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

Phase 1

Completed

• Conditions: Arthritis, Rheumatoid
• Interventions: Drug: High dose of BIIL 284 BS tablets; Drug: Low dose of BIIL 284 BS tablets; Drug: Placebo

• Registration Number: NCT02247375
• Lead Sponsor: Boehringer Ingelheim

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Study Start: 2000-01
• Primary Completion: 2000-05
• Status Verified: 2014-09
• Study First Submitted: 2014-09-19
• Study First Submitted QC: 2014-09-23
• Last Update Submitted: 2014-09-23
• Study First Posted: 2014-09-25
• Last Update Posted: 2014-09-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 26

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
High dose of BIIL 284 BS	High dose of BIIL 284 BS tablets	-
Low dose of BIIL 284 BS	Low dose of BIIL 284 BS tablets	-
Placebo	Placebo	-

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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
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
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.
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
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