Berlin, Germany
NCT Number: NCT02230878
A Study to Investigate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of JNJ-42847922 in Healthy Participants
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.
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Notify MeKey information
Conditions
Age range
18 year–55 year
Sex eligibility
All sexes
Study type
Interventional
Phase
Phase 1
Primary location
About this study
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.
Who can participate
Healthy volunteers accepted: Yes
Only the study team can determine whether someone qualifies for participation.
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)
Treatment and study plan
JNJ-42847922 5 mg
DrugParticipants will receive 5 mg of JNJ-42847922, from Day 1 up to Day 10.
JNJ-42847922 10 mg
DrugParticipants will receive 10 mg of JNJ-42847922, from Day 1 up to Day 10.
JNJ-42847922 20 mg
DrugParticipants will receive 20 mg of JNJ-42847922, from Day 1 up to Day 10.
JNJ-42847922 40 mg
DrugParticipants will receive 40 mg of JNJ-42847922, from Day 1 up to Day 10 .
Placebo
DrugParticipants will receive matching placebo from Day 1 up to Day 10.
Primary outcomes
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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).
-
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
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
-
Maximum Plasma Concentration (C[max])
Time frame: Baseline up to End of study (7-14 days after last dose) or Early withdrawal
The C(max) is the maximum plasma concentration which will be observed at the defined time points.
-
Time to Reach the Maximum Plasma Concentration (T[max])
Time frame: Baseline up to End of study (7-14 days after last dose) or Early withdrawal
The T[max] is time to reach the observed maximum plasma concentration.
-
Time to Reach Last Quantifiable Plasma Concentration (T[last])
Time frame: Baseline up to End of study (7-14 days after last dose) or Early withdrawal
The T[last] is time to reach the observed maximum plasma concentration.
-
Area Under the Plasma Concentration-Time Curve From Time Zero to hour 24 Time (AUC [0-24])
Time frame: Baseline up to End of study (7-14 days after last dose) or Early withdrawal
AUC (0-24) is the area under the plasma concentration-time curve from time 0 to 24 hours post-dose.
-
Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC [0-last])
Time frame: Baseline up to End of study (7-14 days after last dose) or Early withdrawal
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.
-
Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC [0-infinity])
Time frame: Baseline up to End of study (7-14 days after last dose) or Early withdrawal
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.
-
Average Plasma Concentration at Steady-State (C[avg])
Time frame: Baseline up to End of study (7-14 days after last dose) or Early withdrawal
C(avg) is the average plasma concentration at steady state, calculated as AUC 0-24 divided by 24
-
Trough Plasma Concentration (C[trough])
Time frame: Baseline up to End of study (7-14 days after last dose) or Early withdrawal
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.
-
Total Clearance (CL/F)
Time frame: Baseline up to End of study (7-14 days after last dose) or Early withdrawal
CL/F is the total clearance of drug after extravascular administration, uncorrected for absolute bioavailability. It is calculated as Dose divided by AUC.
-
Volume of Distribution (Vd/F)
Time frame: Baseline up to End of study (7-14 days after last dose) or Early withdrawal
Vd/F is the volume of distribution after extravascular administration, uncorrected for absolute bioavailability.
-
Elimination Half-life Period (t1/2)
Time frame: Baseline up to End of study (7-14 days after last dose) or Early withdrawal
Elimination half-life associated with the terminal slope (lambda[z]) of the semi logarithmic drug concentration-time curve, calculated as 0.693/lambda (z).
-
Terminal slope (Lambda [z])
Time frame: Baseline up to End of study (7-14 days after last dose) or Early withdrawal
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.
-
Mean Residence Time (MRT)
Time frame: Baseline up to End of study (7-14 days after last dose) or Early withdrawal
MRT is the mean residence time calculated as area under the first moment curve at infinity (AUMC[0-∞]) divided by AUC[0-∞].
-
Amount of Drug Excreted in Urine (Ae)
Time frame: Baseline up to End of study (7-14 days after last dose) or Early withdrawal
Ae is the amount of urine excreted in urine. It is calculated by multiplying the urinary volume with the urinary concentration.
-
Amount of Drug Excreted into Urine During the 24-hour Dosing Interval (Ae[0-24])
Time frame: Baseline up to End of study (7-14 days after last dose) or Early withdrawal
Ae(0-24h) is the amount of drug excreted into urine during the 24-hour dosing interval.
-
Percentage of Drug Excreted in Urine (Ae%dose)
Time frame: Baseline up to End of study (7-14 days after last dose) or Early withdrawal
Ae%dose is the percentage of drug excreted into the urine calculated as (Ae divided by dose)∗100.
-
Renal Clearance (CL[R])
Time frame: Baseline up to End of study (7-14 days after last dose) or Early withdrawal
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.
Other outcomes
-
Assessment of Sedation
Time frame: Baseline up to End of study (7-14 days after last dose) or Early withdrawal
Sedation will be assessed using a reaction time (RT) test battery, the Critical Flicker Fusion (CFF) test and body sway.
-
Bond and Lader Visual Analogue Scale (B and L VAS)
Time frame: Baseline up to End of study (7-14 days after last dose) or Early withdrawal
The B and L VAS includes 16 questions with VAS scales to rate subjective feelings.
-
Addiction Research Center Inventory Questionnaire (ARCI-49)
Time frame: Baseline up to End of study (7-14 days after last dose) or Early withdrawal
The ARCI-49 item questionnaire is developed specifically to measure subjective effects of drugs with diverse pharmacological actions.
Sponsors and collaborators
Lead sponsor
Janssen-Cilag International NV
Industry
Registry information
Official study 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
Important dates
- Study start
- 2014
- Primary completion
- 2014
- Study completion
- 2014
- First posted
- Sep 3, 2014
- Registry last updated
- Jan 24, 2017
OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.
View the official ClinicalTrials.gov record (opens in a new tab)This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.
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