: Cohort B (Part 1); Healthy male participants, 18 to 55 years of age.	Drug: Placebo; Matching placebo orally administered once daily for 10 days.; Drug: JNJ-42165279 30 mg; JNJ-42165279 30 mg orally administered once daily for 10 days.
Experimental: Cohort C (Part 2); Healthy female participants of nonchildbearing potential (surgically sterile or postmenopausal), 18 to 58 years of age.	Drug: Placebo; Matching placebo orally administered once daily for 10 days.; Drug: JNJ-42165279 100 mg; JNJ-42165279 100 mg orally administered once daily for 10 days.
Experimental: Cohort D (Part 2); Healthy elderly male or female participants, from 65 to 85 years of age.	Drug: Placebo; Matching placebo orally administered once daily for 10 days.; Drug: JNJ-42165279 100 mg; JNJ-42165279 100 mg orally administered once daily for 10 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Plasma concentrations of JNJ-42165279	2 weeks
Urine concentrations of JNJ-42165279	2 weeks
Concentrations in cerebrospinal fluid of JNJ-42165279	2 weeks
The number of participants with adserve events as a measure of safety and tolerability	Approximately 8 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Enzyme fatty acid amide hydrolase inhibition, as measured in white blood cells (WBCs)	Approximately 4 weeks
Plasma concentrations of N-arachidonoylethanolamine (anandamide)	2 weeks
Plasma concentrations of palmitoylethanolamide	2 weeks
Plasma concentrations of oleoylethanolamide	2 weeks
Serum concentrations of prolactin	10 days
Saliva concentrations of cortisol	10 days
Concentrations in cerebrospinal fluid of N-arachidonoylethanolamine (anandamide) or its metabolites	9 days
Concentrations in cerebrospinal fluid of palmitoylethanolamide or its metabolites	9 days
Concentrations in cerebrospinal fluid of oleoylethanolamide or its metabolites	9 days

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC

Study record dates

Study Major Dates

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

Study Registration Dates

• First Submitted: October 14, 2013
• First Submitted That Met QC Criteria: October 14, 2013
• First Posted (Estimate): October 17, 2013

Study Record Updates

• Last Update Posted (Estimate): December 3, 2014
• Last Update Submitted That Met QC Criteria: December 2, 2014
• Last Verified: December 1, 2014

More Information

Terms related to this study

• Keywords: Elderly; Healthy; Pharmacokinetics; JNJ-42165279; Young
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; JNJ-42165279
• Other Study ID Numbers: CR102575; 42165279EDI1002 (Other Identifier: Janssen Research & Development, LLC); 2013-002309-67 (EudraCT Number)