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

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

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02397382

Enrollment

Registered

2015-03-25

Start date

2015-06-18

Completion date

2016-08-31

Last updated

2017-09-20

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Psoriasis

Keywords

Psoriasis, Guselkumab, Cytochromes P450

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.

Interventions

DRUGGuselkumab

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

DRUGMidazolam

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

DRUGWarfarin

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

DRUGOmeprazole

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

DRUGDextromethorphan

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

DRUGCaffeine

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

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 65 Years

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)

Design outcomes

Primary

Measure	Time frame	Description
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.
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.
Number of Participants with antibody to CNTO1959	Pre-dose on Day 8 and up to Day 92	The frequency of anti-CNTO1959 antibodies.
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.

Secondary

Measure	Time frame	Description
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.

Countries

United States

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 18, 2026