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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Healthy

Intervention / Treatment
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* Drug: JNJ-42847922 5 mg
* Drug: JNJ-42847922 10 mg
* Drug: JNJ-42847922 20 mg
* Drug: JNJ-42847922 40 mg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: JNJ-42847922, 5 milligram (mg) and Placebo<br>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<br>* Participants will receive 5 mg of JNJ-42847922, from Day 1 up to Day 10.<br>Drug: Placebo<br>* Participants will receive matching placebo from Day 1 up to Day 10.<br>|
| Experimental: JNJ-42847922, 10 mg and Placebo<br>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: JNJ-42847922 10 mg<br>* Participants will receive 10 mg of JNJ-42847922, from Day 1 up to Day 10.<br>Drug: Placebo<br>* Participants will receive matching placebo from Day 1 up to Day 10.<br>|
| Experimental: JNJ-42847922, 20 mg and Placebo<br>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: JNJ-42847922 20 mg<br>* Participants will receive 20 mg of JNJ-42847922, from Day 1 up to Day 10.<br>Drug: Placebo<br>* Participants will receive matching placebo from Day 1 up to Day 10.<br>|
| Experimental: JNJ-42847922, 40 mg and Placebo<br>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: JNJ-42847922 40 mg<br>* Participants will receive 40 mg of JNJ-42847922, from Day 1 up to Day 10 .<br>Drug: Placebo<br>* Participants will receive matching placebo from Day 1 up to Day 10.<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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JNJ-42847922, Phase 1, Healthy, Placebo