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
Overview
- Phase
- Phase 1
- Intervention
- JNJ-42847922 5 mg
- Conditions
- Healthy
- Sponsor
- Janssen-Cilag International NV
- Enrollment
- 40
- Primary Endpoint
- Supine and Standing Heart Rate
- Status
- Completed
- Last Updated
- 9 years ago
Overview
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.
Investigators
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)
Arms & Interventions
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.
Intervention: JNJ-42847922 5 mg
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.
Intervention: Placebo
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.
Intervention: JNJ-42847922 10 mg
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.
Intervention: Placebo
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.
Intervention: JNJ-42847922 20 mg
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.
Intervention: Placebo
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.
Intervention: JNJ-42847922 40 mg
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.
Intervention: Placebo
Outcomes
Primary Outcomes
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
Supine and Standing Systolic and Diastolic Blood Pressure (BP)
Time Frame: Baseline up to End of study (7-14 days after last dose) or Early withdrawal
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).
Number of Participants with Adverse Events
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 Change From Baseline in Laboratory Tests Results
Time Frame: Baseline up to End of study (7-14 days after last dose) or Early withdrawal
Laboratory values included Hematology, clinical chemistry and urinalysis.
Physical and Neurological Examination
Time Frame: Baseline up to End of study (7-14 days after last dose) or Early withdrawal
Physical and neurological examination will be performed.
Secondary Outcomes
- Time to Reach the Maximum Plasma Concentration (T[max])(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])(Baseline up to End of study (7-14 days after last dose) or Early withdrawal)
- Total Clearance (CL/F)(Baseline up to End of study (7-14 days after last dose) or Early withdrawal)
- Volume of Distribution (Vd/F)(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])(Baseline up to End of study (7-14 days after last dose) or Early withdrawal)
- Time to Reach Last Quantifiable Plasma Concentration (T[last])(Baseline up to End of study (7-14 days after last dose) or Early withdrawal)
- Elimination Half-life Period (t1/2)(Baseline up to End of study (7-14 days after last dose) or Early withdrawal)
- Terminal slope (Lambda [z])(Baseline up to End of study (7-14 days after last dose) or Early withdrawal)
- Maximum Plasma Concentration (C[max])(Baseline up to End of study (7-14 days after last dose) or Early withdrawal)
- Average Plasma Concentration at Steady-State (C[avg])(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])(Baseline up to End of study (7-14 days after last dose) or Early withdrawal)
- Trough Plasma Concentration (C[trough])(Baseline up to End of study (7-14 days after last dose) or Early withdrawal)
- Mean Residence Time (MRT)(Baseline up to End of study (7-14 days after last dose) or Early withdrawal)
- Amount of Drug Excreted in Urine (Ae)(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])(Baseline up to End of study (7-14 days after last dose) or Early withdrawal)
- Percentage of Drug Excreted in Urine (Ae%dose)(Baseline up to End of study (7-14 days after last dose) or Early withdrawal)
- Renal Clearance (CL[R])(Baseline up to End of study (7-14 days after last dose) or Early withdrawal)