Pharmacokinetic Study to Evaluate the Effect of a Single Dose of Guselkumab (CNTO 1959) on CYP 450 Enzyme Activities After Subcutaneous Administration in Participants With Psoriasis

Janssen (J&J Innovative Medicine)

Status and phase: Completed; Phase 1

Conditions: Psoriasis

Treatments: Drug: Caffeine; Drug: Warfarin; Drug: Guselkumab; Drug: Midazolam; Drug: Dextromethorphan; Drug: Omeprazole

Study type: Interventional

Funder types: Industry

Identifiers

NCT02397382

CNTO1959PSO1003 (Other Identifier)

CR106796

Details and patient eligibility

About

The purpose of this study is to evaluate the potential effects of a single dose of 200 milligram (mg) guselkumab on the plasma concentrations of a cocktail of representative probe substrates of Cytochrome P450 isozymes (CYP3A4, CYP2C9, CYP2C19, CYP2D6, and CYP1A2) in participants with moderate to severe psoriasis.

Full description

This is an open-label, multi-center study. The total duration of study will be approximately 17 weeks per participant, including Screening phase (up to 4 weeks prior to first probe cocktail administration). Participants will have 4 in-patient periods on Day 1, 8, 15 and 36 (3 periods consisting of 3 days and 2 nights each and 1 consisting of 2 days and 1 night) followed by follow up period (up to Day 92). All Participants will receive a single 200 mg subcutaneous (SC) injection (2*100 mg) of guselkumab on Day 8 and probe cocktail on Days 1, 15 and 36. Blood samples will be collected for the evaluation of pharmacokinetics and immunogenicity at pre-dose and post-dose of study treatment. Participants' safety will be monitored throughout the study.

Enrollment: 16 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Have a diagnosis of plaque-type psoriasis with or without psoriatic arthritis (PsA) for at least 6 months before Day 1
• Have a Psoriasis Area and Severity Index (PASI) greater than or equal to (>=) 12 at Screening
• Have an Investigator's Global Assessment (IGA) >= 3 at Screening
• Have an involved body surface area (BSA) >= 10 percent (%) at Screening
• Be a candidate for phototherapy or systemic treatment for psoriasis

Exclusion criteria

• Has a history of or current signs or symptoms of severe, progressive, or uncontrolled renal, hepatic, cardiac (including unstable cardiovascular disease, defined as a recent clinical deterioration (example, unstable angina, rapid atrial fibrillation) in the last 3 months or a cardiac hospitalization within the last 3 months), vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, bleeding disorder, rheumatologic, psychiatric, or metabolic disturbances
• Have a pulse oximetry value less than (<) 94 % at Screening
• Genetically determined poor metabolizers of CYP2C9, CYP2C19, and CYP2D6 substrates
• Is currently undergoing or has previously undergone allergy immunotherapy for a history of anaphylactic reactions
• Has a transplanted organ (with exception of a corneal transplant greater than (>) 3 months before Day 1)

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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16 participants in 1 patient group

Guselkumab and Cytochrome P450 Probe Cocktail

Experimental group

Description:

Participants will be administered single dose of Guselkumab 200 milligram (mg) by subcutaneous injection (2\*100 mg) on Day 8 and Cytochrome P450 probe cocktail consist of midazolam, warfarin/vitamin K, omeprazole, dextromethorphan and caffeine orally once on Day 1,15 and 36.

Treatment:

Drug: Dextromethorphan

Drug: Omeprazole

Drug: Warfarin

Drug: Midazolam

Drug: Caffeine

Drug: Guselkumab