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

NCT ID: NCT03358706

Last Updated: 2025-08-21

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 28 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-02-02
• Study Completion Date: 2021-11-22

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).

Conditions

Crohn Disease; Ulcerative Colitis

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Crohn's Disease or Ulcerative Colitis Participants: Ustekinumab + Probe Cocktail

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.

Group Type: EXPERIMENTAL

Ustekinumab IV Infusion

Intervention Type: DRUG

Participants will receive a single IV infusion dose of ustekinumab (dosage to be decided based on body weight) on Day 8.

Ustekinumab SC Injection

Intervention Type: DRUG

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 mg

Intervention Type: DRUG

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 mg

Intervention Type: DRUG

Participants will receive 10 mg tablet of warfarin as a component of the Cytochrome P 450 probe cocktail orally.

Vitamin K 10 mg

Intervention Type: DRUG

Participants will receive 10 mg tablet of vitamin K as a component of the Cytochrome P 450 probe cocktail orally.

Omeprazole 20 mg

Intervention Type: DRUG

Participants will receive 20 mg capsule of omeprazole as a component of the Cytochrome P 450 probe cocktail orally.

Dextromethorphan 30 mg

Intervention Type: DRUG

Participants will receive 30 mg capsule of dextromethorphan as a component of the Cytochrome P 450 probe cocktail orally.

Caffeine 100 mg

Intervention Type: DRUG

Participants will receive 100 mg tablet of caffeine as a component of the Cytochrome P 450 probe cocktail orally.

Healthy Participants: Probe Cocktail

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.

Group Type: EXPERIMENTAL

Midazolam 2 mg

Intervention Type: DRUG

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 mg

Intervention Type: DRUG

Participants will receive 10 mg tablet of warfarin as a component of the Cytochrome P 450 probe cocktail orally.

Vitamin K 10 mg

Intervention Type: DRUG

Participants will receive 10 mg tablet of vitamin K as a component of the Cytochrome P 450 probe cocktail orally.

Omeprazole 20 mg

Intervention Type: DRUG

Participants will receive 20 mg capsule of omeprazole as a component of the Cytochrome P 450 probe cocktail orally.

Dextromethorphan 30 mg

Intervention Type: DRUG

Participants will receive 30 mg capsule of dextromethorphan as a component of the Cytochrome P 450 probe cocktail orally.

Caffeine 100 mg

Intervention Type: DRUG

Participants will receive 100 mg tablet of caffeine as a component of the Cytochrome P 450 probe cocktail orally.

Interventions

Ustekinumab IV Infusion

Participants will receive a single IV infusion dose of ustekinumab (dosage to be decided based on body weight) on Day 8.

Intervention Type: DRUG

Ustekinumab SC Injection

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

Midazolam 2 mg

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

Warfarin 10 mg

Participants will receive 10 mg tablet of warfarin as a component of the Cytochrome P 450 probe cocktail orally.

Intervention Type: DRUG

Vitamin K 10 mg

Participants will receive 10 mg tablet of vitamin K as a component of the Cytochrome P 450 probe cocktail orally.

Intervention Type: DRUG

Omeprazole 20 mg

Participants will receive 20 mg capsule of omeprazole as a component of the Cytochrome P 450 probe cocktail orally.

Intervention Type: DRUG

Dextromethorphan 30 mg

Participants will receive 30 mg capsule of dextromethorphan as a component of the Cytochrome P 450 probe cocktail orally.

Intervention Type: DRUG

Caffeine 100 mg

Participants will receive 100 mg tablet of caffeine as a component of the Cytochrome P 450 probe cocktail orally.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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

• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Janssen Research & Development, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen Research & Development, LLC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Research & Development, LLC

Locations

WCCT Global, LLC

Cypress, California, United States

Ocean Blue Medical Research Center Inc.

Miami Springs, Florida, United States

Duke University

Durham, North Carolina, United States

Ghent University Hospital

Ghent, , Belgium

Centre Hospitalier Universitaire de Liege Domaine Universitaire du Sart Tilman

Liège, , Belgium

Az Sint-Maarten

Mechelen, , Belgium

Clinical Pharmacology Unit

Merksem, , Belgium

Universitatsklinikum Bonn

Bonn, , Germany

Universitatsklinikum Essen

Essen, , Germany

Universitatsklinikum Freiburg

Freiburg im Breisgau, , Germany

CTC North GmbH & Co. KG, Am Universitätsklinikum Hamburg-Eppendorf

Hamburg, , Germany

Clinical Research Center Hannover

Hanover, , Germany

University Hospital Heidelberg

Heidelberg, , Germany

Wythenshawe Hospital

Greater Manchester, , United Kingdom

Royal Liverpool University Hospital

Liverpool, , United Kingdom

Guy's Hospital

London, , United Kingdom

Countries

United States; Belgium; Germany; United Kingdom

Other Identifiers

CNTO1275CRD1003

Identifier Type: OTHER

Identifier Source: secondary_id

2017-000831-16

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CR108352

Identifier Type: -

Identifier Source: org_study_id