Efficacy and Safety of BIIL 284 BS in Adult Patients With Active Rheumatoid Arthritis

Arthritis, Rheumatoid Clinical Trial

Official title:

Three Month, Randomised, Double-blind, Double-dummy, Placebo-controlled, Multiple Dose-range Study of the Efficacy and Safety of BIIL 284 BS (5, 25 and 75 mg p.o. Once Daily) in Adult Patients With Active Rheumatoid Arthritis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02251210
• Other study ID #: 543.27
• Status: Completed
• Phase: Phase 2
• First received: September 25, 2014
• Last updated: September 25, 2014
• Start date: May 2001

Study information

• Verified date: September 2014
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Agence Nationale de Sécurité du Médicament et des produits de santéGermany: Federal Institute for Drugs and Medical DevicesItaly: Ministry of HealthSpain: Ministry of HealthBelgium: Federal Agency for Medicines and Health Products, FAMHPCanada: Health Canada
• Study type: Interventional

Clinical Trial Summary

To investigate efficacy and safety of 3 doses of BIIL 284 BS in active rheumatoid arthritis (RA) and determine the dose with most positive efficacy / safety ratio. Pharmacokinetic profile will be also obtained.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 404
• Est. primary completion date: November 2002
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• Patients of >=18 and <= 70 years of age

• Patients suffering from rheumatoid arthritis as defined by the American Rheumatism Association (ARA) criteria revised 1987 and date of diagnosis >= 6 months. At least 4 of the following 7 criteria must be 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

• Symmetrical 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 prominence or extensor surfaces or in juxta-articular regions

• Serum rheumatoid factor positive

• X-ray changes typical of rheumatoid arthritis (erosions or unequivocal bony decalcification localized in or most marked adjacent to the involved joints)

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

• Active RA as defined at visit 2 by:

• Swollen joint count at least of 6 (of 28 joints examined) and

• Tender joint count at least of 8 (of 28 joints examined) and

• Patients must fulfil 2 out of the 3 following criteria:

• Patient's assessment of pain (VAS) >= 40 mm

• Investigator's global assessment of disease activity on a VAS >= 40 mm

• ESR >= 28 mm/h or CRP >= 20 mg/L

• Patient's written informed consent obtained at Visit 1 (screening) before enrolment in the study

Exclusion Criteria:

• Patient presenting or having a history of inflammatory rheumatic disease other than RA (e.g.: mixed connective tissue disease, systemic lupus erythematosus, seronegative spondyloarthropathy)

• Patients who have failed to more than 3 different disease-modifying antirheumatic drug (DMARDs) therapies previously due to lack of efficacy (in case of combined therapy each DMARDs used is counted as one)

• Patients with any other disease that could interfere with the evaluation of efficacy and safety

• Patients in treatment with any DMARDs / slow-acting anti-rheumatic drug (SAARDs) during the periods specified:

• 4 weeks before V2: Methotrexate, parenteral/oral gold, D-penicillamine, Sulphasalazine, antimalarials (e.g.:Chloroquine/Hydroxychloroquine), Azathioprine, Cyclosporine A, Alkylating agents (e.g.: Cyclophosphamide / Chlorambucil), Minocycline, Etanercept (Enbrel®), and Leflunomide (only if wash-out with Colestyramine has been done after leflunomide discontinuation)

• 3 months before Visit 2: Leflunomide if no wash- out with colestyramine has been done after leflunomide discontinuation, Infliximab (Remicade®), any other biological compound.

• Patient in treatment with oral corticosteroids at a dose higher than 10 mg/day or 0.2 mg/Kg/day (prednisone equivalent) whichever is lower, during the 4 weeks prior to Visit 2, change in the treatment with oral corticosteroids during the 4 weeks prior to Visit 2 or intended change during the trial

• Patients in treatment with any parenteral (intravenous, intramuscular or intraarticular) treatment with corticosteroids during the 4 weeks prior to Visit 2 or their intended use during the trial.

• Change in treatment with non-steroidal anti-inflammatory drugs (NSAIDs) during the 2 weeks prior to Visit 2 or any intended change during the trial.

• Synovectomy, and/or surgical treatment for RA in the previous 3 months prior to visit 2 or intended indication during the trial.

• Synoviorthesis in the previous 4 weeks prior to Visit 2 or intended indication during the trial.

• Patients in treatment with any other leukotriene inhibitors such as montelukast or zafirlukast 4 weeks prior to Visit 2 or intended use during the trial.

• Initiation of physiotherapy during the 2 weeks before V2, or intended change during the trial

• Patients with history of cardiovascular, renal, neurologic, psychiatric, liver, gastrointestinal (including lactose intolerance ), immunologic or endocrine dysfunction if they are clinically significant.

• Patients with any other known condition or circumstance, which would in the investigator's opinion, prevents compliance or completion of the study

• Patients with history of cancer within the past 5 years, excluding treated basal cell carcinoma

• Patients with chronic infection or acute infections during the 4 weeks before visit 1

• Patients with known positive serology for hepatitis B or C

• Patients with anticoagulant treatment (i.e. dicumarol or derivatives, warfarin)

• Any of the following abnormal laboratory parameters at Visit 2:

• Impaired hepatic function, defined by serum levels of either Aspartate Aminotransferase (AST)(SGOT), Alanine Aminotransferase (ALT) (SGPT), alkaline phosphatase or bilirubin > 2 x upper limit of normal (ULN)

• Impaired renal function, defined by serum creatinine > 133 mmol/L (1.5 mg/dl)

• Hemoglobin values < 10 g/dl

• White blood cell count <= 3.500 cells/mm3

• Platelet count of less than 120.000/mm3

• Severe hypoproteinemia (e.g. in case of severe liver disease or nephrotic syndrome) with albumin < 3.0 g/dl

• Patients with any other abnormal, clinically relevant laboratory values not related to RA

• Patients participating in another clinical trial during the 3 months prior to visit 2

• Previous participation in the randomised period of this study

• Patients with a significant history and/or active alcohol or drug abuse Significant is defined as that which in the opinion of the investigator may either put the patient at risk because of participation in the study or may influence the results of the study or the patient's ability to participate in the study

• Pregnancy (to be excluded by pregnancy test at visit 1) or breast feeding, and sexually active women with childbearing potential not using a medically approved method of contraception (i.e. oral contraceptives, intrauterine devices, or double-barrier) for at least one month before and throughout the study period

Study Design

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

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid

Intervention

Drug:
• BIIL 284 BS low dose

• BIIL 284 BS medium dose

• BIIL 284 BS high dose

• Placebo

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of patients achieving 20% improvement assessed by the American College of Rheumatology (ACR) criteria (ACR20)		3 months	No
Secondary	Percentage of patients achieving 50% improvement (ACR50)		3 months	No
Secondary	Number of withdrawals due to lack of efficacy		up to 3 months	No
Secondary	Number of swollen joints		up to 3 months	No
Secondary	Number of tender joints		up to 3 months	No
Secondary	Patient's assessment of pain on a visual analog scale (VAS)		up to 3 months	No
Secondary	Patient's global assessment of disease activity by VAS		up to 3 months	No
Secondary	Investigator's global assessment of disease activity by VAS		up to 3 months	No
Secondary	Patient's assessment of physical function	via Health Assessment Questionnaire (HAQ)	up to 3 months	No
Secondary	Change in erythrocyte sedimentation rate (ESR)		up to 3 months	No
Secondary	Change in C-reactive protein (CRP)		up to 3 months	No
Secondary	Change in Quality of Life	assessed by the SF-36 questionnaire	baseline, 3 months	No
Secondary	Change in Disease Activity Score (DAS 28)	Disease Activity Score in 28-joint count	baseline, up to 3 months	No
Secondary	Change in duration of morning stiffness		up to 3 months	No
Secondary	Consumption of rescue medication		up to 3 months	No
Secondary	Number of patients with adverse events		up to 3 months	No
Secondary	Number of withdrawals due to adverse events		up to 3 months	No
Secondary	Final global assessment of tolerability by investigator on a 4-point scale		3 months	No
Secondary	Patient's assessment of fatigue by VAS		up to 3 months	No
Secondary	Number of patients with clinically significant changes in laboratory findings		up to 3 months	No
Secondary	Number of patients with clinically significant changes in vital signs		up to 3 months	No
Secondary	Number of patients with clinically significant changes in 12-lead ECG		3 months	No

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