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

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

Official Title
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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

Conditions
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Arthritis, Rheumatoid

Intervention / Treatment
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* Drug: Low dose of BIIL 284 BS tablets
* Drug: High dose of BIIL 284 BS tablets
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low dose of BIIL 284 BS<br> | Drug: Low dose of BIIL 284 BS tablets<br> <br> |
| Experimental: High dose of BIIL 284 BS<br> | Drug: High dose of BIIL 284 BS tablets<br> <br> |
| Placebo Comparator: Placebo<br> | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes from baseline in Mac-1 expression |  | Pre-dose, up to day 14 after start of treatment | 
| Plasma concentrations of BIIL 284 BS, BIIL 260 BS, BIIL 315 ZW and BIIL 304 ZW |  | Pre-dose, up to day 14 after start of treatment | 
| Maximum concentration of the analyte in plasma (Cmax) |  | Pre-dose, up to day 14 after start of treatment | 
| Trough concentration of the analyte in plasma shortly before drug administration in a steady state dosing interval (Cpre,ss) |  | Pre-dose, up to day 14 after start of treatment | 
| Time to reach the maximum concentration of the analyte in plasma (tmax) |  | Pre-dose, up to day 14 after start of treatment | 
| Area under the concentration-time curve of the analyte in plasma (AUC) |  | Pre-dose, up to day 14 after start of treatment | 
| Number of patients with adverse events |  | Up to 4 weeks | 
| Global assessment of tolerability by the patient on a 4-point scale |  | Up to 14 days after start of treatment | 
| Global assessment of tolerability by investigator on a 4-point scale |  | Up to 14 days after start of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes from baseline in tender joint count (TJC) | Bilateral assessment of twenty-eight joints by e.g., pressure, joint manipulation etc. | Pre-dose, up to day 14 after start of treatment | 
| Changes from baseline in swollen joint count (SJC) | Twenty-eight joints were bilaterally assessed whether they are swollen or not | Pre-dose, up to day 14 after start of treatment | 
| Changes from baseline in patient's current pain level assessment by visual analogue scale (VAS) |  | Pre-dose, up to day 14 after start of treatment | 
| Changes from baseline in patient's global assessment of disease activity by VAS |  | Pre-dose, up to day 14 after start of treatment | 
| Global assessment of disease activity by investigator on a 5-point scale |  | Up to 14 days after start of treatment | 
| Changes from baseline for patient's assessment of physical function | Functional disability was measured using the disability section of the Health Assessment Questionnaire (HAQ) | Pre-dose, up to day 14 after start of treatment | 
| Changes from baseline in erythrocyte sedimentation rate (ESR) |  | Pre-dose, up to day 14 after start of treatment | 
| Changes from baseline in C-reactive protein (CRP) |  | Pre-dose, up to day 14 after start of treatment | 
| Changes from baseline in american college of rheumatology (ACR) 20 score |  | Pre-dose, up to day 14 after start of treatment | 
| Changes from baseline in disease activity score (DAS) |  | Pre-dose, up to day 14 after start of treatment | 
| Global efficacy assessment by the patient on a 4-point scale |  | Up to 14 days after start of treatment | 
| Number of withdrawals due to adverse events |  | Up to 4 weeks | 
| Number of patients with clinically significant findings in laboratory adverse events |  | Up to 4 weeks | 
| Number of patients with clinically significant findings in vital signs (blood pressure, pulse rate) |  | Up to 4 weeks |