Clinical trial NCT02397382: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Psoriasis
Keywords: Psoriasis
Guselkumab
Cytochromes P450
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2015-03-25
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax)
timeFrame: Screening up to 96 hours on Day 1, 15 and 36
measure: Time to Reach Maximum Concentration (Tmax)
timeFrame: Screening up to 96 hours on Day 1, 15 and 36
measure: Area Under the Plasma Concentration-time Curve From Time Zero to Last Quantifiable Time (AUC [0-last])
timeFrame: Screening up to 96 hours on Day 1, 15 and 36
measure: Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC [0 - infinity])
timeFrame: Screening up to 96 hours on Day 1, 15 and 36
measure: Serum Concentration of Guselkumab
timeFrame: Pre-dose on Day 8 and up to Day 92
measure: Number of Participants with antibody to CNTO1959
timeFrame: Pre-dose on Day 8 and up to Day 92
Secondary outcomes:
measure: Number of Participants with Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
timeFrame: Up to 92 Days
Other outcomes:
Locations:
city: Anniston
country: United States
state: Alabama
city: North Hollywood
country: United States
state: California
city: Orlando
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: High Point
country: United States
state: North Carolina
city: Duncansville
country: United States
state: Pennsylvania
city: Pittsburgh
country: United States
state: Pennsylvania
city: San Antonio
country: United States
state: Texas
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Zhu Y, Xu Y, Zhuang Y, Piantone A, Shu C, Chen D, Zhou H, Xu Z, Sharma A. Evaluating Potential Disease-Mediated Protein-Drug Interactions in Patients With Moderate-to-Severe Plaque Psoriasis Receiving Subcutaneous Guselkumab. Clin Transl Sci. 2020 Nov;13(6):1217-1226. doi: 10.1111/cts.12807. Epub 2020 May 28.