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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

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified February 2017 by Janssen Research & Development, LLC
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT03058419
First received: February 16, 2017
Last updated: NA
Last verified: February 2017
History: No changes posted
  Purpose
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.

Condition Intervention Phase
Healthy
Drug: JNJ-54175446 150 mg
Drug: JNJ-54175446 600 mg
Drug: Midazolam 2 mg
Drug: Warfarin 10 mg
Drug: Caffeine 50 mg
Drug: Dextromethorphan 30 mg
Drug: Bupropion 150 mg
Drug: Omeprazole 20 mg
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: 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

Further study details as provided by Janssen Research & Development, LLC:

Primary Outcome Measures:
  • Maximum Observed Plasma Concentration (Cmax) [ Time Frame: Up to Day 17 ]
    The Cmax is the maximum observed plasma concentration.

  • Plasma Trough Concentration (Ctrough) [ Time Frame: Up to Day 17 ]
    Ctrough is defined as observed plasma concentration of drug just prior to the beginning or at the end of a dosing interval.

  • Time to Reach Maximum Observed Plasma Concentration (Tmax) [ Time Frame: Up to Day 17 ]
    The Tmax is defined as actual sampling time to reach maximum observed concentration.

  • Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC [0-Last]) [ Time Frame: Up to Day 17 ]
    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.

  • Area Under the Plasma Concentration-Time Curve From Time Zero to Infinite Time (AUC [0-infinity]) [ Time Frame: Up to Day 17 ]
    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.

  • Elimination Rate Constant (Lambda [z]) [ Time Frame: Up to Day 17 ]
    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.

  • Elimination Half-Life (t1/2) [ Time Frame: Up to Day 17 ]
    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).

  • Apparent Total Clearance (CL/F) [ Time Frame: Up to Day 17 ]
    Apparent total clearance is calculated as dose/AUC(0-infinity).

  • Apparent Volume of Distribution (Vd/F) [ Time Frame: Up to Day 17 ]
    Apparent volume of distribution, calculated as dose/(lambda[z]*AUC[0-infinity]).

  • Parent to Metabolite Ratio (Cmax) [ Time Frame: Up to Day 17 ]
    Parent to metabolite ratio Cmax is defined as the ratio of individual Cmax values between parent and metabolite.

  • Parent to Metabolite Ratio (AUC [Last]) [ Time Frame: Up to Day 17 ]
    Parent to metabolite ratio (AUC [Last]) is defined as ratio of individual (AUC [Last]) values between parent and metabolite.

  • Parent to Metabolite Ratio (AUC [infinity]) [ Time Frame: Up to Day 17 ]
    Parent to Metabolite Ratio (AUC [infinity]) is defined as the ratio of individual (AUC [infinity]) values between parent and metabolite.


Secondary Outcome Measures:
  • 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) ]

Estimated Enrollment: 18
Study Start Date: February 2017
Estimated Study Completion Date: May 2017
Estimated Primary Completion Date: May 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Drug Cocktail
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.
Drug: Midazolam 2 mg
Subjects will receive midazolam 2 mg oral emulsion [2 (milligram per milliliter (mg/mL)] as a drug cocktail on Day 1, 7 and 11.
Drug: Warfarin 10 mg
Subjects will receive warfarin 10 mg tablets (2*5 mg) orally as a drug cocktail on Day 1, 7 and 11.
Drug: Caffeine 50 mg
Subjects will receive caffeine 50 mg tablet (1*50 mg) orally as a drug cocktail on Day 1, 7 and 11.
Drug: Dextromethorphan 30 mg
Subjects will receive dextromethorphan 30 mg capsule (1*30 mg) orally as a drug cocktail on Day 1, 7 and 11.
Drug: Bupropion 150 mg
Subjects will receive Bupropion 150 mg tablet (1*150 mg) orally as a drug cocktail on Day 1, 7 and 11.
Drug: Omeprazole 20 mg
Subjects will receive omeprazole 20 mg capsule (1*20 mg) orally as a drug cocktail on Day 1, 7 and 11.
Experimental: JNJ-54175446 150mg+ Drug Cocktail
All subjects will receive a single dose of JNJ-54175446 (150 mg) and a single dose of drug cocktail consisting of midazolam (2 mg), warfarin (10 mg), caffeine (50 mg), dextromethorphan (30 mg), bupropion (150 mg) and omeprazole (20 mg) on Day 7.
Drug: JNJ-54175446 150 mg
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.
Drug: Midazolam 2 mg
Subjects will receive midazolam 2 mg oral emulsion [2 (milligram per milliliter (mg/mL)] as a drug cocktail on Day 1, 7 and 11.
Drug: Warfarin 10 mg
Subjects will receive warfarin 10 mg tablets (2*5 mg) orally as a drug cocktail on Day 1, 7 and 11.
Drug: Caffeine 50 mg
Subjects will receive caffeine 50 mg tablet (1*50 mg) orally as a drug cocktail on Day 1, 7 and 11.
Drug: Dextromethorphan 30 mg
Subjects will receive dextromethorphan 30 mg capsule (1*30 mg) orally as a drug cocktail on Day 1, 7 and 11.
Drug: Bupropion 150 mg
Subjects will receive Bupropion 150 mg tablet (1*150 mg) orally as a drug cocktail on Day 1, 7 and 11.
Drug: Omeprazole 20 mg
Subjects will receive omeprazole 20 mg capsule (1*20 mg) orally as a drug cocktail on Day 1, 7 and 11.
Experimental: JNJ-54175446 600 mg
All subjects will receive a single dose of JNJ-54175446 (600 mg) on Day 8.
Drug: JNJ-54175446 600 mg
Subjects will receive JNJ-54175446 600 mg (6*100 mg capsules) orally on Day 8.
Experimental: JNJ-54175446 150 mg
All subjects will receive a single dose of JNJ-54175446 (150 mg) once daily on Day 9 and 10.
Drug: JNJ-54175446 150 mg
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.
Experimental: JNJ-54175446 150 mg + Drug Cocktail
All subjects will receive a single dose of JNJ-54175446 (150 mg) and a single dose of drug cocktail consisting of midazolam (2 mg), warfarin (10 mg), caffeine (50 mg), dextromethorphan (30 mg), bupropion (150 mg) and omeprazole (20 mg) on Day 11.
Drug: JNJ-54175446 150 mg
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.
Drug: Midazolam 2 mg
Subjects will receive midazolam 2 mg oral emulsion [2 (milligram per milliliter (mg/mL)] as a drug cocktail on Day 1, 7 and 11.
Drug: Warfarin 10 mg
Subjects will receive warfarin 10 mg tablets (2*5 mg) orally as a drug cocktail on Day 1, 7 and 11.
Drug: Caffeine 50 mg
Subjects will receive caffeine 50 mg tablet (1*50 mg) orally as a drug cocktail on Day 1, 7 and 11.
Drug: Dextromethorphan 30 mg
Subjects will receive dextromethorphan 30 mg capsule (1*30 mg) orally as a drug cocktail on Day 1, 7 and 11.
Drug: Bupropion 150 mg
Subjects will receive Bupropion 150 mg tablet (1*150 mg) orally as a drug cocktail on Day 1, 7 and 11.
Drug: Omeprazole 20 mg
Subjects will receive omeprazole 20 mg capsule (1*20 mg) orally as a drug cocktail on Day 1, 7 and 11.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT03058419

Contacts
Contact: This study is not yet recruiting patients. Please check back for future recruiting sites, or email JNJ.CT@sylogent.com

Locations
Belgium
Not yet recruiting
Merksem, Belgium
Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
Study Director: Janssen Research & Development, LLC Clinical trial Janssen Research & Development, LLC
  More Information

Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT03058419     History of Changes
Other Study ID Numbers: CR108283  2016-004167-39  54175446EDI1006 
Study First Received: February 16, 2017
Last Updated: February 16, 2017

Additional relevant MeSH terms:
Warfarin
Midazolam
Dextromethorphan
Caffeine
Bupropion
Omeprazole
Anticoagulants
Adjuvants, Anesthesia
Hypnotics and Sedatives
Central Nervous System Depressants
Physiological Effects of Drugs
Anti-Anxiety Agents
Tranquilizing Agents
Psychotropic Drugs
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
GABA Modulators
GABA Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Antitussive Agents
Respiratory System Agents
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Central Nervous System Stimulants
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Purinergic P1 Receptor Antagonists
Purinergic Antagonists

ClinicalTrials.gov processed this record on February 20, 2017