Effect of Treatment With BIIL 284 BS on Exercise Endurance in Patients With Chronic Obstructive Pulmonary Disease

Effect of 12-week Treatment of 5, 25 or 75 mg BIIL 284 BS on Exercise Endurance in Patients With Chronic Obstructive Pulmonary Disease (Double-blind, Double Dummy, Placebo-controlled, Randomized, Parallel Group, Dose Ranging Study)

Study to investigate the effect of 12-week treatment with three doses (5, 25 and 75 mg) BIIL 284 BS on exercise endurance, lung function, quality of life, spontaneous sputum and safety in patients with chronic obstructive pulmonary disease (COPD)

Study Overview

• Status: Completed
• Conditions: Pulmonary Disease, Chronic Obstructive
• Intervention / Treatment: Drug: Placebo; Drug: Low dose of BIIL 284 BS tablets; Drug: Medium dose of BIIL 284 BS tablets; Drug: High dose of BIIL 284 BS tablets

• Study Type: Interventional
• Enrollment (Actual): 577
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• A diagnosis of COPD as defined by the American Thoracic Society (ATS) criteria. Patients had to have relatively stable airway obstruction with a FEV1 ≥ 20 % and ≤ 70 % of predicted value and FEV1/ FVC ≤ 70 % at screening Visit 1. Predicted normal values were based on the guidelines for standardised lung function testing of the European Community for Steel and Coal (ECSC) for patients of the Caucasian race and on the predicted equations for patients belonging to the Black race. Patients had to have lung hyperinflation as demonstrated by thoracic gas volume box (TGVbox) ≥ 100 % of predicted value (same as predicted value for functional residual capacity (FRC) measured by body plethysmography)

• Males or females aged 40 years or older. Female patients of childbearing potential could not participate in this study. Female patients had to be either:

  • surgically sterilised by hysterectomy or bilateral tubal ligation, or
  • post-menopausal for at least two years
• A smoking history of more than ten pack-years (p.y.). A p.y. was defined as the equivalent of smoking one pack of 20 cigarettes per day for a year
• Patients had to be able to perform pulmonary function testings (PFTs), exercise endurance test not terminated due to leg discomfort alone or other restrictions diseases (e.g. claudicatio intermittens, etc.) only and maintain records during the study period as required in the protocol
• All patients had to sign both informed consent forms (one on specific study procedures, one related to DNA derived determinations) prior to participation in the trial i.e., prior to pre-study washout of their usual pulmonary medications if they agreed to participate in both portions of the trial. The patient was not obligated to participate in the DNA collection portion of the trial

Exclusion Criteria:

• Clinical and/or radiographic evidence and/or antibiotic treatment of an upper or lower respiratory tract infection within the previous four weeks or during the screening period of this study
• Significant diseases other than COPD were excluded. A significant disease was defined as a disease which in the opinion of the investigator could either put the patient at risk because of participation in the study or a disease which could influence the results of the study or the patient's ability to participate in the study. Patients with inflammatory diseases, e.g., Rheumatoid Arthritis (RA), osteoarthritis, and those with autoimmune diseases were excluded
• Clinically significant abnormal baseline haematology, liver function, blood chemistry or urinalysis. If the abnormality defined a disease listed as an exclusion criterion the patient was excluded
• A recent history (i.e., within six months) of myocardial infarction
• A recent history (i.e., within three months) of refractory heart failure or unstable arrhythmia requiring treatment
• Patients with known tuberculosis
• A history of cancer within the last five years. Patients with treated basal cell carcinoma or cutaneous squamous cell carcinoma were allowed
• A history of life-threatening airway obstruction or a history of cystic fibrosis
• Previous thoracotomy with pulmonary resection. Patients with a history of a thoracotomy without pulmonary resection were evaluated as per exclusion criterion No. 2
• A change in pulmonary therapy, including rehabilitation therapy, within the four weeks prior to the first screening Visit (Visit 1) in order to control the patient's COPD
• A history of asthma or a total blood eosinophil count ≥ 600/mm3. A repeat eosinophil count was not conducted in these patients
• A history (within the past five years) of and/or current alcohol abuse and/or drug abuse
• Use of an investigational drug within one month or six half lives (which ever is greater) of the first Screening Visit (Visit 1)
• Patients requiring oxygen therapy 24 hours a day or requiring oxygen during exercise. Patients that desaturated during exercise were only excluded upon medical judgement of the investigator

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo
Experimental: Low dose of BIIL 284 BS	Drug: Low dose of BIIL 284 BS tablets
Experimental: Medium dose of BIIL 284 BS	Drug: Medium dose of BIIL 284 BS tablets
Experimental: High dose of BIIL 284 BS	Drug: High dose of BIIL 284 BS tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in exercise endurance	evaluated by constant work load test	Pre-dose, up to 12 weeks after start of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in breathlessness during constant work load test	measured by Modified Borg scale: Dyspnea score, leg discomfort	Week 4 and week 12 weeks after start of treatment
Changes in forced expiratory volume in one second (FEV1)	assessed by spirometry	Pre-dose, up to 12 weeks after start of treatment
Changes in forced vital capacity (FVC)	assessed by spirometry	Pre-dose, up to 12 weeks after start of treatment
Changes in forced expiratory flow at 25%-75% of FVC (FEF25-75%)	assessed by spirometry	Pre-dose, up to 12 weeks after start of treatment
Changes in inspiratory capacity (IC)	assessed by spirometry	Pre-dose, up to 12 weeks after start of treatment
Changes in slow vital capacity (SVC)	assessed by spirometry	Pre-dose, up to 12 weeks after start of treatment
Change in thoracic gas volume	assessed by body plethysmography	Pre-dose, up to 12 weeks after start of treatment
Changes in total lung capacity	assessed by body plethysmography	Pre-dose, up to 12 weeks after start of treatment
Changes in residual volume	assessed by body plethysmography	Pre-dose, up to 12 weeks after start of treatment
Changes in specific airway conductance	assessed by body plethysmography	Pre-dose, up to 12 weeks after start of treatment
Changes in Mahler dyspnoea questionnaire	Baseline dyspnoea index / transitional dyspnoea index (BDI/TDI)	Pre-dose, up to 12 weeks after start of treatment
Changes in chronic respiratory disease questionnaire (CRDQ)		Pre-dose, up to 12 weeks after start of treatment
Changes in carbon monoxide diffusing capacity (DLco)		Pre-dose, up to 12 weeks after start of treatment
Changes in diffusing capacity of carbon monoxide corrected for alveolar volume (DLco/VA)		Pre-dose, up to 12 weeks after start of treatment
Changes in peak expiratory flow rate (PEFR) daily patient record	assessed a.m. and p.m. in daily patient record	Pre-dose, up to 14 weeks after start of treatment
Changes in 24-hours spontaneous sputum wet weight		Pre-dose, up 12 weeks after start of treatment
Changes in oxygen saturation during constant work load test	assessed by pulse oximetry	Pre-dose, up to 12 weeks after start of treatment
Changes in global evaluation assessed by investigator on a 4-point scale		Pre-dose, up to 14 weeks after start of treatment
Clinically relevant changes in vital signs (pulse rate, blood pressure)		Pre-dose, up to 14 weeks after start of treatment
Clinically relevant changes in ECG		Pre-dose, up to 14 weeks after start of treatment
Clinically relevant changes in laboratory tests		Pre-dose, up to 14 weeks after start of treatment
Number of patients with adverse events		Up to 17 weeks
Number of patients with acute COPD exacerbations		Up to 17 weeks

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: April 1, 2001
• Primary Completion (Actual): August 1, 2002

Study Registration Dates

• First Submitted: September 23, 2014
• First Submitted That Met QC Criteria: September 23, 2014
• First Posted (Estimate): September 25, 2014

Study Record Updates

• Last Update Posted (Estimate): September 26, 2014
• Last Update Submitted That Met QC Criteria: September 25, 2014
• Last Verified: September 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: 543.17