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

• Register: ClinicalTrials.gov
• Last refreshed on: 2 August 2023
• Main ID: NCT03358706
• Date of registration: 27/11/2017
• Prospective Registration: Yes
• Primary sponsor: Janssen Research & Development, LLC
• Public 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
• Scientific 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.
• Date of first enrolment: February 2, 2018
• Target sample size: 57
• Recruitment status: Suspended
• URL: https://clinicaltrials.gov/ct2/show/NCT03358706
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Parallel Assignment. Primary purpose: Other. Masking: None (Open Label).
• Phase: Phase 1

Countries of recruitment

Austria, Belgium, Denmark, Germany, Sweden, United Kingdom, United States

Contacts

• Name: Janssen Research & Development, LLC Clinical Trial
• Affiliation: Janssen Research & Development, LLC

Key inclusion & exclusion 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



Age minimum: 18 Years
Age maximum: 75 Years
Gender: All

Health Condition(s) or Problem(s) studied

Crohn Disease

Ulcerative Colitis

Intervention(s)

Drug: Dextromethorphan 30 mg

Drug: Warfarin 10 mg

Drug: Midazolam 2 mg

Drug: Caffeine 100 mg

Drug: Omeprazole 20 mg

Drug: Ustekinumab IV Infusion

Drug: Ustekinumab SC Injection

Drug: Vitamin K 10 mg

Primary Outcome(s)

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

Secondary Outcome(s)

Number of Participants With Treatment-Emergent Adverse Events (TEAEs) [Time Frame: Up to Day 176]

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: 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: 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]

Secondary ID(s)

CR108352

2017-000831-16

CNTO1275CRD1003

Source(s) of Monetary Support

Please refer to primary and secondary sponsors