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

Janssen (J&J Innovative Medicine)

Status and phase: Terminated; Phase 1

Conditions: Ulcerative Colitis; Crohn Disease

Treatments: Drug: Midazolam 2 mg; Drug: Omeprazole 20 mg; Drug: Warfarin 10 mg; Drug: Ustekinumab SC Injection; Drug: Caffeine 100 mg; Drug: Vitamin K 10 mg; Drug: Ustekinumab IV Infusion; Drug: Dextromethorphan 30 mg

Study type: Interventional

Funder types: Industry

Identifiers

NCT03358706

2017-000831-16 (EudraCT Number)

CNTO1275CRD1003 (Other Identifier)

CR108352

Details and patient eligibility

About

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).

Enrollment: 28 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and 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

Trial design

Primary purpose: Other

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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28 participants in 2 patient groups

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

Experimental group

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.

Treatment:

Drug: Dextromethorphan 30 mg

Drug: Ustekinumab IV Infusion

Drug: Caffeine 100 mg

Drug: Vitamin K 10 mg

Drug: Ustekinumab SC Injection

Drug: Omeprazole 20 mg

Drug: Warfarin 10 mg

Drug: Midazolam 2 mg

Healthy Participants: Probe Cocktail

Experimental group

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.

Treatment:

Drug: Dextromethorphan 30 mg

Drug: Caffeine 100 mg

Drug: Vitamin K 10 mg

Drug: Omeprazole 20 mg

Drug: Warfarin 10 mg

Drug: Midazolam 2 mg