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

NCT01636557 | Completed Phase 1

• 3 other identifiers: CR100842CNTO136ARA10012011-001704-35
• Study Type: interventional
• Target: 12
• Locations: 4 countries
• Sites: 5

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.

Conditions

Arthritis, Rheumatoid

Keywords

Rheumatoid arthritis; sirukumab; CNTO 136; CYP450 enzyme; anti-interleukin-6 monoclonal antibody

Outcome Measures

Primary Outcomes (1)

• 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).

  Up to 54 days

Secondary Outcomes (5)

• Number of participants with adverse events

  Up to 12 weeks

• Clinical laboratory assessments

  Up to 12 weeks

• Electrocardiograms (ECGs)

  Up to 12 weeks

• Vital signs evaluations

  Up to 12 weeks

• Physical examination

  Up to 12 weeks

Study Arms (1)

Sirukumab and 5-probe cocktail

EXPERIMENTAL

The 5-probe cocktail will consist of oral doses of midazolam, warfarin/vitamin K, omeprazole, and caffeine.

Drug: Sirukumab; Drug: Midazolam; Drug: Warfarin; Drug: Vitamin K; Drug: Omeprazole; Drug: Caffeine

Interventions

Sirukumab DRUG

Type=exact number, unit=mg, number=300, form=solution for injection, route=subcutaneous use, on Day 8

Sirukumab and 5-probe cocktail

Midazolam DRUG

Type=exact number, unit=mg/kg, number 0.03, form=commercially available form, route=oral use, on Days 1, 15, 29, and 50

Sirukumab and 5-probe cocktail

Warfarin DRUG

Type=exact number, unit=mg, number= 10, form=commercially available form, route=oral use, on Days 1, 15, 29, and 50

Sirukumab and 5-probe cocktail

Vitamin K DRUG

Type=exact number, unit=mg, number =10, form=commercially available form, route=oral use, on Days 1, 15, 29, and 50

Sirukumab and 5-probe cocktail

Omeprazole DRUG

Type=exact number, unit=mg, number=20, form=commercially available form, route=oral use, on Days 1, 15, 29, and 50

Sirukumab and 5-probe cocktail

Caffeine DRUG

Type=exact number, unit=mg, number=100, form=commercially available form, route=oral use, on Days 1, 15, 29, and 50

Sirukumab and 5-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 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (5)

Unknown Facility

Berlin, Germany

Location

Unknown Facility

Munich, Germany

Location

Unknown Facility

Chisinau, Moldova

Location

Unknown Facility

Bloemfontein, South Africa

Location

Unknown Facility

Seoul, South Korea

Location

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

sirukumab; Midazolam; Warfarin; Vitamin K; Omeprazole; Caffeine

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System 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; Naphthoquinones; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Phytol; Diterpenes; Terpenes; Polycyclic Compounds; 2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Pyridines; Benzimidazoles; Xanthines; Alkaloids; 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: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 6, 2012
• First Posted: July 10, 2012
• Study Start: October 11, 2012
• Primary Completion: October 19, 2013
• Study Completion: October 19, 2013
• Last Updated: March 7, 2017

Record last verified: 2017-03

Locations

MO (1); ZA (1); DE (2); KR (1)