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

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Phase 1, Open-label, Drug Interaction Study to Evaluate the Effect of Guselkumab (CNTO 1959) on Cytochrome P450 Enzyme Activities Following a Single Subcutaneous Administration in Subjects With Moderate to Severe Plaque-type Psoriasis

Conditions
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Psoriasis

Intervention / Treatment
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* Drug: Guselkumab
* Drug: Midazolam
* Drug: Warfarin
* Drug: Omeprazole
* Drug: Dextromethorphan
* Drug: Caffeine


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Guselkumab and Cytochrome P450 Probe Cocktail<br>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. | Drug: Guselkumab<br>* Guselkumab will be administered as a single dose of 200 milligram (mg) by subcutaneous injection (2*100 mg) on Day 8.<br>Drug: Midazolam<br>* Midazolam will be administered orally as probe cocktail containing 0.03 mg per kilogram (kg) once on Day 1, 15 and 36.<br>Drug: Warfarin<br>* Warfarin will be administered orally as probe cocktail containing 10 mg once on Day 1, 15 and 36.<br>Drug: Omeprazole<br>* Omeprazole will be administered orally as probe cocktail containing 20 mg once on Day 1, 15 and 36.<br>Drug: Dextromethorphan<br>* Dextromethorphan will be administered orally as probe cocktail containing 30 mg once on Day 1, 15 and 36.<br>Drug: Caffeine<br>* Caffeine will be administered orally as probe cocktail containing 100 mg once on Day 1, 15 and 36.<br>|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Psoriasis, Guselkumab, Cytochromes P450