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

Arthritis, Rheumatoid Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02247375
• Other study ID #: 543.14
• Status: Completed
• Phase: Phase 1
• First received: September 19, 2014
• Last updated: September 23, 2014
• Start date: January 2000

Study information

• Verified date: September 2014
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 26
• Est. primary completion date: May 2000
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid

Intervention

Drug:
• Low dose of BIIL 284 BS tablets

• High dose of BIIL 284 BS tablets

• Placebo

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes from baseline in Mac-1 expression		Pre-dose, up to day 14 after start of treatment	No
Primary	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	No
Primary	Maximum concentration of the analyte in plasma (Cmax)		Pre-dose, up to day 14 after start of treatment	No
Primary	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	No
Primary	Time to reach the maximum concentration of the analyte in plasma (tmax)		Pre-dose, up to day 14 after start of treatment	No
Primary	Area under the concentration-time curve of the analyte in plasma (AUC)		Pre-dose, up to day 14 after start of treatment	No
Primary	Number of patients with adverse events		Up to 4 weeks	No
Primary	Global assessment of tolerability by the patient on a 4-point scale		Up to 14 days after start of treatment	No
Primary	Global assessment of tolerability by investigator on a 4-point scale		Up to 14 days after start of treatment	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	Changes from baseline in patient's global assessment of disease activity by VAS		Pre-dose, up to day 14 after start of treatment	No
Secondary	Global assessment of disease activity by investigator on a 5-point scale		Up to 14 days after start of treatment	No
Secondary	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	No
Secondary	Changes from baseline in erythrocyte sedimentation rate (ESR)		Pre-dose, up to day 14 after start of treatment	No
Secondary	Changes from baseline in C-reactive protein (CRP)		Pre-dose, up to day 14 after start of treatment	No
Secondary	Changes from baseline in american college of rheumatology (ACR) 20 score		Pre-dose, up to day 14 after start of treatment	No
Secondary	Changes from baseline in disease activity score (DAS)		Pre-dose, up to day 14 after start of treatment	No
Secondary	Global efficacy assessment by the patient on a 4-point scale		Up to 14 days after start of treatment	No
Secondary	Number of withdrawals due to adverse events		Up to 4 weeks	No
Secondary	Number of patients with clinically significant findings in laboratory adverse events		Up to 4 weeks	No
Secondary	Number of patients with clinically significant findings in vital signs (blood pressure, pulse rate)		Up to 4 weeks	No

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