- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03058419
A Study to Evaluate the Effect of Oral Doses of JNJ-54175446 on the Inhibition of Cytochrome P450 CYP3A4, CYP2C9, CYP1A2 and CYP2D6 Activity and the Induction of CYP2B6 and CYP2C19 Activity Using a Multiple Probe Substrate Cocktail in Healthy Subjects
June 7, 2017 updated by: Janssen Research & Development, LLC
An Open-label Drug Interaction Study in Healthy Subjects to Evaluate the Effect of Oral Doses of JNJ-54175446 on the Inhibition of Cytochrome P450 CYP3A4, CYP2C9, CYP1A2 and CYP2D6 Activity and the Induction of CYP2B6 and CYP2C19 Activity Using a Multiple Probe Substrate Cocktail
The main purpose of this study is to determine the potential inhibitory/inducing effects of JNJ-54175446 after single and repeated dosing on the single-dose pharmacokinetics (PK) of a cocktail, containing selective probes of cytochrome P450 (CYP) enzymes (CYP3A4/A5, CYP2C9, CYP1A2, CYP2D6, CYP2B6, and CYP2C19) in healthy adult subjects.
Study Overview
Status
Completed
Conditions
Study Type
Interventional
Enrollment (Actual)
16
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Merksem, Belgium, 2170
- Clinical Pharmacology Unit
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 60 years (Adult)
Accepts Healthy Volunteers
Yes
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Subject must have a body mass index (BMI) between 18.0 and 30.0 kilogram per meter square (kg/m^2), inclusive (BMI = weight/height^2)
- Subject must be healthy on the basis of physical examination, medical history, vital signs, and triplicate 12-lead electrocardiograms (ECGs), including QTc according to Fridericia's formula (QTcF) less than or equal to (</=) 450 milliseconds (ms) for males and </= 470 ms for females, performed at screening and first admission to the study site
- Subject must be healthy on the basis of clinical laboratory tests performed at screening and Day -1. If the results of the hematology, serology, serum chemistry (excluding liver function tests, which must be in normal range of 1.25 * upper limit of normal laboratory range), and coagulation panel, or urinalysis are outside the normal reference ranges, the subject may be included only if the investigator judges the abnormalities to be not clinically significant
- During the study and for a minimum of 1 spermatogenesis cycle (defined as approximately 90 days) after receiving the last dose of study drug, a male subject: Who is sexually active with a woman of childbearing potential and has not had vasectomy must agree to use a barrier method of contraception (eg, condom with spermicidal foam/gel/film/cream/suppository or partner with occlusive cap [diaphragm or cervical/vault caps] with spermicidal foam/gel/film/cream/suppository). In addition, their female partner should also use a highly effective method of birth control (example, hormonal contraception) for at least the same duration. Who is sexually active with a woman who is pregnant must use a condom and Must agree not to donate sperm
- A female subject must be of non-childbearing potential at screening
Exclusion Criteria:
- Subject has a history of or current liver or renal insufficiency (estimated creatinine clearance below 60 milliliter per minute (mL/min), significant skin disease such as, but not limited to, dermatitis, eczema, Stevens-Johnson Syndrome, drug rash, psoriasis or urticaria, significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic (including coagulation disorders), rheumatologic, psychiatric, or metabolic disturbances, any inflammatory illness or any other illness that the investigator considers should exclude the subject
- Subject has a history of hepatitis B surface antigen (HBsAg) or hepatitis C antibody (anti-HCV) positive, or other clinically active liver disease, or tests positive for HBsAg or anti-HCV at screening
- Subject has a history of human immunodeficiency virus (HIV) antibody positive, or tests positive for HIV at screening
- Subject has a history of malignancy within 5 years before screening (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy that, in the opinion of the investigator, with written concurrence with the sponsor's medical monitor, is considered cured with minimal risk of recurrence)
- Subject has a history of drug or alcohol use disorder according to Diagnostic and Statistical Manual of Mental Disorders (DSM-V) criteria within 6 months before screening
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Drug Cocktail + JNJ-54175446
All subjects will receive a single dose of drug cocktail (consisting of midazolam [2 milligram (mg)], warfarin [10 mg], caffeine [50 mg], dextromethorphan [30 mg], bupropion [150 mg] and omeprazole [20 mg]) on Day 1, 7 and 11; JNJ-54175446 150 mg on Day 7, 9, 10 and 11 and JNJ-54175446 600 mg on Day 8.
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Subjects will receive JNJ-54175446 150 mg capsules orally (1*100 mg + 1*50 mg) under fasted conditions on Day 7, 9, 10 and 11.
Subjects will receive JNJ-54175446 600 mg (6*100 mg capsules) orally on Day 8.
Subjects will receive midazolam 2 mg oral emulsion [2 (milligram per milliliter (mg/mL)] as a drug cocktail on Day 1, 7 and 11.
Subjects will receive warfarin 10 mg tablets (2*5 mg) orally as a drug cocktail on Day 1, 7 and 11.
Subjects will receive caffeine 50 mg tablet (1*50 mg) orally as a drug cocktail on Day 1, 7 and 11.
Subjects will receive dextromethorphan 30 mg capsule (1*30 mg) orally as a drug cocktail on Day 1, 7 and 11.
Subjects will receive Bupropion 150 mg tablet (1*150 mg) orally as a drug cocktail on Day 1, 7 and 11.
Subjects will receive omeprazole 20 mg capsule (1*20 mg) orally as a drug cocktail on Day 1, 7 and 11.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Maximum Observed Plasma Concentration (Cmax)
Time Frame: Up to Day 17
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The Cmax is the maximum observed plasma concentration.
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Up to Day 17
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Plasma Trough Concentration (Ctrough)
Time Frame: Up to Day 17
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Ctrough is defined as observed plasma concentration of drug just prior to the beginning or at the end of a dosing interval.
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Up to Day 17
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Time to Reach Maximum Observed Plasma Concentration (Tmax)
Time Frame: Up to Day 17
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The Tmax is defined as actual sampling time to reach maximum observed concentration.
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Up to Day 17
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Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC [0-Last])
Time Frame: Up to Day 17
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The AUClast is the area under the plasma concentration-time curve from time zero to the time of the last measurable (non-below quantification limit) concentration.
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Up to Day 17
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Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC [0-infinity])
Time Frame: Up to Day 17
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The AUC (0-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, C(last) is the last observed quantifiable concentration, and lambda(z) is elimination rate constant.
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Up to Day 17
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Elimination Rate Constant (Lambda [z])
Time Frame: Up to Day 17
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Lambda (z) is first-order elimination 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.
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Up to Day 17
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Elimination Half-Life (t1/2)
Time Frame: Up to Day 17
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The elimination half-life (t1/2) is the time measured for the plasma concentration to decrease by 1 half to its original concentration.
It is associated with the terminal slope of the semi logarithmic drug concentration-time curve, and is calculated as 0.693/lambda(z).
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Up to Day 17
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Apparent Total Clearance (CL/F)
Time Frame: Up to Day 17
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Apparent total clearance is calculated as dose/AUC(0-infinity).
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Up to Day 17
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Apparent Volume of Distribution (Vd/F)
Time Frame: Up to Day 17
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Apparent volume of distribution, calculated as dose/(lambda[z]*AUC[0-infinity]).
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Up to Day 17
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Parent to Metabolite Ratio (Cmax)
Time Frame: Up to Day 17
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Parent to metabolite ratio Cmax is defined as the ratio of individual Cmax values between parent and metabolite.
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Up to Day 17
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Parent to Metabolite Ratio (AUC [Last])
Time Frame: Up to Day 17
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Parent to metabolite ratio (AUC [Last]) is defined as ratio of individual (AUC [Last]) values between parent and metabolite.
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Up to Day 17
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Parent to Metabolite Ratio (AUC [infinity])
Time Frame: Up to Day 17
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Parent to Metabolite Ratio (AUC [infinity]) is defined as the ratio of individual (AUC [infinity]) values between parent and metabolite.
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Up to Day 17
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Subjects With Adverse Events (AEs) as a Measure of Safety and Tolerability
Time Frame: Up to follow up (14 to 21 days after last dose)
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Safety and Tolerability
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Up to follow up (14 to 21 days after last dose)
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
March 14, 2017
Primary Completion (Actual)
May 15, 2017
Study Completion (Actual)
May 15, 2017
Study Registration Dates
First Submitted
February 16, 2017
First Submitted That Met QC Criteria
February 16, 2017
First Posted (Actual)
February 20, 2017
Study Record Updates
Last Update Posted (Actual)
June 8, 2017
Last Update Submitted That Met QC Criteria
June 7, 2017
Last Verified
June 1, 2017
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Central Nervous System Depressants
- Enzyme Inhibitors
- Anesthetics, Intravenous
- Anesthetics, General
- Anesthetics
- Excitatory Amino Acid Antagonists
- Excitatory Amino Acid Agents
- Purinergic Antagonists
- Purinergic Agents
- Gastrointestinal Agents
- Tranquilizing Agents
- Psychotropic Drugs
- Neurotransmitter Uptake Inhibitors
- Membrane Transport Modulators
- Antidepressive Agents
- Dopamine Agents
- Hypnotics and Sedatives
- Adjuvants, Anesthesia
- Anti-Anxiety Agents
- GABA Modulators
- GABA Agents
- Cytochrome P-450 Enzyme Inhibitors
- Antidepressive Agents, Second-Generation
- Cytochrome P-450 CYP2D6 Inhibitors
- Respiratory System Agents
- Anticoagulants
- Anti-Ulcer Agents
- Proton Pump Inhibitors
- Dopamine Uptake Inhibitors
- Phosphodiesterase Inhibitors
- Purinergic P1 Receptor Antagonists
- Central Nervous System Stimulants
- Antitussive Agents
- Midazolam
- Bupropion
- Dextromethorphan
- Warfarin
- Caffeine
- Omeprazole
Other Study ID Numbers
- CR108283
- 2016-004167-39 (EudraCT Number)
- 54175446EDI1006 (Other Identifier: Janssen Research & Development, LLC)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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