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

NCT02397382 | Completed Phase 1

• 2 other identifiers: CR106796CNTO1959PSO1003
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 8

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.

Conditions

Psoriasis

Keywords

Psoriasis; Guselkumab; Cytochromes P450

Outcome Measures

Primary Outcomes (6)

• 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

• 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

• 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

• 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

• Serum Concentration of Guselkumab

  The observed serum concentration of Guselkumab.

  Pre-dose on Day 8 and up to Day 92

• Number of Participants with antibody to CNTO1959

  The frequency of anti-CNTO1959 antibodies.

  Pre-dose on Day 8 and up to Day 92

Secondary Outcomes (1)

• Number of Participants with Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

  Up to 92 Days

Study Arms (1)

Guselkumab and Cytochrome P450 Probe Cocktail

EXPERIMENTAL

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; Drug: Midazolam; Drug: Warfarin; Drug: Omeprazole; Drug: Dextromethorphan; Drug: Caffeine

Interventions

Guselkumab DRUG

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

Guselkumab and Cytochrome P450 Probe Cocktail

Midazolam DRUG

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

Guselkumab and Cytochrome P450 Probe Cocktail

Warfarin DRUG

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

Guselkumab and Cytochrome P450 Probe Cocktail

Omeprazole DRUG

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

Guselkumab and Cytochrome P450 Probe Cocktail

Dextromethorphan DRUG

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

Guselkumab and Cytochrome P450 Probe Cocktail

Caffeine DRUG

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

Guselkumab and Cytochrome P450 Probe Cocktail

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (8)

Unknown Facility

Anniston, Alabama, United States

Location

Unknown Facility

North Hollywood, California, United States

Location

Unknown Facility

Orlando, Florida, United States

Location

Unknown Facility

Atlanta, Georgia, United States

Location

Unknown Facility

High Point, North Carolina, United States

Location

Unknown Facility

Duncansville, Pennsylvania, United States

Location

Unknown Facility

Pittsburgh, Pennsylvania, United States

Location

Unknown Facility

San Antonio, Texas, United States

Location

Related Publications (1)

• 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.

  PMID: 32407591 DERIVED

Related 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

MeSH Terms

Conditions

Psoriasis

Interventions

guselkumab; Midazolam; Warfarin; Omeprazole; Dextromethorphan; Caffeine

Condition Hierarchy (Ancestors)

Skin Diseases, Papulosquamous; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; 4-Hydroxycoumarins; Coumarins; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; 2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Benzimidazoles; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Xanthines; Purinones; Purines

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 19, 2015
• First Posted: March 25, 2015
• Study Start: June 18, 2015
• Primary Completion: August 31, 2016
• Study Completion: August 31, 2016
• Last Updated: September 20, 2017

Record last verified: 2017-09

Locations

US (8)