Clinical trial NCT02230878: A Study to Investigate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of JNJ-42847922 in Healthy Participants
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: JNJ-42847922
Phase 1
Healthy
Placebo
Lead sponsor: Janssen-Cilag International NV
Sponsor class: INDUSTRY
First posted: 2014-09-03
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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)

Primary outcomes:
measure: Supine and Standing Systolic and Diastolic Blood Pressure (BP)
timeFrame: Baseline up to End of study (7-14 days after last dose) or Early withdrawal
measure: Supine and Standing Heart Rate
timeFrame: Baseline up to End of study (7-14 days after last dose) or Early withdrawal
measure: Tympanic Temperature
timeFrame: Baseline up to End of study (7-14 days after last dose) or Early withdrawal
measure: 12 Lead Electrocardiogram (ECG): RR, QRS, PR, QT, QTcB, QTcF Interval
timeFrame: Baseline up to End of study (7-14 days after last dose) or Early withdrawal
measure: Columbia Suicide Severity Rating Scale (C-SSRS)
timeFrame: Baseline up to End of study (7-14 days after last dose) or Early withdrawal
measure: Number of Participants with Adverse Events
timeFrame: Baseline up to End of study (7-14 days after last dose) or Early withdrawal
measure: Number of Participants With Change From Baseline in Laboratory Tests Results
timeFrame: Baseline up to End of study (7-14 days after last dose) or Early withdrawal
measure: Physical and Neurological Examination
timeFrame: Baseline up to End of study (7-14 days after last dose) or Early withdrawal
Secondary outcomes:
measure: Maximum Plasma Concentration (C[max])
timeFrame: Baseline up to End of study (7-14 days after last dose) or Early withdrawal
measure: Time to Reach the Maximum Plasma Concentration (T[max])
timeFrame: Baseline up to End of study (7-14 days after last dose) or Early withdrawal
measure: Time to Reach Last Quantifiable Plasma Concentration (T[last])
timeFrame: Baseline up to End of study (7-14 days after last dose) or Early withdrawal
measure: Area Under the Plasma Concentration-Time Curve From Time Zero to hour 24 Time (AUC [0-24])
timeFrame: Baseline up to End of study (7-14 days after last dose) or Early withdrawal
measure: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC [0-last])
timeFrame: Baseline up to End of study (7-14 days after last dose) or Early withdrawal
measure: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC [0-infinity])
timeFrame: Baseline up to End of study (7-14 days after last dose) or Early withdrawal
measure: Average Plasma Concentration at Steady-State (C[avg])
timeFrame: Baseline up to End of study (7-14 days after last dose) or Early withdrawal
measure: Trough Plasma Concentration (C[trough])
timeFrame: Baseline up to End of study (7-14 days after last dose) or Early withdrawal
measure: Total Clearance (CL/F)
timeFrame: Baseline up to End of study (7-14 days after last dose) or Early withdrawal
measure: Volume of Distribution (Vd/F)
timeFrame: Baseline up to End of study (7-14 days after last dose) or Early withdrawal
measure: Elimination Half-life Period (t1/2)
timeFrame: Baseline up to End of study (7-14 days after last dose) or Early withdrawal
measure: Terminal slope (Lambda [z])
timeFrame: Baseline up to End of study (7-14 days after last dose) or Early withdrawal
measure: Mean Residence Time (MRT)
timeFrame: Baseline up to End of study (7-14 days after last dose) or Early withdrawal
measure: Amount of Drug Excreted in Urine (Ae)
timeFrame: Baseline up to End of study (7-14 days after last dose) or Early withdrawal
measure: Amount of Drug Excreted into Urine During the 24-hour Dosing Interval (Ae[0-24])
timeFrame: Baseline up to End of study (7-14 days after last dose) or Early withdrawal
measure: Percentage of Drug Excreted in Urine (Ae%dose)
timeFrame: Baseline up to End of study (7-14 days after last dose) or Early withdrawal
measure: Renal Clearance (CL[R])
timeFrame: Baseline up to End of study (7-14 days after last dose) or Early withdrawal
Other outcomes:
measure: Assessment of Sedation
timeFrame: Baseline up to End of study (7-14 days after last dose) or Early withdrawal
measure: Bond and Lader Visual Analogue Scale (B and L VAS)
timeFrame: Baseline up to End of study (7-14 days after last dose) or Early withdrawal
measure: Addiction Research Center Inventory Questionnaire (ARCI-49)
timeFrame: Baseline up to End of study (7-14 days after last dose) or Early withdrawal
Locations:
city: Berlin
country: Germany
Study officials:
affiliation: Janssen-Cilag International NV
name: Janssen-Cilag International NV Clinical Trial
role: STUDY_DIRECTOR
References: