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

Sponsor

Janssen Research & Development, LLC (Industry)

Overall Status

Completed

CT.gov ID

NCT02397382

Collaborator

(none)

Enrollment

Locations

Arm

14.5

Actual Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Psoriasis	Drug: Guselkumab Drug: Midazolam Drug: Warfarin Drug: Omeprazole Drug: Dextromethorphan Drug: Caffeine	Phase 1

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 Design

Study Type:

Interventional

Actual Enrollment :

16 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jun 18, 2015

Actual Primary Completion Date :

Aug 31, 2016

Actual Study Completion Date :

Aug 31, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Guselkumab and Cytochrome P450 Probe Cocktail 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 Guselkumab will be administered as a single dose of 200 milligram (mg) by subcutaneous injection (2100 mg) on Day 8. Drug: Midazolam* Midazolam will be administered orally as probe cocktail containing 0.03 mg per kilogram (kg) once on Day 1, 15 and 36. Drug: Warfarin Warfarin will be administered orally as probe cocktail containing 10 mg once on Day 1, 15 and 36. Drug: Omeprazole Omeprazole will be administered orally as probe cocktail containing 20 mg once on Day 1, 15 and 36. Drug: Dextromethorphan Dextromethorphan will be administered orally as probe cocktail containing 30 mg once on Day 1, 15 and 36. Drug: Caffeine Caffeine will be administered orally as probe cocktail containing 100 mg once on Day 1, 15 and 36.

Arm

Intervention/Treatment

Experimental: Guselkumab and Cytochrome P450 Probe Cocktail

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

Guselkumab will be administered as a single dose of 200 milligram (mg) by subcutaneous injection (2*100 mg) on Day 8.

Drug: Midazolam

Midazolam will be administered orally as probe cocktail containing 0.03 mg per kilogram (kg) once on Day 1, 15 and 36.

Drug: Warfarin

Warfarin will be administered orally as probe cocktail containing 10 mg once on Day 1, 15 and 36.

Drug: Omeprazole

Omeprazole will be administered orally as probe cocktail containing 20 mg once on Day 1, 15 and 36.

Drug: Dextromethorphan

Dextromethorphan will be administered orally as probe cocktail containing 30 mg once on Day 1, 15 and 36.

Drug: Caffeine

Caffeine will be administered orally as probe cocktail containing 100 mg once on Day 1, 15 and 36.

Outcome Measures

Primary Outcome Measures

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

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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts 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)

Contacts and Locations

Locations

	City	State	Country
1	Anniston	Alabama	United States
2	North Hollywood	California	United States
3	Orlando	Florida	United States
4	Atlanta	Georgia	United States
5	High Point	North Carolina	United States
6	Duncansville	Pennsylvania	United States
7	Pittsburgh	Pennsylvania	United States
8	San Antonio	Texas	United States