A Study to Investigate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of JNJ-42847922 in Healthy Participants

A Randomized, Double-blind, Placebo-controlled Multiple Ascending Dose Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of JNJ-42847922 in Healthy Male and Female Subjects

The purpose of this study is to investigate the safety, tolerability, pharmacokinetic (the study of the way a drug enters and leaves the blood and tissues over time), dose-proportionality, accumulation, urinary excretion, pharmacodynamics (the study of how drugs act on the body) and sedative effects of JNJ-42847922 in healthy male and female participants.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: JNJ-42847922 5 mg; Drug: Placebo; Drug: JNJ-42847922 10 mg; Drug: JNJ-42847922 20 mg; Drug: JNJ-42847922 40 mg

Detailed Description

This is a Phase 1, double blind (a medical research study in which neither the researchers nor the participants know what treatment the participants is receiving), randomized (study drug assigned by chance), placebo controlled, multiple ascending dose study. The study will consist of 3 parts: a Screening period (Days -21 to -2), a Double-blind treatment period (Day -1 to Day 11), and a Follow-up period (within 7 to 14 days after last dose administration). In double blind treatment period, participants will be randomly assigned to 5, 10, 20, and 40 milligram (mg) or placebo. Number of participants with any clinically relevant changes (adverse events [AEs], laboratory results,electrocardiogram [ECG], Vital signs, Physical and neurological, sedation & concentration) and columbia suicide severity rating (CSSR) scale will be evaluated as primary outcome measure. Participants' safety will be monitored throughout the study.

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

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Women should not be of child bearing potential due to either tubal ligation or hysterectomy or who are postmenopausal (no spontaneous menses for at least 2 years
• Body Mass Index (BMI) between 18 and 30 kilogram per meter square (kg/m^2) inclusive (BMI=weight/height^2)
• Participants must be healthy / medically stable on the basis of clinical laboratory tests performed at screening. If the results of the serum chemistry panel, hematology, or urinalysis are outside the normal reference ranges, retesting of an abnormal lab value(s) that may lead to exclusion will be allowed once during the screening phase
• Non-smokers (not smoked for 6 months prior to screening)
• Participant must be willing and able to adhere to the prohibitions and restrictions specified in this protocol

Exclusion Criteria:

• Clinically significant abnormal values for hematology, serum chemistry or urinalysis at screening or admission
• Clinically significant abnormal physical or neurological examination, vital signs or 12-lead electrocardiogram (ECG) at screening or admission
• History of or current significant medical illness including (but not limited to) cardiac arrhythmias or other cardiac disease, hematological disease, lipid abnormalities, bronchospastic 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
• Serology positive for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibodies or human immunodeficiency virus (HIV) antibodies
• Subjects with a relevant history of a suicide attempt or suicidal behavior. Any recent suicidal ideation within the last 6 months (a level of 4 or 5), or who are at significant risk to commit suicide, as judged by the investigator using the columbia suicide severity rating score (C-SSRS)

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: JNJ-42847922, 5 milligram (mg) and Placebo; Participants will be receive either 5 mg of JNJ-42847922 from Day 1 up to Day 10 or matching placebo from Day 1 up to Day 10.	Drug: JNJ-42847922 5 mg; Participants will receive 5 mg of JNJ-42847922, from Day 1 up to Day 10.; Drug: Placebo; Participants will receive matching placebo from Day 1 up to Day 10.
Experimental: JNJ-42847922, 10 mg and Placebo; Participants will be receive either 10 mg of JNJ-42847922 from Day 1 up to Day 10 or matching placebo from Day 1 up to Day 10.	Drug: Placebo; Participants will receive matching placebo from Day 1 up to Day 10.; Drug: JNJ-42847922 10 mg; Participants will receive 10 mg of JNJ-42847922, from Day 1 up to Day 10.
Experimental: JNJ-42847922, 20 mg and Placebo; Participants will be receive either 20 mg of JNJ-42847922 from Day 1 up to Day 10 or matching placebo from Day 1 up to Day 10.	Drug: Placebo; Participants will receive matching placebo from Day 1 up to Day 10.; Drug: JNJ-42847922 20 mg; Participants will receive 20 mg of JNJ-42847922, from Day 1 up to Day 10.
Experimental: JNJ-42847922, 40 mg and Placebo; Participants will be receive either 40mg of JNJ-42847922 from Day 1 up to Day 10 or matching placebo from Day 1 up to Day 10.	Drug: Placebo; Participants will receive matching placebo from Day 1 up to Day 10.; Drug: JNJ-42847922 40 mg; Participants will receive 40 mg of JNJ-42847922, from Day 1 up to Day 10 .

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Supine and Standing Systolic and Diastolic Blood Pressure (BP)	BP is the pressure of the blood within the arteries. It is produced primarily by the contraction of the heart muscle. BP measurement is recorded by 2 numbers: systolic BP (SBP, BP when heart is contracting; it is the maximum arterial pressure during contraction of left ventricle) and diastolic BP (DBP, BP when heart is relaxing; it is the minimum arterial pressure during relaxation and dilation of ventricles).	Baseline up to End of study (7-14 days after last dose) or Early withdrawal
Supine and Standing Heart Rate		Baseline up to End of study (7-14 days after last dose) or Early withdrawal
Tympanic Temperature		Baseline up to End of study (7-14 days after last dose) or Early withdrawal
12 Lead Electrocardiogram (ECG): RR, QRS, PR, QT, QTcB, QTcF Interval		Baseline up to End of study (7-14 days after last dose) or Early withdrawal
Columbia Suicide Severity Rating Scale (C-SSRS)		Baseline up to End of study (7-14 days after last dose) or Early withdrawal
Number of Participants with Adverse Events		Baseline up to End of study (7-14 days after last dose) or Early withdrawal
Number of Participants With Change From Baseline in Laboratory Tests Results	Laboratory values included Hematology, clinical chemistry and urinalysis.	Baseline up to End of study (7-14 days after last dose) or Early withdrawal
Physical and Neurological Examination	Physical and neurological examination will be performed.	Baseline up to End of study (7-14 days after last dose) or Early withdrawal

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Plasma Concentration (C[max])	The C(max) is the maximum plasma concentration which will be observed at the defined time points.	Baseline up to End of study (7-14 days after last dose) or Early withdrawal
Time to Reach the Maximum Plasma Concentration (T[max])	The T[max] is time to reach the observed maximum plasma concentration.	Baseline up to End of study (7-14 days after last dose) or Early withdrawal
Time to Reach Last Quantifiable Plasma Concentration (T[last])	The T[last] is time to reach the observed maximum plasma concentration.	Baseline up to End of study (7-14 days after last dose) or Early withdrawal
Area Under the Plasma Concentration-Time Curve From Time Zero to hour 24 Time (AUC [0-24])	AUC (0-24) is the area under the plasma concentration-time curve from time 0 to 24 hours post-dose.	Baseline up to End of study (7-14 days after last dose) or Early withdrawal
Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC [0-last])	AUC (last) is the area under the plasma concentration-time curve from time zero time of the last quantifiable concentration C(last), and C(last) is the last observed quantifiable concentration.	Baseline up to End of study (7-14 days after last dose) or Early withdrawal
Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC [0-infinity])	AUC (infinity) is the area under the plasma concentration-time curve from time zero to infinite time, calculated as the sum of AUC(last) and C(last)/lambda(z), wherein AUC(last) is area under the plasma concentration-time curve from time zero to last quantifiable time; and C(last) is the last observed quantifiable concentration; and lambda(z) is elimination rate constant.	Baseline up to End of study (7-14 days after last dose) or Early withdrawal
Average Plasma Concentration at Steady-State (C[avg])	C(avg) is the average plasma concentration at steady state, calculated as AUC 0-24 divided by 24	Baseline up to End of study (7-14 days after last dose) or Early withdrawal
Trough Plasma Concentration (C[trough])	Trough plasma concentration is the plasma concentration before dosing or at the end of the dosing interval of any dose other than the first dose.	Baseline up to End of study (7-14 days after last dose) or Early withdrawal
Total Clearance (CL/F)	CL/F is the total clearance of drug after extravascular administration, uncorrected for absolute bioavailability. It is calculated as Dose divided by AUC.	Baseline up to End of study (7-14 days after last dose) or Early withdrawal
Volume of Distribution (Vd/F)	Vd/F is the volume of distribution after extravascular administration, uncorrected for absolute bioavailability.	Baseline up to End of study (7-14 days after last dose) or Early withdrawal
Elimination Half-life Period (t1/2)	Elimination half-life associated with the terminal slope (lambda[z]) of the semi logarithmic drug concentration-time curve, calculated as 0.693/lambda (z).	Baseline up to End of study (7-14 days after last dose) or Early withdrawal
Terminal slope (Lambda [z])	Terminal slope is defined by first-order rate constant associated with the terminal portion of the curve, determined as the negative slope of the terminal log-linear phase of the drug concentration-time curve.	Baseline up to End of study (7-14 days after last dose) or Early withdrawal
Mean Residence Time (MRT)	MRT is the mean residence time calculated as area under the first moment curve at infinity (AUMC[0-∞]) divided by AUC[0-∞].	Baseline up to End of study (7-14 days after last dose) or Early withdrawal
Amount of Drug Excreted in Urine (Ae)	Ae is the amount of urine excreted in urine. It is calculated by multiplying the urinary volume with the urinary concentration.	Baseline up to End of study (7-14 days after last dose) or Early withdrawal
Amount of Drug Excreted into Urine During the 24-hour Dosing Interval (Ae[0-24])	Ae(0-24h) is the amount of drug excreted into urine during the 24-hour dosing interval.	Baseline up to End of study (7-14 days after last dose) or Early withdrawal
Percentage of Drug Excreted in Urine (Ae%dose)	Ae%dose is the percentage of drug excreted into the urine calculated as (Ae divided by dose)∗100.	Baseline up to End of study (7-14 days after last dose) or Early withdrawal
Renal Clearance (CL[R])	CL(R) is the renal clearance of the drug, calculated as Ae/AUC[0-infinity] on Day 1 or Ae(0-24)/AUC(0-24) on Day 5 and Day 10.	Baseline up to End of study (7-14 days after last dose) or Early withdrawal

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of Sedation	Sedation will be assessed using a reaction time (RT) test battery, the Critical Flicker Fusion (CFF) test and body sway.	Baseline up to End of study (7-14 days after last dose) or Early withdrawal
Bond and Lader Visual Analogue Scale (B and L VAS)	The B and L VAS includes 16 questions with VAS scales to rate subjective feelings.	Baseline up to End of study (7-14 days after last dose) or Early withdrawal
Addiction Research Center Inventory Questionnaire (ARCI-49)	The ARCI-49 item questionnaire is developed specifically to measure subjective effects of drugs with diverse pharmacological actions.	Baseline up to End of study (7-14 days after last dose) or Early withdrawal

Collaborators and Investigators

• Sponsor: Janssen-Cilag International NV

Study record dates

Study Major Dates

• Study Start: May 1, 2014
• Primary Completion (Actual): November 1, 2014
• Study Completion (Actual): November 1, 2014

Study Registration Dates

• First Submitted: August 14, 2014
• First Submitted That Met QC Criteria: September 2, 2014
• First Posted (Estimate): September 3, 2014

Study Record Updates

• Last Update Posted (Estimate): January 24, 2017
• Last Update Submitted That Met QC Criteria: January 21, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Keywords: Healthy; Phase 1; Placebo; JNJ-42847922
• Other Study ID Numbers: CR104154; 42847922EDI1003 (Other Identifier: Janssen-Cilag International NV); 2014-000600-95 (EudraCT Number)