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

Phase 1

Completed

• Conditions: Psoriasis
• Interventions: Drug: Guselkumab; Drug: Midazolam; Drug: Warfarin; Drug: Omeprazole; Drug: Dextromethorphan; Drug: Caffeine

• Registration Number: NCT02397382
• Lead Sponsor: Janssen Research & Development, LLC

Brief Summary

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.

Detailed 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.

Study Timeline

• Study First Submitted: 2015-03-19
• Study First Submitted QC: 2015-03-19
• Study First Posted: 2015-03-25
• Study Start: 2015-06-18
• Primary Completion: 2016-08-31
• Study Completion: 2016-08-31
• Status Verified: 2017-09
• Last Update Submitted: 2017-09-19
• Last Update Posted: 2017-09-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 16

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

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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)

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Guselkumab and Cytochrome P450 Probe Cocktail	Warfarin	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.
Guselkumab and Cytochrome P450 Probe Cocktail	Dextromethorphan	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.
Guselkumab and Cytochrome P450 Probe Cocktail	Caffeine	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.
Guselkumab and Cytochrome P450 Probe Cocktail	Guselkumab	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.
Guselkumab and Cytochrome P450 Probe Cocktail	Midazolam	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.
Guselkumab and Cytochrome P450 Probe Cocktail	Omeprazole	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.

Primary Outcome Measures

Name	Time	Method
Maximum Observed Plasma Concentration (Cmax)	Screening up to 96 hours on Day 1, 15 and 36	The Cmax is the maximum observed plasma concentration of Midazolam, Omeprazole, Dextromethorphan, Caffeine and S-warfarin.
Time to Reach Maximum Concentration (Tmax)	Screening up to 96 hours on Day 1, 15 and 36	The Tmax is time to reach the maximum observed plasma concentration of Midazolam, Omeprazole, Dextromethorphan, Caffeine and S-warfarin.
Area Under the Plasma Concentration-time Curve From Time Zero to Last Quantifiable Time (AUC [0-last])	Screening up to 96 hours on Day 1, 15 and 36	The AUC (0-last) is area under the plasma concentration-time curve from time zero to time of last quantifiable concentration of Midazolam, Omeprazole, Dextromethorphan, Caffeine and S-warfarin.
Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC [0 - infinity])	Screening up to 96 hours on Day 1, 15 and 36	The AUC (0-infinity) is the area under the plasma concentration-time curve from time zero to extrapolated infinite time.
Serum Concentration of Guselkumab	Pre-dose on Day 8 and up to Day 92	The observed serum concentration of Guselkumab.
Number of Participants with antibody to CNTO1959	Pre-dose on Day 8 and up to Day 92	The frequency of anti-CNTO1959 antibodies.

Secondary Outcome Measures

Name	Time	Method
Number of Participants with Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)	Up to 92 Days	The incidence of TEAEs and SAEs from the screening visit and until the follow-up contact will be will be summarized by treatment period.