Back to resultsA Study to Evaluate the Effect of Ustekinumab on Cytochrome P450 Enzyme Activities Following Induction and Maintenance Dosing in Participants With Active Crohn's Disease or Ulcerative Colitis
Primary Purpose
Crohn Disease, Ulcerative Colitis
Status
Suspended
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Ustekinumab IV Infusion
Ustekinumab SC Injection
Midazolam 2 mg
Warfarin 10 mg
Vitamin K 10 mg
Omeprazole 20 mg
Dextromethorphan 30 mg
Caffeine 100 mg
Sponsored by
About this trial
This is an interventional other trial for Crohn Disease
Eligibility Criteria
Inclusion Criteria For Crohn's Disease (CD) Participants
- Participant must have a body weight in the range of 45 to 110 kilogram (kg) inclusive and have a body mass index (BMI) of 18 to 35 kilogram per meter square (kg/m^2) inclusive
- Have had moderate to severe CD or fistulizing CD of at least 3 months duration, with colitis, ileitis, or ileocolitis, confirmed at any time in the past by histology, and/or endoscopy
For Healthy Volunteers
- Healthy on the basis of physical examination, medical history, vital signs, and 12-lead electrocardiogram (ECG) performed at screening
- Healthy on the basis of clinical laboratory tests performed at screening and Day-1
- If a woman of childbearing potential, she must have a negative serum beta-human chorionic gonadotropin (hCG) pregnancy test at screening; and a negative urine pregnancy test at Day -1
Exclusion Criteria For CD Participants
- Has complications of CD such as symptomatic strictures or stenoses, short gut syndrome, or any other manifestation that might be anticipated to require surgery in the next 3 months, could preclude the use of the Crohn's Disease Activity Index (CDAI) to assess response to therapy, would possibly confound the ability to assess the effect of treatment with ustekinumab, or would alter the absorption of the probe cocktail
- Currently has or is suspected to have an abscess. Recent cutaneous and perianal abscesses are not exclusionary if drained and adequately treated at least 3 weeks prior to baseline, or 8 weeks prior to baseline for intra-abdominal abscesses, provided that there is no anticipated need for any further surgery. Participants with active fistulas may be included if there is no anticipation of a need for surgery and there are currently no abscesses identified
For Healthy Volunteers Participants
- Has an abnormal C-reactive protein (CRP) greater than (>) 2* upper limit of normal (ULN)
- Has had major surgery (example, requiring general anesthesia) within 8 weeks before screening, or will not have fully recovered from surgery, or has surgery planned during the time the participant is in screening or is expected to participate in the study (5 weeks)
- Is pregnant, nursing, or planning a pregnancy (both men and women) during the study
Sites / Locations
- WCCT Global, LLC
- Ocean Blue Medical Research Center Inc.
- Duke University
- Ghent University Hospital
- Centre Hospitalier Universitaire de Liege Domaine Universitaire du Sart Tilman
- Az Sint-Maarten
- Clinical Pharmacology Unit
- Universitatsklinikum Bonn
- Universitatsklinikum Essen
- Universitatsklinikum Freiburg
- CTC North GmbH & Co. KG, Am Universitätsklinikum Hamburg-Eppendorf
- Clinical Research Center Hannover
- University Hospital Heidelberg
- Wythenshawe Hospital
- Royal Liverpool University Hospital
- Guy's Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Crohn's Disease or Ulcerative Colitis Participants: Ustekinumab + Probe Cocktail
Healthy Participants: Probe Cocktail
Arm Description
Participants will receive a single Intravenous (IV) infusion dose of ustekinumab (dosage to be decided based on body weight) on Day 8 and a ustekinumab 90 milligram (mg) maintenance dose via subcutaneous (SC) route on Day 64. A second optional maintenance dose may be administered on Day 120 based on participants clinical response assessed by investigator. The probe cocktail (2 milligram [mg] of midazolam, 10 mg of warfarin plus 10 mg of vitamin K, 20 mg of omeprazole, 30 mg dextromethorphan, and 100 mg of caffeine) will be administered orally on Days 1, 22, and 113.
Participants will receive the probe cocktail (2 mg of midazolam, 10 mg of warfarin plus 10 mg of vitamin K, 20 mg of omeprazole, 30 mg dextromethorphan, and 100 mg of caffeine) orally on Day 1.
Outcomes
Primary Outcome Measures
For Crohn's disease (CD) or Ulcerative Colitis (UC) Participants: Geometric Mean Ratio (Day 22/ Day 1) of the Maximum Plasma Concentration (Cmax) of Cytochrome P450 Probe Substrates (Midazolam, Omeprazole, Dextromethorphan, S-warfarin and Caffeine)
Cmax is defined as maximum observed plasma concentrations. The geometric mean ratio of Cmax will be defined as the Cmax of probe substrates on Day 22/Cmax of probe substrates on Day 1.
For CD or UC Participants: Geometric Mean Ratio (Day 113/ Day 1) of the Cmax of Cytochrome P450 Probe Substrates (Midazolam, Omeprazole, Dextromethorphan, S-warfarin and Caffeine)
Cmax is defined as maximum observed plasma concentrations. The geometric mean ratio of Cmax will be defined as the Cmax of probe substrates on Day 113/Cmax of probe substrates on Day 1.
For CD or UC Participants: Geometric Mean Ratio (Day 22/ Day 1) of the Area Under the Plasma Concentration-time Curve From 0 to Infinity (AUC [0-inf]) of Cytochrome P450 Probe Substrates (Midazolam, Omeprazole, Dextromethorphan, S-warfarin and Caffeine)
(AUC [0-inf]) is defined as area under the plasma concentration versus time curve from time 0 to infinity with extrapolation of the terminal phase. The geometric mean ratio of Cmax will be defined as the (AUC [0-inf]) of probe substrates on Day 22/(AUC [0-inf]) of probe substrates on Day 1.
For CD or UC Participants: Geometric Mean Ratio (Day 113/ Day 1) of AUC (0-inf) of Cytochrome P450 Probe Substrates (Midazolam, Omeprazole, Dextromethorphan, S-warfarin and Caffeine)
(AUC [0-inf]) is defined as area under the plasma concentration versus time curve from time 0 to infinity with extrapolation of the terminal phase. The geometric mean ratio of (AUC [0-inf]) will be defined as the (AUC [0-inf]) of probe substrates on Day 113/(AUC [0-inf]) of probe substrates on Day 1.
For CD or UC Participants: Geometric Mean Ratio (Day 22/ Day 1) of Area Under the Plasma Concentration-time Curve From 0 to Last Time (AUC [0-last]) of Cytochrome P450 Probe Substrates (Midazolam, Omeprazole, Dextromethorphan, S-warfarin and Caffeine)
(AUC [0-last]) is defined as the area under the plasma concentration-time curve from time 0 to time of the last quantifiable concentration. The geometric mean ratio of (AUC [0-last]) will be defined as the (AUC [0-last]) of probe substrates on Day 22/(AUC [0-last]) of probe substrates on Day 1.
For CD or UC Participants: Geometric Mean Ratio (Day 113/ Day 1) of AUC (0-last) of Cytochrome P450 Probe Substrates (Midazolam, Omeprazole, Dextromethorphan, S-warfarin and Caffeine)
(AUC [0-last]) is defined as the area under the plasma concentration-time curve from time 0 to time of the last quantifiable concentration. The geometric mean ratio of (AUC [0-last]) will be defined as the (AUC [0-last]) of probe substrates on Day 113/(AUC [0-last]) of probe substrates on Day 1.
For CD or UC Participants: Geometric Mean Ratio (Day 22/ Day 1) of the Area Under the Plasma Concentration-time Curve From 0 to 24 Hours (AUC [0-24]) of Cytochrome P450 Probe Substrates (Midazolam, Omeprazole, Dextromethorphan, and Caffeine)
(AUC [0-24]) is defined as area under the plasma concentration-time curve from time 0 to 24 hours. The geometric mean ratio of (AUC [0-24]) will be defined as the (AUC [0-24]) of probe substrates on Day 22/(AUC [0-24]) of probe substrates on Day 1.
For CD or UC Participants: Geometric Mean Ratio (Day 113/ Day 1) of the Area Under the Plasma Concentration-time Curve From 0 to 24 Hours (AUC [0-24]) of Cytochrome P450 Probe Substrates (Midazolam, Omeprazole, Dextromethorphan, and Caffeine)
(AUC [0-24]) is defined as area under the plasma concentration-time curve from time 0 to 24 hours. The geometric mean ratio of (AUC [0-24]) will be defined as the (AUC [0-24]) of probe substrates on Day 113/(AUC [0-24]) of probe substrates on Day 1.
For CD or UC Participants: Geometric Mean Ratio (Day 22/ Day 1) of the Area Under the Plasma Concentration-time Curve From 0 to 96 Hours (AUC [0-96]) of Cytochrome P450 Probe Substrate (S-warfarin)
(AUC [0-96]) is defined as area under the plasma concentration-time curve from time 0 to 96 hours. The geometric mean ratio of (AUC [0-96]) will be defined as the (AUC [0-96]) of probe substrates on Day 22/(AUC [0-96]) of probe substrates on Day 1.
For CD or UC Participants: Geometric Mean Ratio (Day 113/ Day 1) of the Area Under the Plasma Concentration-time Curve From 0 to 96 Hours (AUC [0-96]) of Cytochrome P450 Probe Substrate (S-warfarin)
(AUC [0-96]) is defined as area under the plasma concentration-time curve from time 0 to 96 hours. The geometric mean ratio of (AUC [0-96]) will be defined as the (AUC [0-96]) of probe substrates on Day 113/(AUC [0-96]) of probe substrates on Day 1.
Secondary Outcome Measures
CD and UC Participants: Time to Reach the Maximum Observed Plasma Concentration (Tmax) of Cytochrome P450 Probe Substrates (Midazolam, Omeprazole, Dextromethorphan, S-warfarin and Caffeine)
Tmax is defined as time to reach the maximum observed plasma concentration of Cytochrome P450 Probe Substrates.
CD and UC Participants: Terminal Half-Life (T1/2) of Cytochrome P450 Probe Substrates (Midazolam, Omeprazole, Dextromethorphan, S-warfarin and Caffeine)
T1/2 is defined as 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).
CD and UC Participants: Apparent Total Systemic Clearance (CL/F) of Cytochrome P450 Probe Substrates (Midazolam, Omeprazole, Dextromethorphan, S-warfarin and Caffeine)
CL/F after extravascular administration is defined as the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
CD and UC Participants: Apparent Volume of Distribution (Vz/F) of Cytochrome P450 Probe Substrates (Midazolam, Omeprazole, Dextromethorphan, S-warfarin and Caffeine)
Vz/F based on terminal phase after extravascular administration is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired serum concentration of a drug. Apparent volume of distribution after subcutaneous dose (Vz/F) is influenced by the fraction absorbed.
CD and UC Participants: Twelve Hour Urine Dextromethorphan to Dextrorphan Ratio
Urine samples will be analyzed to determine 12 hour urine dextromethorphan to dextrorphan ratio.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs were events between administration of study drug and up to Day 176 that were absent before treatment or that worsened relative to pre-treatment state.
Full Information
NCT ID
NCT03358706
First Posted
November 27, 2017
Last Updated
July 21, 2023
Sponsor
Janssen Research & Development, LLC
1. Study Identification
Unique Protocol Identification Number
NCT03358706
Brief Title
A Study to Evaluate the Effect of Ustekinumab on Cytochrome P450 Enzyme Activities Following Induction and Maintenance Dosing in Participants With Active Crohn's Disease or Ulcerative Colitis
Official Title
A Phase 1, Open-label, Drug Interaction Study to Evaluate the Effect of Ustekinumab on Cytochrome P450 Enzyme Activities Following Induction and Maintenance Dosing in Participants With Active Crohn's Disease or Ulcerative Colitis.
Study Type
Interventional
2. Study Status
Record Verification Date
July 2023
Overall Recruitment Status
Suspended
Why Stopped
unavailability of probe substrates
Study Start Date
February 2, 2018 (Actual)
Primary Completion Date
October 1, 2024 (Anticipated)
Study Completion Date
October 1, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Janssen Research & Development, LLC
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to evaluate the potential effects of an intravenous (IV) induction and subcutaneous (SC) maintenance administration of ustekinumab on the pharmacokinetic (PK) of a cocktail of representative probe substrates of cytochrome P450 (CYP) enzymes (CYP3A4, CYP2C9, CYP2C19, CYP2D6, and CYP1A2) in participants with Active Crohn's disease (CD) or Ulcerative Colitis (UC).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Crohn Disease, Ulcerative Colitis
7. Study Design
Primary Purpose
Other
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
57 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Crohn's Disease or Ulcerative Colitis Participants: Ustekinumab + Probe Cocktail
Arm Type
Experimental
Arm Description
Participants will receive a single Intravenous (IV) infusion dose of ustekinumab (dosage to be decided based on body weight) on Day 8 and a ustekinumab 90 milligram (mg) maintenance dose via subcutaneous (SC) route on Day 64. A second optional maintenance dose may be administered on Day 120 based on participants clinical response assessed by investigator. The probe cocktail (2 milligram [mg] of midazolam, 10 mg of warfarin plus 10 mg of vitamin K, 20 mg of omeprazole, 30 mg dextromethorphan, and 100 mg of caffeine) will be administered orally on Days 1, 22, and 113.
Arm Title
Healthy Participants: Probe Cocktail
Arm Type
Experimental
Arm Description
Participants will receive the probe cocktail (2 mg of midazolam, 10 mg of warfarin plus 10 mg of vitamin K, 20 mg of omeprazole, 30 mg dextromethorphan, and 100 mg of caffeine) orally on Day 1.
Intervention Type
Drug
Intervention Name(s)
Ustekinumab IV Infusion
Intervention Description
Participants will receive a single IV infusion dose of ustekinumab (dosage to be decided based on body weight) on Day 8.
Intervention Type
Drug
Intervention Name(s)
Ustekinumab SC Injection
Intervention Description
Participants will receive a Ustekinumab 90 mg SC maintenance dose on Day 64. A second optional maintenance dose may be administered on Day 120 based on participants clinical response assessed by investigator.
Intervention Type
Drug
Intervention Name(s)
Midazolam 2 mg
Intervention Description
Participants will receive 2 milligram per milliliter (mg/ml) syrup of midazolam as a component of the Cytochrome P 450 probe cocktail orally.
Intervention Type
Drug
Intervention Name(s)
Warfarin 10 mg
Intervention Description
Participants will receive 10 mg tablet of warfarin as a component of the Cytochrome P 450 probe cocktail orally.
Intervention Type
Drug
Intervention Name(s)
Vitamin K 10 mg
Intervention Description
Participants will receive 10 mg tablet of vitamin K as a component of the Cytochrome P 450 probe cocktail orally.
Intervention Type
Drug
Intervention Name(s)
Omeprazole 20 mg
Intervention Description
Participants will receive 20 mg capsule of omeprazole as a component of the Cytochrome P 450 probe cocktail orally.
Intervention Type
Drug
Intervention Name(s)
Dextromethorphan 30 mg
Intervention Description
Participants will receive 30 mg capsule of dextromethorphan as a component of the Cytochrome P 450 probe cocktail orally.
Intervention Type
Drug
Intervention Name(s)
Caffeine 100 mg
Intervention Description
Participants will receive 100 mg tablet of caffeine as a component of the Cytochrome P 450 probe cocktail orally.
Primary Outcome Measure Information:
Title
For Crohn's disease (CD) or Ulcerative Colitis (UC) Participants: Geometric Mean Ratio (Day 22/ Day 1) of the Maximum Plasma Concentration (Cmax) of Cytochrome P450 Probe Substrates (Midazolam, Omeprazole, Dextromethorphan, S-warfarin and Caffeine)
Description
Cmax is defined as maximum observed plasma concentrations. The geometric mean ratio of Cmax will be defined as the Cmax of probe substrates on Day 22/Cmax of probe substrates on Day 1.
Time Frame
Day 1 and 22: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post dose
Title
For CD or UC Participants: Geometric Mean Ratio (Day 113/ Day 1) of the Cmax of Cytochrome P450 Probe Substrates (Midazolam, Omeprazole, Dextromethorphan, S-warfarin and Caffeine)
Description
Cmax is defined as maximum observed plasma concentrations. The geometric mean ratio of Cmax will be defined as the Cmax of probe substrates on Day 113/Cmax of probe substrates on Day 1.
Time Frame
Day 1 and 113: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post dose
Title
For CD or UC Participants: Geometric Mean Ratio (Day 22/ Day 1) of the Area Under the Plasma Concentration-time Curve From 0 to Infinity (AUC [0-inf]) of Cytochrome P450 Probe Substrates (Midazolam, Omeprazole, Dextromethorphan, S-warfarin and Caffeine)
Description
(AUC [0-inf]) is defined as area under the plasma concentration versus time curve from time 0 to infinity with extrapolation of the terminal phase. The geometric mean ratio of Cmax will be defined as the (AUC [0-inf]) of probe substrates on Day 22/(AUC [0-inf]) of probe substrates on Day 1.
Time Frame
Day 1 and 22: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post dose
Title
For CD or UC Participants: Geometric Mean Ratio (Day 113/ Day 1) of AUC (0-inf) of Cytochrome P450 Probe Substrates (Midazolam, Omeprazole, Dextromethorphan, S-warfarin and Caffeine)
Description
(AUC [0-inf]) is defined as area under the plasma concentration versus time curve from time 0 to infinity with extrapolation of the terminal phase. The geometric mean ratio of (AUC [0-inf]) will be defined as the (AUC [0-inf]) of probe substrates on Day 113/(AUC [0-inf]) of probe substrates on Day 1.
Time Frame
Day 1 and 113: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post dose
Title
For CD or UC Participants: Geometric Mean Ratio (Day 22/ Day 1) of Area Under the Plasma Concentration-time Curve From 0 to Last Time (AUC [0-last]) of Cytochrome P450 Probe Substrates (Midazolam, Omeprazole, Dextromethorphan, S-warfarin and Caffeine)
Description
(AUC [0-last]) is defined as the area under the plasma concentration-time curve from time 0 to time of the last quantifiable concentration. The geometric mean ratio of (AUC [0-last]) will be defined as the (AUC [0-last]) of probe substrates on Day 22/(AUC [0-last]) of probe substrates on Day 1.
Time Frame
Day 1 and 22: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post dose
Title
For CD or UC Participants: Geometric Mean Ratio (Day 113/ Day 1) of AUC (0-last) of Cytochrome P450 Probe Substrates (Midazolam, Omeprazole, Dextromethorphan, S-warfarin and Caffeine)
Description
(AUC [0-last]) is defined as the area under the plasma concentration-time curve from time 0 to time of the last quantifiable concentration. The geometric mean ratio of (AUC [0-last]) will be defined as the (AUC [0-last]) of probe substrates on Day 113/(AUC [0-last]) of probe substrates on Day 1.
Time Frame
Day 1 and 113: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post dose
Title
For CD or UC Participants: Geometric Mean Ratio (Day 22/ Day 1) of the Area Under the Plasma Concentration-time Curve From 0 to 24 Hours (AUC [0-24]) of Cytochrome P450 Probe Substrates (Midazolam, Omeprazole, Dextromethorphan, and Caffeine)
Description
(AUC [0-24]) is defined as area under the plasma concentration-time curve from time 0 to 24 hours. The geometric mean ratio of (AUC [0-24]) will be defined as the (AUC [0-24]) of probe substrates on Day 22/(AUC [0-24]) of probe substrates on Day 1.
Time Frame
Day 1 and 22: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post dose
Title
For CD or UC Participants: Geometric Mean Ratio (Day 113/ Day 1) of the Area Under the Plasma Concentration-time Curve From 0 to 24 Hours (AUC [0-24]) of Cytochrome P450 Probe Substrates (Midazolam, Omeprazole, Dextromethorphan, and Caffeine)
Description
(AUC [0-24]) is defined as area under the plasma concentration-time curve from time 0 to 24 hours. The geometric mean ratio of (AUC [0-24]) will be defined as the (AUC [0-24]) of probe substrates on Day 113/(AUC [0-24]) of probe substrates on Day 1.
Time Frame
Day 1 and 113: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post dose
Title
For CD or UC Participants: Geometric Mean Ratio (Day 22/ Day 1) of the Area Under the Plasma Concentration-time Curve From 0 to 96 Hours (AUC [0-96]) of Cytochrome P450 Probe Substrate (S-warfarin)
Description
(AUC [0-96]) is defined as area under the plasma concentration-time curve from time 0 to 96 hours. The geometric mean ratio of (AUC [0-96]) will be defined as the (AUC [0-96]) of probe substrates on Day 22/(AUC [0-96]) of probe substrates on Day 1.
Time Frame
Day 1 and 22: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 and 96 hours post dose
Title
For CD or UC Participants: Geometric Mean Ratio (Day 113/ Day 1) of the Area Under the Plasma Concentration-time Curve From 0 to 96 Hours (AUC [0-96]) of Cytochrome P450 Probe Substrate (S-warfarin)
Description
(AUC [0-96]) is defined as area under the plasma concentration-time curve from time 0 to 96 hours. The geometric mean ratio of (AUC [0-96]) will be defined as the (AUC [0-96]) of probe substrates on Day 113/(AUC [0-96]) of probe substrates on Day 1.
Time Frame
Day 1 and 113: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 and 96 hours post dose
Secondary Outcome Measure Information:
Title
CD and UC Participants: Time to Reach the Maximum Observed Plasma Concentration (Tmax) of Cytochrome P450 Probe Substrates (Midazolam, Omeprazole, Dextromethorphan, S-warfarin and Caffeine)
Description
Tmax is defined as time to reach the maximum observed plasma concentration of Cytochrome P450 Probe Substrates.
Time Frame
Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 (only for dextromethorphan and S-warfarin), 72 (only for S-warfarin) and 96 hours (only for S-warfarin) on Days 1, 22, and 113 postdose administration of cytochrome P450 probe substrates
Title
CD and UC Participants: Terminal Half-Life (T1/2) of Cytochrome P450 Probe Substrates (Midazolam, Omeprazole, Dextromethorphan, S-warfarin and Caffeine)
Description
T1/2 is defined as 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).
Time Frame
Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 (only for dextromethorphan and S-warfarin), 72 (only for S-warfarin) and 96 hours (only for S-warfarin) on Days 1, 22, and 113 postdose administration of cytochrome P450 probe substrates
Title
CD and UC Participants: Apparent Total Systemic Clearance (CL/F) of Cytochrome P450 Probe Substrates (Midazolam, Omeprazole, Dextromethorphan, S-warfarin and Caffeine)
Description
CL/F after extravascular administration is defined as the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
Time Frame
Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 (only for dextromethorphan and S-warfarin), 72 (only for S-warfarin) and 96 hours (only for S-warfarin) on Days 1, 22, and 113 postdose administration of cytochrome P450 probe substrates
Title
CD and UC Participants: Apparent Volume of Distribution (Vz/F) of Cytochrome P450 Probe Substrates (Midazolam, Omeprazole, Dextromethorphan, S-warfarin and Caffeine)
Description
Vz/F based on terminal phase after extravascular administration is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired serum concentration of a drug. Apparent volume of distribution after subcutaneous dose (Vz/F) is influenced by the fraction absorbed.
Time Frame
Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 (only for dextromethorphan and S-warfarin), 72 (only for S-warfarin) and 96 hours (only for S-warfarin) on Days 1, 22, and 113 postdose administration of cytochrome P450 probe substrates
Title
CD and UC Participants: Twelve Hour Urine Dextromethorphan to Dextrorphan Ratio
Description
Urine samples will be analyzed to determine 12 hour urine dextromethorphan to dextrorphan ratio.
Time Frame
Pre-dose and for 12 hours after probe cocktail administration on Day 1, 22 and 113
Title
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Description
An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs were events between administration of study drug and up to Day 176 that were absent before treatment or that worsened relative to pre-treatment state.
Time Frame
Up to Day 176
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria For Crohn's Disease (CD) Participants
Participant must have a body weight in the range of 45 to 110 kilogram (kg) inclusive and have a body mass index (BMI) of 18 to 35 kilogram per meter square (kg/m^2) inclusive
Have had moderate to severe CD or fistulizing CD of at least 3 months duration, with colitis, ileitis, or ileocolitis, confirmed at any time in the past by histology, and/or endoscopy
For Healthy Volunteers
Healthy on the basis of physical examination, medical history, vital signs, and 12-lead electrocardiogram (ECG) performed at screening
Healthy on the basis of clinical laboratory tests performed at screening and Day-1
If a woman of childbearing potential, she must have a negative serum beta-human chorionic gonadotropin (hCG) pregnancy test at screening; and a negative urine pregnancy test at Day -1
Exclusion Criteria For CD Participants
Has complications of CD such as symptomatic strictures or stenoses, short gut syndrome, or any other manifestation that might be anticipated to require surgery in the next 3 months, could preclude the use of the Crohn's Disease Activity Index (CDAI) to assess response to therapy, would possibly confound the ability to assess the effect of treatment with ustekinumab, or would alter the absorption of the probe cocktail
Currently has or is suspected to have an abscess. Recent cutaneous and perianal abscesses are not exclusionary if drained and adequately treated at least 3 weeks prior to baseline, or 8 weeks prior to baseline for intra-abdominal abscesses, provided that there is no anticipated need for any further surgery. Participants with active fistulas may be included if there is no anticipation of a need for surgery and there are currently no abscesses identified
For Healthy Volunteers Participants
Has an abnormal C-reactive protein (CRP) greater than (>) 2* upper limit of normal (ULN)
Has had major surgery (example, requiring general anesthesia) within 8 weeks before screening, or will not have fully recovered from surgery, or has surgery planned during the time the participant is in screening or is expected to participate in the study (5 weeks)
Is pregnant, nursing, or planning a pregnancy (both men and women) during the study
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Janssen Research & Development, LLC Clinical Trial
Organizational Affiliation
Janssen Research & Development, LLC
Official's Role
Study Director
Facility Information:
Facility Name
WCCT Global, LLC
City
Cypress
State/Province
California
ZIP/Postal Code
90630
Country
United States
Facility Name
Ocean Blue Medical Research Center Inc.
City
Miami Springs
State/Province
Florida
ZIP/Postal Code
33166
Country
United States
Facility Name
Duke University
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Ghent University Hospital
City
Gent
ZIP/Postal Code
9000
Country
Belgium
Facility Name
Centre Hospitalier Universitaire de Liege Domaine Universitaire du Sart Tilman
City
Liege
ZIP/Postal Code
4000
Country
Belgium
Facility Name
Az Sint-Maarten
City
Mechelen
ZIP/Postal Code
2800
Country
Belgium
Facility Name
Clinical Pharmacology Unit
City
Merksem
ZIP/Postal Code
2170
Country
Belgium
Facility Name
Universitatsklinikum Bonn
City
Bonn
ZIP/Postal Code
53127
Country
Germany
Facility Name
Universitatsklinikum Essen
City
Essen
ZIP/Postal Code
45147
Country
Germany
Facility Name
Universitatsklinikum Freiburg
City
Freiburg
ZIP/Postal Code
79106
Country
Germany
Facility Name
CTC North GmbH & Co. KG, Am Universitätsklinikum Hamburg-Eppendorf
City
Hamburg
ZIP/Postal Code
20251
Country
Germany
Facility Name
Clinical Research Center Hannover
City
Hannover
ZIP/Postal Code
30625
Country
Germany
Facility Name
University Hospital Heidelberg
City
Heidelberg
ZIP/Postal Code
69120
Country
Germany
Facility Name
Wythenshawe Hospital
City
Greater Manchester
ZIP/Postal Code
M23 9LT
Country
United Kingdom
Facility Name
Royal Liverpool University Hospital
City
Liverpool
ZIP/Postal Code
L7 8XP
Country
United Kingdom
Facility Name
Guy's Hospital
City
London
ZIP/Postal Code
SE1 9RT
Country
United Kingdom
12. IPD Sharing Statement
Learn more about this trial
A Study to Evaluate the Effect of Ustekinumab on Cytochrome P450 Enzyme Activities Following Induction and Maintenance Dosing in Participants With Active Crohn's Disease or Ulcerative Colitis
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