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
Primary Purpose
Arthritis, Rheumatoid
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Sirukumab
Midazolam
Warfarin
Vitamin K
Omeprazole
Caffeine
Sponsored by
About this trial
This is an interventional basic science trial for Arthritis, Rheumatoid focused on measuring Rheumatoid arthritis, sirukumab, CNTO 136, CYP450 enzyme, anti-interleukin-6 monoclonal antibody
Eligibility 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
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Sirukumab and 5-probe cocktail
Arm Description
The 5-probe cocktail will consist of oral doses of midazolam, warfarin/vitamin K, omeprazole, and caffeine.
Outcomes
Primary Outcome Measures
Pharmacokinetics of midazolam, S-warfarin, omeprazole, and caffeine
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
Clinical laboratory assessments
Blood and urine tests
Electrocardiograms (ECGs)
Vital signs evaluations
Physical examination
Full Information
NCT ID
NCT01636557
First Posted
July 6, 2012
Last Updated
March 6, 2017
Sponsor
Janssen Research & Development, LLC
1. Study Identification
Unique Protocol Identification Number
NCT01636557
Brief Title
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
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
Study Type
Interventional
2. Study Status
Record Verification Date
March 2017
Overall Recruitment Status
Completed
Study Start Date
October 11, 2012 (Actual)
Primary Completion Date
October 19, 2013 (Actual)
Study Completion Date
October 19, 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Janssen Research & Development, LLC
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Arthritis, Rheumatoid
Keywords
Rheumatoid arthritis, sirukumab, CNTO 136, CYP450 enzyme, anti-interleukin-6 monoclonal antibody
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
12 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Sirukumab and 5-probe cocktail
Arm Type
Experimental
Arm Description
The 5-probe cocktail will consist of oral doses of midazolam, warfarin/vitamin K, omeprazole, and caffeine.
Intervention Type
Drug
Intervention Name(s)
Sirukumab
Intervention Description
Type=exact number, unit=mg, number=300, form=solution for injection, route=subcutaneous use, on Day 8
Intervention Type
Drug
Intervention Name(s)
Midazolam
Intervention Description
Type=exact number, unit=mg/kg, number 0.03, form=commercially available form, route=oral use, on Days 1, 15, 29, and 50
Intervention Type
Drug
Intervention Name(s)
Warfarin
Intervention Description
Type=exact number, unit=mg, number= 10, form=commercially available form, route=oral use, on Days 1, 15, 29, and 50
Intervention Type
Drug
Intervention Name(s)
Vitamin K
Intervention Description
Type=exact number, unit=mg, number =10, form=commercially available form, route=oral use, on Days 1, 15, 29, and 50
Intervention Type
Drug
Intervention Name(s)
Omeprazole
Intervention Description
Type=exact number, unit=mg, number=20, form=commercially available form, route=oral use, on Days 1, 15, 29, and 50
Intervention Type
Drug
Intervention Name(s)
Caffeine
Intervention Description
Type=exact number, unit=mg, number=100, form=commercially available form, route=oral use, on Days 1, 15, 29, and 50
Primary Outcome Measure Information:
Title
Pharmacokinetics of midazolam, S-warfarin, omeprazole, and caffeine
Description
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).
Time Frame
Up to 54 days
Secondary Outcome Measure Information:
Title
Number of participants with adverse events
Time Frame
Up to 12 weeks
Title
Clinical laboratory assessments
Description
Blood and urine tests
Time Frame
Up to 12 weeks
Title
Electrocardiograms (ECGs)
Time Frame
Up to 12 weeks
Title
Vital signs evaluations
Time Frame
Up to 12 weeks
Title
Physical examination
Time Frame
Up to 12 weeks
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 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
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
Berlin
Country
Germany
City
Munich
Country
Germany
City
Seoul
Country
Korea, Republic of
City
Chisinau
Country
Moldova, Republic of
City
Bloemfontein
Country
South Africa
12. IPD Sharing Statement
Learn more about this trial
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
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