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

Phase 1
Completed
Conditions
Healthy
Interventions
Registration Number
NCT01964651
Lead Sponsor
Janssen Research & Development, LLC
Brief Summary

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.

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
40
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Cohort B (Part 1)PlaceboHealthy male participants, 18 to 55 years of age.
Cohort C (Part 2)JNJ-42165279 100 mgHealthy female participants of nonchildbearing potential (surgically sterile or postmenopausal), 18 to 58 years of age.
Cohort D (Part 2)JNJ-42165279 100 mgHealthy elderly male or female participants, from 65 to 85 years of age.
Cohort D (Part 2)PlaceboHealthy elderly male or female participants, from 65 to 85 years of age.
Cohort A (Part 1)JNJ-42165279 50 mgHealthy male participants, 18 to 55 years of age.
Cohort B (Part 1)JNJ-42165279 30 mgHealthy male participants, 18 to 55 years of age.
Cohort A (Part 1)PlaceboHealthy male participants, 18 to 55 years of age.
Cohort C (Part 2)PlaceboHealthy female participants of nonchildbearing potential (surgically sterile or postmenopausal), 18 to 58 years of age.
Primary Outcome Measures
NameTimeMethod
Plasma concentrations of JNJ-421652792 weeks
Urine concentrations of JNJ-421652792 weeks
Concentrations in cerebrospinal fluid of JNJ-421652792 weeks
The number of participants with adserve events as a measure of safety and tolerabilityApproximately 8 weeks
Secondary Outcome Measures
NameTimeMethod
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 palmitoylethanolamide2 weeks
Plasma concentrations of oleoylethanolamide2 weeks
Serum concentrations of prolactin10 days
Saliva concentrations of cortisol10 days
Concentrations in cerebrospinal fluid of N-arachidonoylethanolamine (anandamide) or its metabolites9 days
Concentrations in cerebrospinal fluid of palmitoylethanolamide or its metabolites9 days
Concentrations in cerebrospinal fluid of oleoylethanolamide or its metabolites9 days
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