Pharmacokinetics, Safety and Efficacy of BIIL 284 BS in Patients With Rheumatoid Arthritis (RA)

A Double-blind, Randomized, Three Parallel Group Placebo-controlled Study to Investigate Pharmacokinetics, Effect on Expression of CD11b/CD18 (Mac-1), as Well as Safety and Efficacy of Two Oral Doses of BIIL 284 BS (Dosage: 25 mg Daily, 150 mg Daily) in Patients With Rheumatoid Arthritis Over Two Weeks

Safety, pharmacokinetics, pharmacodynamics [CD11b/CD18 (Mac-1) expression] and efficacy.

Inclusion Criteria:

• Male and female from 18 to 65 years of age

• Patients suffering from active rheumatoid arthritis as defined by the ARA criteria revised 1987

  --- At least 4 of the following 7 criteria must have been present:

  • morning stiffness in and around the joints lasting at least 1 hour before maximal improvement for at least 6 weeks
  • arthritis (soft tissue thickening or fluid - not bony overgrowth alone) of at least 3 joint areas for at least 6 weeks
  • arthritis of hand joints (at least one area swollen in a wrist, metacarpophalangeal (MCP) or proximal interphalangeal (PIP) joint) for at least 6 weeks
  • symmetric arthritis (observed by a physician) with simultaneous involvement of the joints on both sides of the body for at least 6 weeks
  • rheumatoid nodules (observed by a physician) over bony prominences or extensor surfaces or in juxta-articular regions
  • serum rheumatoid factor positive
  • x-ray changes typical of rheumatoid arthritis (erosions or unequivocal bony decalcification localised in or most marked adjacent to the involved joints)

• Patient belonging to the RA functional class I, II or III

• Patient's written informed consent

Exclusion Criteria:

• Pregnancy (to be excluded by pregnancy test) or breast feeding
• Women of childbearing potential not using adequate contraception
• Treatment with methotrexate in the previous month or intended use during the trial period
• Treatment with slow acting antirheumatic drugs (SAARDs)/disease-modifying antirheumatic drugs (DMARDs) other than parenteral gold, D-penicillamine, sulfasalazine, chloroquine / hydroxychloroquine corticosteroid during the last 2 months prior to study entry
• Treatment with more than one SAARD/DMARD and/or corticosteroid during the last 2 months prior to study entry
• Change in treatment with SAARDs/DMARDs during the last 2 months prior to study entry or intended change during the trial duration
• Change in treatment with corticosteroids during the last month prior to study entry or intended change during the trial duration
• Systemic treatment with corticosteroids at a dose higher than 10 mg/day or 0.2 mg/kg/day (prednisone equivalent), respectively (whichever is lower) during the last month prior to study entry or their intended use during the trial treatment period
• Change in treatment with non-steroidal anti-inflammatory drugs (NSAIDs) during the last month prior to study entry or intended change during the trial duration
• Treatment with EnbrelTM (etanercept) or experimental therapies during the last 3 months prior to study entry
• Synovectomy and/or surgical treatment for RA in the previous month or during the trial
• Clinical evidence of known severe cardiovascular, hepatic, renal, respiratory, metabolic, haematological, immunological, gastro-intestinal, hormonal or mental disorders
• Any other rheumatological or non-rheumatological disease that could interfere with the evaluation of efficacy and safety
• Patients with active malignant disease
• Patients with chronic or acute infections during the previous month
• Patients with abnormal, clinically relevant laboratory values not related to RA
• Participation in another clinical trial during this study or during the previous month
• Previous participation in this trial (i.e. having been allocated a randomized treatment number)
• Patient unable to comply with the protocol
• Patient with known drug abuse
• Patient with known alcohol abuse