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

Janssen-Cilag International NV40 enrolled

Overview

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.

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

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

Healthy

Interventions

JNJ-42847922 5 mgDRUG

Participants will receive 5 mg of JNJ-42847922, from Day 1 up to Day 10.

JNJ-42847922 10 mgDRUG

Participants will receive 10 mg of JNJ-42847922, from Day 1 up to Day 10.

JNJ-42847922 20 mgDRUG

Participants will receive 20 mg of JNJ-42847922, from Day 1 up to Day 10.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 55 YearsHealthy volunteers:

Medical Language ↔ Plain English

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)

Locations (1)

Unnamed facility

Berlin, Germany

Outcomes

Primary Outcomes

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).

Time frame: Baseline up to End of study (7-14 days after last dose) or Early withdrawal

Supine and Standing Heart Rate

Time frame: Baseline up to End of study (7-14 days after last dose) or Early withdrawal

Tympanic Temperature

Time frame: 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

Time frame: Baseline up to End of study (7-14 days after last dose) or Early withdrawal

Columbia Suicide Severity Rating Scale (C-SSRS)

Time frame: Baseline up to End of study (7-14 days after last dose) or Early withdrawal

Number of Participants with Adverse Events

Time frame: 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.

Time frame: 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.

Data from ClinicalTrials.gov

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Secondary Outcomes

Maximum Plasma Concentration (C[max])

The C(max) is the maximum plasma concentration which will be observed at the defined time points.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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).

Time frame: 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.

Time frame: 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\[0-∞\].

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: Baseline up to End of study (7-14 days after last dose) or Early withdrawal