A Drug Interaction Study Between Tocilizumab, Methotrexate and Simvastatin on Patients With Rheumatoid Arthritis.

• Pharmacokinetic parameters for tocilizumab. [ Time Frame: Days 11, 22, 29 and 36. ] [ Designated as safety issue: No ]
• CRP, IL-6, sIL-6R changes [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
• AEs, laboratory parameters. [ Time Frame: Throughout study ] [ Designated as safety issue: No ]

This 2 arm study will investigate the pharmacokinetics of simvastatin and methotrexate in combination with tocilizumab to assess any potential drug interactions. Patients will be randomized to receive either tocilizumab (10mg/kg iv infusion on day 8) + methotrexate (10-25mg po /week) or tocilizumab + methotrexate + simvastatin (40mg po on days 1, 15 and 43). Blood samples will be taken for analysis at intervals up to day 44. The anticipated time on study treatment is <3 months, and the target sample size is <100 individuals.

• Drug: tocilizumab [RoActemra/Actemra]
  10mg/kg iv on day 8
• Drug: Methotrexate
  10-25mg po/week
• Drug: Simvastatin
  40mg po on days 1, 15 and 43

• Experimental: 1
  Interventions:

  • Drug: tocilizumab [RoActemra/Actemra]
  • Drug: Methotrexate
  • Drug: Simvastatin
• Active Comparator: 2
  Interventions:

  • Drug: tocilizumab [RoActemra/Actemra]
  • Drug: Methotrexate

Inclusion Criteria:

• adult patients, 18-75 years of age;
• rheumatoid arthritis for >=6 months;
• methotrexate for >=12 weeks prior to day 1 (stable at 10-25mg/week for 8 weeks).

Exclusion Criteria:

• history of, or current inflammatory joint disease or rheumatic autoimmune disease other than RA;
• concurrent treatment with any DMARD other than methotrexate;
• prior treatment with tocilizumab.