Arthritis, RheumatoidPhase 1NCT01636557
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
A Phase 1 study testing Sirukumab, Midazolam and Warfarin in people with Arthritis, Rheumatoid, run by Janssen Research & Development, LLC at 5 sites in 4 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Arthritis, Rheumatoid
- What is being tested?
- Sirukumab, Midazolam and Warfarin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 5 sitesin 4 countries
- Study dates
- 11 Oct 2012to 19 Oct 2013
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
5 sites in 4 countries.
5 sites in 4 countries
About this study
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
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.
Read the 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.
- Conditions
- Arthritis, Rheumatoid
- Being tested
- Sirukumab, Midazolam, Warfarin, Vitamin K, Omeprazole
- Keywords
- Rheumatoid arthritis, sirukumab, CNTO 136, CYP450 enzyme, anti-interleukin-6 monoclonal antibody
- Medical subject headings
- Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SirukumabDrug
Type=exact number, unit=mg, number=300, form=solution for injection, route=subcutaneous use, on Day 8
MidazolamDrug
Type=exact number, unit=mg/kg, number 0.03, form=commercially available form, route=oral use, on Days 1, 15, 29, and 50
WarfarinDrug
Type=exact number, unit=mg, number= 10, form=commercially available form, route=oral use, on Days 1, 15, 29, and 50
Vitamin KDrug
Type=exact number, unit=mg, number =10, form=commercially available form, route=oral use, on Days 1, 15, 29, and 50
OmeprazoleDrug
Type=exact number, unit=mg, number=20, form=commercially available form, route=oral use, on Days 1, 15, 29, and 50
CaffeineDrug
Type=exact number, unit=mg, number=100, form=commercially available form, route=oral use, on Days 1, 15, 29, and 50
| Study group | Role | What they receive |
|---|---|---|
| Sirukumab and 5-probe cocktail | Experimental | The 5-probe cocktail will consist of oral doses of midazolam, warfarin/vitamin K, omeprazole, and caffeine. Receives: Drug: Sirukumab; Drug: Midazolam; Drug: Warfarin; Drug: Vitamin K; Drug: Omeprazole; Drug: Caffeine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: Up to 54 days
Secondary outcomes (5)
Number of participants with adverse events
Measured: Up to 12 weeks
Clinical laboratory assessments
Blood and urine tests
Measured: Up to 12 weeks
Electrocardiograms (ECGs)
Measured: Up to 12 weeks
Vital signs evaluations
Measured: Up to 12 weeks
Physical examination
Measured: Up to 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jul 2012 (estimated)
- Study start11 Oct 2012
- Primary completion19 Oct 2013
- Study completion19 Oct 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Arthritis, RheumatoidStudies of the same condition, open and under way.
- More trials run by Janssen Research & Development, LLCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Janssen Research & Development, LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Janssen Research & Development, LLC Clinical Trial, Study director, Janssen Research & Development, LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01636557
- Sponsor's protocol ID
- CR100842
- Other IDs
- CNTO136ARA1001, 2011-001704-35
- Status last verified
- Mar 2017
- First submitted
- 6 Jul 2012
- Last updated
- 7 Mar 2017
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01636557
- Acronym / sponsor ID
- CR100842
- Conditions
- Arthritis, Rheumatoid
- Keywords
- Rheumatoid arthritis, sirukumab, CNTO 136, CYP450 enzyme, anti-interleukin-6 monoclonal antibody
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Janssen Research & Development, LLCIndustry (pharma, biotech, devices)
- Study start
- 11 Oct 2012 (actual)
- Primary completion
- 19 Oct 2013 (actual)
- Study completion
- 19 Oct 2013 (actual)
- First posted
- 10 Jul 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Sirukumab and 5-probe cocktail | Experimental | Drug: Sirukumab, Drug: Midazolam, Drug: Warfarin, Drug: Vitamin K, Drug: Omeprazole, Drug: CaffeineThe 5-probe cocktail will consist of oral doses of midazolam, warfarin/vitamin K, omeprazole, and caffeine. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SirukumabType=exact number, unit=mg, number=300, form=solution for injection, route=subcutaneous use, on Day 8 | Drug | Sirukumab and 5-probe cocktail |
| MidazolamType=exact number, unit=mg/kg, number 0.03, form=commercially available form, route=oral use, on Days 1, 15, 29, and 50 | Drug | Sirukumab and 5-probe cocktail |
| WarfarinType=exact number, unit=mg, number= 10, form=commercially available form, route=oral use, on Days 1, 15, 29, and 50 | Drug | Sirukumab and 5-probe cocktail |
| Vitamin KType=exact number, unit=mg, number =10, form=commercially available form, route=oral use, on Days 1, 15, 29, and 50 | Drug | Sirukumab and 5-probe cocktail |
| OmeprazoleType=exact number, unit=mg, number=20, form=commercially available form, route=oral use, on Days 1, 15, 29, and 50 | Drug | Sirukumab and 5-probe cocktail |
| CaffeineType=exact number, unit=mg, number=100, form=commercially available form, route=oral use, on Days 1, 15, 29, and 50 | Drug | Sirukumab and 5-probe cocktail |
Primary outcome
Pharmacokinetics of midazolam, S-warfarin, omeprazole, and caffeine
Time frame: Up to 54 days
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).
5 secondary outcomes
Number of participants with adverse events
Time frame: Up to 12 weeks
Clinical laboratory assessments
Time frame: Up to 12 weeks
Electrocardiograms (ECGs)
Time frame: Up to 12 weeks
Vital signs evaluations
Time frame: Up to 12 weeks
Physical examination
Time frame: Up to 12 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Mar 2017.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Janssen Research & Development, LLC Clinical Trial study director
Janssen Research & Development, LLC
5 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Sirukumab, Midazolam and Warfarin in people with Arthritis, Rheumatoid, run by Janssen Research & Development, LLC at 5 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Germany, Moldova, South Africa, South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pharmacokinetics of midazolam, S-warfarin, omeprazole, and caffeine (time frame: Up to 54 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Mar 2017.