A Study to Evaluate the Effect of a Single Dose of CNTO 136 (Sirukumab) on CYP450 Enzyme Activities After Subcutaneous Administration in Patients With Rheumatoid Arthritis
Condition: Arthritis, Rheumatoid
MeSH terms: Arthritis; Arthritis, Rheumatoid
Study type: Interventional
Phase: Phase 1

Summary: 
      The main purpose of this study is to evaluate the potential effects of a single dose of
      sirukumab on the pharmacokinetics (what the body does to a drug) of study agents that are
      specific for cytochrome P450 (CYP) enzymes (CYP3A4, CYP2C9, CYP2C19, and CYP1A2) in patients
      with active rheumatoid arthritis (RA). This study will also assess the safety and
      tolerability of a single subcutaneous (SC, under the skin) dose of sirukumab in patients with
      active RA.
    

Detailed description: 
      This is an open-label (all patients and study personnel will know the identity of the
      administered study agents), multi-center, drug-drug interaction study. Approximately 18
      patients may be enrolled in this study, and there will be one treatment group. All patients
      will receive a single subcutaneous (SC) dose of sirukumab. Cytochrome P450 (CYP)
      enzyme-specific study agents (5-probe cocktail) will consist of oral doses of midazolam,
      warfarin/vitamin K, omeprazole, and caffeine administered on 4 separate occasions throughout
      the study. A blood sample for CYP genetic analysis (genotyping) will be collected during
      screening from all prospective patients to determine eligibility for the study. Participation
      in CYP genotyping prescreening is mandatory for all patients. The CYP genotyping blood sample
      will not be used for any additional genetic research and will be destroyed after completion
      of this study. The total duration of study participation will be approximately 12 weeks for
      all patients included in the study, including a screening visit up to 4 weeks prior to first
      study agent administration. Patients will have five in-patient periods, four consisting of 3
      days and 2 nights each and one consisting of 2 days and 1 night. Patients safety will be
      monitored throughout the study, and there will be approximately 7 weeks of safety follow-up
      after sirukumab administration.
    

Intervention name(s): Sirukumab; Midazolam; Warfarin; Vitamin K; Omeprazole; Caffeine
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Drug
Intervention description(s): Type=exact number, unit=mg, number=300, form=solution for injection, route=subcutaneous use, on Day 8; Type=exact number, unit=mg/kg, number 0.03, form=commercially available form, route=oral use, on Days 1, 15, 29, and 50; Type=exact number, unit=mg, number= 10, form=commercially available form, route=oral use, on Days 1, 15, 29, and 50; Type=exact number, unit=mg, number =10, form=commercially available form, route=oral use, on Days 1, 15, 29, and 50; Type=exact number, unit=mg, number=20, form=commercially available form, route=oral use, on Days 1, 15, 29, and 50; Type=exact number, unit=mg, number=100, form=commercially available form, route=oral use, on Days 1, 15, 29, and 50
Intervention MeSH terms: Vitamin K; Midazolam; Caffeine; Omeprazole; Warfarin
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: Rheumatoid arthritis; sirukumab; CNTO 136; CYP450 enzyme; anti-interleukin-6 monoclonal antibody