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

Psoriasis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02397382
• Other study ID #: CR106796
• Secondary ID: CNTO1959PSO1003
• Status: Completed
• Phase: Phase 1
• First received: March 19, 2015
• Last updated: September 19, 2017
• Start date: June 18, 2015
• Est. completion date: August 31, 2016

Study information

• Verified date: September 2017
• Source: Janssen Research & Development, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: August 31, 2016
• Est. primary completion date: August 31, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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)

Related Conditions & MeSH terms

• Psoriasis

Intervention

Drug:
• Guselkumab
Guselkumab will be administered as a single dose of 200 milligram (mg) by subcutaneous injection (2*100 mg) on Day 8.
• Midazolam
Midazolam will be administered orally as probe cocktail containing 0.03 mg per kilogram (kg) once on Day 1, 15 and 36.
• Warfarin
Warfarin will be administered orally as probe cocktail containing 10 mg once on Day 1, 15 and 36.
• Omeprazole
Omeprazole will be administered orally as probe cocktail containing 20 mg once on Day 1, 15 and 36.
• Dextromethorphan
Dextromethorphan will be administered orally as probe cocktail containing 30 mg once on Day 1, 15 and 36.
• Caffeine
Caffeine will be administered orally as probe cocktail containing 100 mg once on Day 1, 15 and 36.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	Serum Concentration of Guselkumab	The observed serum concentration of Guselkumab.	Pre-dose on Day 8 and up to Day 92
Primary	Number of Participants with antibody to CNTO1959	The frequency of anti-CNTO1959 antibodies.	Pre-dose on Day 8 and up to Day 92
Secondary	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

External Links

•   A Phase I, 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