A Safety, Tolerability and Pharmacokinetics Study of JNJ-54861911 in Healthy Japanese Male Participants

A Double-Blind, Placebo-Controlled, Randomized, Single-Ascending Dose Study to Investigate the Safety, Tolerability and Pharmacokinetics of JNJ-54861911 in Healthy Japanese Male Subjects

The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics (PK, study of the way a drug enters and leaves the blood and tissues over time) of single-ascending oral doses of JNJ-54861911 in healthy Japanese male participants.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: JNJ-54861911 (25 mg); Drug: Placebo; Drug: JNJ-54861911 (50 mg); Drug: JNJ-54861911 (100 mg)

Detailed Description

This is a single-center, randomized (study medication assigned to participants by chance), double-blind (neither Investigator nor participant knows which treatment the participant receives), placebo controlled (placebo is an inactive substance that is compared with a drug to test whether the drug has a real effect in a clinical trial), study of a single-ascending dose of JNJ-54861911 in participants between 55 to 75 years of age. The duration of study will be approximately 2 to 6 weeks per participant. The study consists of 3 periods: Screening period (28 to 2 days prior to dose administration); Double-blind Treatment period (participants will receive either a single oral dose of JNJ-54861911 or placebo as tablets under fasted conditions); and a Follow-up visit period (7 to 14 days after dose administration). All the eligible participants will be assigned to any of following 3 cohorts: Cohort A (single oral dose of JNJ-54861911, 25 milligram [mg] or placebo); Cohort B (single oral dose of JNJ-54861911, 50 mg or placebo); Cohort C (single oral dose of JNJ-54861911, 100 mg or placebo). Each cohort will include 8 participants. Participants in each cohort will be randomly assigned to receive either a single oral dose of JNJ-54861911 (n = 6) or placebo (n = 2). Blood samples will be collected pre-dose and over 96 hours (that is up to Day 5) after dosing for understanding the PK characteristics of JNJ-54861911. Participants' safety will be monitored throughout the study.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Fukuoka, Japan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Signed an informed consent document indicating they understand the purpose of and procedures required for the study, and are willing to participate in the study
• A man, who is sexually active with a woman of child-bearing potential and has not had a vasectomy, must agree to use an adequate contraception method as deemed appropriate by the investigator, and must not donate sperm during the study and for 90 days after receiving the study drug
• Body mass index between 18 and 30 kilogram (kg) per square meter
• Blood pressure (supine for 5 minutes) between 90 and 150 millimeter of mercury (mm Hg) systolic, and no higher than 90 mm Hg diastolic
• Must be healthy on the basis of physical and neurological examination, medical history, vital signs, and 12-lead electrocardiogram (ECG) performed at screening or admission (up to Day 1 predose)

Exclusion Criteria:

• History of or current liver or renal impairment, significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, psychiatric, dermatological (at the puncture site) or metabolic disturbances
• History of spontaneous, prolonged and severe bleeding of unclear origin
• History of epilepsy or fits
• History of human immunodeficiency virus (HIV) antigen/antibody positive, or tests positive for HIV at screening

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort A; Single oral dose of either JNJ-54861911, 25 milligram (mg) tablet or matched placebo tablet on Day 1.	Drug: JNJ-54861911 (25 mg); Single oral dose of JNJ-54861911, 25 mg on Day 1.; Drug: Placebo; Single oral dose of placebo matched to JNJ-54861911 on Day 1.
Experimental: Cohort B; Single oral dose of either JNJ-54861911, 50 mg (2*25 mg tablets) or matched placebo tablets on Day 1.	Drug: Placebo; Single oral dose of placebo matched to JNJ-54861911 on Day 1.; Drug: JNJ-54861911 (50 mg); Single oral dose of JNJ-54861911, 50 mg on Day 1.
Experimental: Cohort C; Single oral dose of either JNJ-54861911, 100 mg (4*25 mg tablets) or matched placebo tablets on Day 1.	Drug: Placebo; Single oral dose of placebo matched to JNJ-54861911 on Day 1.; Drug: JNJ-54861911 (100 mg); Single oral dose of JNJ-54861911, 100 mg on Day 1.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)	An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 14 days after last dose administration, that were absent before treatment or that worsened relative to pretreatment state.	Screening up to 14 days after last dose administration or early withdrawal
Maximum Plasma Concentration (Cmax)	The Cmax is the maximum observed plasma concentration.	Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96 hours post-administration of drug on Day 1
Time to Reach Maximum Concentration (Tmax)	The Tmax is time to reach the maximum observed plasma concentration.	Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96 hours post-administration of drug on Day 1
Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Time (AUC [0-last])	The AUC (0-last) is area under the plasma concentration-time curve from time zero to time of last quantifiable concentration (Clast).	Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96 hours post-administration of drug on Day 1
Apparent Clearance (CL/F)	Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.	Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96 hours post-administration of drug on Day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cerebrospinal Fluid (CSF) Amyloid-Beta Concentration	Amyloid-beta (biomarker, supposed to be a key feature in the pathogenesis of Alzheimer's disease) levels in CSF will be explored.	24 hours pre-administration of drug on Day -1, 24 hours post-administration of drug on Day 2
Plasma Amyloid-Beta Concentration	Amyloid-beta (biomarker, supposed to be a key feature in the pathogenesis of Alzheimer's disease) levels in plasma will be explored.	Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96 hours post-administration of drug on Day 1

Collaborators and Investigators

• Sponsor: Janssen Pharmaceutical K.K.

Study record dates

Study Major Dates

• Study Start: June 1, 2014
• Primary Completion (Actual): August 1, 2014
• Study Completion (Actual): August 1, 2014

Study Registration Dates

• First Submitted: July 1, 2014
• First Submitted That Met QC Criteria: July 1, 2014
• First Posted (Estimate): July 2, 2014

Study Record Updates

• Last Update Posted (Estimate): September 12, 2014
• Last Update Submitted That Met QC Criteria: September 11, 2014
• Last Verified: September 1, 2014

More Information

Terms related to this study

• Keywords: Alzheimer's disease; Healthy; JNJ-54861911
• Other Study ID Numbers: CR104614; 54861911ALZ1006 (Other Identifier: Janssen Pharmaceutical K.K., Japan)