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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

Primary Purpose

Psoriasis

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Guselkumab
Midazolam
Warfarin
Omeprazole
Dextromethorphan
Caffeine
Sponsored by
Janssen Research & Development, LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Psoriasis focused on measuring Psoriasis, Guselkumab, Cytochromes P450

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept 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)

Sites / Locations

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Guselkumab and Cytochrome P450 Probe Cocktail

Arm Description

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.

Outcomes

Primary Outcome Measures

Maximum Observed Plasma Concentration (Cmax)
The Cmax is the maximum observed plasma concentration of Midazolam, Omeprazole, Dextromethorphan, Caffeine and S-warfarin.
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.
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.
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.
Serum Concentration of Guselkumab
The observed serum concentration of Guselkumab.
Number of Participants with antibody to CNTO1959
The frequency of anti-CNTO1959 antibodies.

Secondary Outcome Measures

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.

Full Information

First Posted
March 19, 2015
Last Updated
September 19, 2017
Sponsor
Janssen Research & Development, LLC
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1. Study Identification

Unique Protocol Identification Number
NCT02397382
Brief Title
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

2. Study Status

Record Verification Date
September 2017
Overall Recruitment Status
Completed
Study Start Date
June 18, 2015 (Actual)
Primary Completion Date
August 31, 2016 (Actual)
Study Completion Date
August 31, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Janssen Research & Development, LLC

4. Oversight

Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Psoriasis
Keywords
Psoriasis, Guselkumab, Cytochromes P450

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
16 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Guselkumab and Cytochrome P450 Probe Cocktail
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Guselkumab
Intervention Description
Guselkumab will be administered as a single dose of 200 milligram (mg) by subcutaneous injection (2*100 mg) on Day 8.
Intervention Type
Drug
Intervention Name(s)
Midazolam
Intervention Description
Midazolam will be administered orally as probe cocktail containing 0.03 mg per kilogram (kg) once on Day 1, 15 and 36.
Intervention Type
Drug
Intervention Name(s)
Warfarin
Intervention Description
Warfarin will be administered orally as probe cocktail containing 10 mg once on Day 1, 15 and 36.
Intervention Type
Drug
Intervention Name(s)
Omeprazole
Intervention Description
Omeprazole will be administered orally as probe cocktail containing 20 mg once on Day 1, 15 and 36.
Intervention Type
Drug
Intervention Name(s)
Dextromethorphan
Intervention Description
Dextromethorphan will be administered orally as probe cocktail containing 30 mg once on Day 1, 15 and 36.
Intervention Type
Drug
Intervention Name(s)
Caffeine
Intervention Description
Caffeine will be administered orally as probe cocktail containing 100 mg once on Day 1, 15 and 36.
Primary Outcome Measure Information:
Title
Maximum Observed Plasma Concentration (Cmax)
Description
The Cmax is the maximum observed plasma concentration of Midazolam, Omeprazole, Dextromethorphan, Caffeine and S-warfarin.
Time Frame
Screening up to 96 hours on Day 1, 15 and 36
Title
Time to Reach Maximum Concentration (Tmax)
Description
The Tmax is time to reach the maximum observed plasma concentration of Midazolam, Omeprazole, Dextromethorphan, Caffeine and S-warfarin.
Time Frame
Screening up to 96 hours on Day 1, 15 and 36
Title
Area Under the Plasma Concentration-time Curve From Time Zero to Last Quantifiable Time (AUC [0-last])
Description
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.
Time Frame
Screening up to 96 hours on Day 1, 15 and 36
Title
Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC [0 - infinity])
Description
The AUC (0-infinity) is the area under the plasma concentration-time curve from time zero to extrapolated infinite time.
Time Frame
Screening up to 96 hours on Day 1, 15 and 36
Title
Serum Concentration of Guselkumab
Description
The observed serum concentration of Guselkumab.
Time Frame
Pre-dose on Day 8 and up to Day 92
Title
Number of Participants with antibody to CNTO1959
Description
The frequency of anti-CNTO1959 antibodies.
Time Frame
Pre-dose on Day 8 and up to Day 92
Secondary Outcome Measure Information:
Title
Number of Participants with Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Description
The incidence of TEAEs and SAEs from the screening visit and until the follow-up contact will be will be summarized by treatment period.
Time Frame
Up to 92 Days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Janssen Research & Development, LLC Clinical Trial
Organizational Affiliation
Janssen Research & Development, LLC
Official's Role
Study Director
Facility Information:
City
Anniston
State/Province
Alabama
Country
United States
City
North Hollywood
State/Province
California
Country
United States
City
Orlando
State/Province
Florida
Country
United States
City
Atlanta
State/Province
Georgia
Country
United States
City
High Point
State/Province
North Carolina
Country
United States
City
Duncansville
State/Province
Pennsylvania
Country
United States
City
Pittsburgh
State/Province
Pennsylvania
Country
United States
City
San Antonio
State/Province
Texas
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
32407591
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.
Results Reference
derived
Links:
URL
http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_JNJ_7051&studyid=9675&filename=CR106796_CSR.pdf
Description
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

Learn more about this trial

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

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