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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

This study is currently recruiting participants.
Verified June 2013 by Janssen Research & Development, LLC
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT01636557
First received: July 6, 2012
Last updated: June 18, 2013
Last verified: June 2013
History of Changes
  Purpose

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.


Condition Intervention Phase
Arthritis, Rheumatoid
 Drug: Sirukumab
Drug: Midazolam
Drug: Warfarin
Drug: Vitamin K
Drug: Omeprazole
Drug: Caffeine
 Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: A Phase I, Open-label, Drug Interaction Study to Evaluate the Effect of a Single-dose of CNTO 136 (Sirukumab) on CYP450 Enzyme Activities After Subcutaneous Administration in Subjects With Rheumatoid Arthritis

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Janssen Research & Development, LLC:

Primary Outcome Measures:
  • Pharmacokinetics of midazolam, S-warfarin, omeprazole, and caffeine [ Time Frame: Up to 54 days ] [ Designated as safety issue: No ]
    Pharmacokinetic parameters will include the maximum observed plasma concentration (Cmax), time to reach the maximum observed plasma concentration (Tmax), area under the plasma concentration-time curve from time 0 to time of the last quantifiable concentration (AUClast), area under the plasma concentration-time curve from time 0 to 96 hours (AUC0-96h) (S-warfarin only), area under the plasma concentration versus time curve from time 0 to infinity with extrapolation of the terminal phase (AUCinf).


Secondary Outcome Measures:
  • Number of participants with adverse events [ Time Frame: Up to 12 weeks ] [ Designated as safety issue: No ]
  • Clinical laboratory assessments [ Time Frame: Up to 12 weeks ] [ Designated as safety issue: No ]
    Blood and urine tests

  • Electrocardiograms (ECGs) [ Time Frame: Up to 12 weeks ] [ Designated as safety issue: No ]
  • Vital signs evaluations [ Time Frame: Up to 12 weeks ] [ Designated as safety issue: No ]
  • Physical examination [ Time Frame: Up to 12 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 18
Study Start Date: October 2012
Estimated Study Completion Date: November 2013
Estimated Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Sirukumab and 5-probe cocktail
The 5-probe cocktail will consist of oral doses of midazolam, warfarin/vitamin K, omeprazole, and caffeine.
 Drug: Sirukumab
Type=exact number, unit=mg, number=300, form=solution for injection, route=subcutaneous use, on Day 8
Drug: Midazolam
Type=exact number, unit=mg/kg, number 0.03, form=commercially available form, route=oral use, on Days 1, 15, 29, and 50
Drug: Warfarin
Type=exact number, unit=mg, number= 10, form=commercially available form, route=oral use, on Days 1, 15, 29, and 50
Drug: Vitamin K
Type=exact number, unit=mg, number =10, form=commercially available form, route=oral use, on Days 1, 15, 29, and 50
Drug: Omeprazole
Type=exact number, unit=mg, number=20, form=commercially available form, route=oral use, on Days 1, 15, 29, and 50
Drug: Caffeine
Type=exact number, unit=mg, number=100, form=commercially available form, route=oral use, on Days 1, 15, 29, and 50

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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Have a body mass index of 18 kg/m2 to 29.9 kg/m2, inclusive, and a body weight of 60 kg to 110 kg, inclusive, if a man, and 50 kg to 100 kg, inclusive, if a woman
  • Have a diagnosis of rheumatoid arthritis (RA) for at least 3 months before screening
  • If using nonsteroidal anti-inflammatory drugs (NSAIDs) or other analgesics, must be on a stable dose for at least 2 weeks prior to Day 1 (use of indomethacin is excluded)
  • If using methotrexate (MTX), sulfasalazine, hydroxychloroquine, chloroquine, or bucillamine, should have started treatment at least 3 months prior to Day 1, have no serious toxic side effects attributable to these agents, and be on a stable dose for at least 4 weeks prior to Day 1 and remain so during the entire duration of the study. If using MTX, the recommended doses are within the range of 7.5 mg to 25 mg oral or subcutaneous weekly. If currently not using MTX, sulfasalazine, hydroxychloroquine, chloroquine, or bucillamine, must have not received these agents for at least 4 weeks prior to Day 1.
  • If using oral corticosteroids, must be on a stable dose equivalent to ≤ 10 mg/day of prednisone for at least 2 weeks prior to Day 1. If currently not using oral corticosteroids, the patient must have not received oral corticosteroids for at least 2 weeks prior to screening

Exclusion Criteria:

  • Have received anti-tumor necrosis factor (TNF) agents (eg, infliximab, golimumab, adalimumab, etanercept, or certolizumab pegol) within 3 months of Day 1
  • Have a history of tocilizumab (anti-IL-6 receptor) or sirukumab use; have used B-cell depleting therapy (eg, rituximab) within 7 months of Day 1; have used anakinra within 4 weeks of Day 1; have used any other biologic therapy for the treatment of RA within 3 months of Day 1
  • Have received intra-articular (IA), intramuscular (IM), intravenous (IV), or topical corticosteroids, including adrenocorticotrophic hormone, during the 4 weeks prior to Day 1
  • Have received leflunomide within 24 months of Day 1 and have not undergone a drug elimination procedure, unless the M1 metabolite is measured and is undetectable
  • Have a history of cyclophosphamide or cytotoxic agent use; have received cyclosporine A, azathioprine, tacrolimus, mycophenolate mofetil, oral or parenteral gold, D-penicillamine, or IL-1ra (anakinra) within 4 weeks of Day 1; have received an investigational drug (including investigational vaccines) or used an investigational medical device within 3 months or 5 half-lives, whichever is longer, before Day 1
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01636557

Contacts
Contact: Use link at the bottom of the page to see if you qualify for an enrolling site (see list). If you still have questions: JNJ.CT@sylogent.com

Locations
Germany
Recruiting
Berlin, Germany
Recruiting
Munich, Germany
Korea, Republic of
Recruiting
Seoul, Korea, Republic of
Moldova, Republic of
Recruiting
Chisinau, Moldova, Republic of
South Africa
Recruiting
Bloemfontein, South Africa
Withdrawn
George, South Africa
Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
  More Information

Additional Information:
To learn how to participate in this trial please click here.  This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT01636557     History of Changes
Other Study ID Numbers: CR100842, CNTO136ARA1001
Study First Received: July 6, 2012
Last Updated: June 18, 2013
Health Authority: South Africa: Medicines Control Council

Keywords provided by Janssen Research & Development, LLC:
Rheumatoid arthritis
sirukumab
CNTO 136
CYP450 enzyme
anti-interleukin-6 monoclonal antibody

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Caffeine
Midazolam
Omeprazole
Vitamin K
Vitamins
Warfarin
Central Nervous System Stimulants
 Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Purinergic P1 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Adjuvants, Anesthesia
Anti-Anxiety Agents
Tranquilizing Agents
Central Nervous System Depressants

ClinicalTrials.gov processed this record on June 18, 2013