Crohn DiseasePhase 1NCT03358706
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
A Phase 1 study testing Ustekinumab IV Infusion, Ustekinumab SC Injection and Midazolam 2 mg in people with Crohn Disease and Ulcerative Colitis, run by Janssen Research & Development, LLC at 16 sites in 4 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Crohn Disease, Ulcerative Colitis
- What is being tested?
- Ustekinumab IV Infusion, Ustekinumab SC Injection and Midazolam 2 mg
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 28 participants
- Where
- 16 sitesin 4 countries
- Study dates
- 2 Feb 2018to 22 Nov 2021
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
16 sites in 4 countries.
16 sites in 4 countries
Germany6 sites
Universitatsklinikum Bonn
Bonn, 53127
Universitatsklinikum Essen
Essen, 45147
Universitatsklinikum Freiburg
Freiburg im Breisgau, 79106
CTC North GmbH & Co. KG, Am Universitätsklinikum Hamburg-Eppendorf
Hamburg, 20251
Clinical Research Center Hannover
Hanover, 30625
University Hospital Heidelberg
Heidelberg, 69120
Belgium4 sites
Ghent University Hospital
Ghent, 9000
Centre Hospitalier Universitaire de Liege Domaine Universitaire du Sart Tilman
Liège, 4000
Az Sint-Maarten
Mechelen, 2800
Clinical Pharmacology Unit
Merksem, 2170
United States3 sites
WCCT Global, LLC
Cypress, California, 90630
Duke University
Durham, North Carolina, 27710
Ocean Blue Medical Research Center Inc.
Miami Springs, Florida, 33166
United Kingdom3 sites
Wythenshawe Hospital
Greater Manchester, M23 9LT
Royal Liverpool University Hospital
Liverpool, L7 8XP
Guy's Hospital
London, SE1 9RT
About this study
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.
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).
- Conditions
- Crohn Disease, Ulcerative Colitis
- Being tested
- Ustekinumab IV Infusion, Ustekinumab SC Injection, Midazolam 2 mg, Warfarin 10 mg, Vitamin K 10 mg
- Medical subject headings
- Crohn Disease, Colitis, Ulcerative
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ustekinumab IV InfusionDrug
Participants will receive a single IV infusion dose of ustekinumab (dosage to be decided based on body weight) on Day 8.
Ustekinumab SC InjectionDrug
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.
Midazolam 2 mgDrug
Participants will receive 2 milligram per milliliter (mg/ml) syrup of midazolam as a component of the Cytochrome P 450 probe cocktail orally.
Warfarin 10 mgDrug
Participants will receive 10 mg tablet of warfarin as a component of the Cytochrome P 450 probe cocktail orally.
Vitamin K 10 mgDrug
Participants will receive 10 mg tablet of vitamin K as a component of the Cytochrome P 450 probe cocktail orally.
Omeprazole 20 mgDrug
Participants will receive 20 mg capsule of omeprazole as a component of the Cytochrome P 450 probe cocktail orally.
Dextromethorphan 30 mgDrug
Participants will receive 30 mg capsule of dextromethorphan as a component of the Cytochrome P 450 probe cocktail orally.
Caffeine 100 mgDrug
Participants will receive 100 mg tablet of caffeine as a component of the Cytochrome P 450 probe cocktail orally.
| Study group | Role | What they receive |
|---|---|---|
| Crohn's Disease or Ulcerative Colitis Participants: Ustekinumab + Probe Cocktail | Experimental | 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. Receives: Drug: Ustekinumab IV Infusion; Drug: Ustekinumab SC Injection; Drug: Midazolam 2 mg; Drug: Warfarin 10 mg; Drug: Vitamin K 10 mg; Drug: Omeprazole 20 mg; Drug: Dextromethorphan 30 mg; Drug: Caffeine 100 mg |
| Healthy Participants: Probe Cocktail | Experimental | 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. Receives: Drug: Midazolam 2 mg; Drug: Warfarin 10 mg; Drug: Vitamin K 10 mg; Drug: Omeprazole 20 mg; Drug: Dextromethorphan 30 mg; Drug: Caffeine 100 mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Day 1 and 22: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post dose
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.
Measured: Day 1 and 113: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post dose
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.
Measured: Day 1 and 22: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post dose
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.
Measured: Day 1 and 113: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post dose
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.
Measured: Day 1 and 22: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post dose
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.
Measured: Day 1 and 113: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post dose
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.
Measured: Day 1 and 22: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post dose
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.
Measured: Day 1 and 113: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post dose
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.
Measured: 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
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.
Measured: 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 outcomes (6)
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.
Measured: 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
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).
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: Pre-dose and for 12 hours after probe cocktail administration on Day 1, 22 and 113
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.
Measured: Up to Day 176
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Dec 2017
- Study start2 Feb 2018
- Primary completion22 Nov 2021
- Study completion22 Nov 2021
Why it stopped: The study was stopped as all post-marketing commitments had been fulfilled or released
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Crohn DiseaseStudies of the same condition, open and under way.
- More trials run by Janssen Research & Development, LLCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- Janssen Research & Development, LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Janssen Research & Development, LLC Clinical Trial, Study director, Janssen Research & Development, LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03358706
- Sponsor's protocol ID
- CR108352
- Other IDs
- CNTO1275CRD1003, 2017-000831-16, 2017
- Status last verified
- Aug 2025
- First submitted
- 27 Nov 2017
- Last updated
- 21 Aug 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT03358706
- Acronym / sponsor ID
- CR108352
- Conditions
- Crohn Disease, Ulcerative Colitis
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study was stopped as all post-marketing commitments had been fulfilled or released
- Enrolment
- 28 participants (actual)
- Lead sponsor
- Janssen Research & Development, LLCIndustry (pharma, biotech, devices)
- Study start
- 2 Feb 2018 (actual)
- Primary completion
- 22 Nov 2021 (actual)
- Study completion
- 22 Nov 2021 (actual)
- First posted
- 2 Dec 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Crohn's Disease or Ulcerative Colitis Participants: Ustekinumab + Probe Cocktail | Experimental | Drug: Ustekinumab IV Infusion, Drug: Ustekinumab SC Injection, Drug: Midazolam 2 mg, Drug: Warfarin 10 mg, Drug: Vitamin K 10 mg, Drug: Omeprazole 20 mg, Drug: Dextromethorphan 30 mg, Drug: Caffeine 100 mgParticipants 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. |
| Healthy Participants: Probe Cocktail | Experimental | Drug: Midazolam 2 mg, Drug: Warfarin 10 mg, Drug: Vitamin K 10 mg, Drug: Omeprazole 20 mg, Drug: Dextromethorphan 30 mg, Drug: Caffeine 100 mgParticipants 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. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (6 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ustekinumab IV InfusionParticipants will receive a single IV infusion dose of ustekinumab (dosage to be decided based on body weight) on Day 8. | Drug | Crohn's Disease or Ulcerative Colitis Participants: Ustekinumab + Probe Cocktail |
| Ustekinumab SC InjectionParticipants 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. | Drug | Crohn's Disease or Ulcerative Colitis Participants: Ustekinumab + Probe Cocktail |
| Midazolam 2 mgParticipants will receive 2 milligram per milliliter (mg/ml) syrup of midazolam as a component of the Cytochrome P 450 probe cocktail orally. | Drug | Crohn's Disease or Ulcerative Colitis Participants: Ustekinumab + Probe Cocktail, Healthy Participants: Probe Cocktail |
| Warfarin 10 mgParticipants will receive 10 mg tablet of warfarin as a component of the Cytochrome P 450 probe cocktail orally. | Drug | Crohn's Disease or Ulcerative Colitis Participants: Ustekinumab + Probe Cocktail, Healthy Participants: Probe Cocktail |
| Vitamin K 10 mgParticipants will receive 10 mg tablet of vitamin K as a component of the Cytochrome P 450 probe cocktail orally. | Drug | Crohn's Disease or Ulcerative Colitis Participants: Ustekinumab + Probe Cocktail, Healthy Participants: Probe Cocktail |
| Omeprazole 20 mgParticipants will receive 20 mg capsule of omeprazole as a component of the Cytochrome P 450 probe cocktail orally. | Drug | Crohn's Disease or Ulcerative Colitis Participants: Ustekinumab + Probe Cocktail, Healthy Participants: Probe Cocktail |
| Dextromethorphan 30 mgParticipants will receive 30 mg capsule of dextromethorphan as a component of the Cytochrome P 450 probe cocktail orally. | Drug | Crohn's Disease or Ulcerative Colitis Participants: Ustekinumab + Probe Cocktail, Healthy Participants: Probe Cocktail |
| Caffeine 100 mgParticipants will receive 100 mg tablet of caffeine as a component of the Cytochrome P 450 probe cocktail orally. | Drug | Crohn's Disease or Ulcerative Colitis Participants: Ustekinumab + Probe Cocktail, Healthy Participants: Probe Cocktail |
Primary outcome
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)
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
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)
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
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)
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
(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)
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
(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)
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
(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)
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
(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)
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
(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)
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
(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)
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
(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)
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
(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.
6 secondary outcomes
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)
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
CD and UC Participants: Terminal Half-Life (T1/2) of Cytochrome P450 Probe Substrates (Midazolam, Omeprazole, Dextromethorphan, S-warfarin and Caffeine)
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
CD and UC Participants: Apparent Total Systemic Clearance (CL/F) of Cytochrome P450 Probe Substrates (Midazolam, Omeprazole, Dextromethorphan, S-warfarin and Caffeine)
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
CD and UC Participants: Apparent Volume of Distribution (Vz/F) of Cytochrome P450 Probe Substrates (Midazolam, Omeprazole, Dextromethorphan, S-warfarin and Caffeine)
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
CD and UC Participants: Twelve Hour Urine Dextromethorphan to Dextrorphan Ratio
Time frame: Pre-dose and for 12 hours after probe cocktail administration on Day 1, 22 and 113
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Time frame: Up to Day 176
Results and safety
The study was stopped early (reason given: The study was stopped as all post-marketing commitments had been fulfilled or released). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Aug 2025.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Janssen Research & Development, LLC Clinical Trial study director
Janssen Research & Development, LLC
16 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Ustekinumab IV Infusion, Ustekinumab SC Injection and Midazolam 2 mg in people with Crohn Disease and Ulcerative Colitis, run by Janssen Research & Development, LLC at 16 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 21 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 16 sites in Germany, Belgium, United States, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: The study was stopped as all post-marketing commitments had been fulfilled or released). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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) (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). The study lists 10 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Aug 2025.