Arthritis, Rheumatoid
Conditions
Brief summary
Safety, pharmacokinetics, pharmacodynamics \[CD11b/CD18 (Mac-1) expression\] and efficacy.
Interventions
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
| Changes from baseline in tender joint count (TJC) | Pre-dose, up to day 14 after start of treatment | Bilateral assessment of twenty-eight joints by e.g., pressure, joint manipulation etc. |
| 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 | — |
| Number of withdrawals due to adverse events | Up to 4 weeks | — |
| Changes from baseline in swollen joint count (SJC) | Pre-dose, up to day 14 after start of treatment | Twenty-eight joints were bilaterally assessed whether they are swollen or not |
| 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 | Pre-dose, up to day 14 after start of treatment | Functional disability was measured using the disability section of the Health Assessment Questionnaire (HAQ) |
| 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 | — |
Outcome results
None listed