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

Pulmonary Disease, Chronic Obstructive Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02249247
• Other study ID #: 543.17
• Status: Completed
• Phase: Phase 2
• First received: September 23, 2014
• Last updated: September 25, 2014
• Start date: April 2001

Study information

• Verified date: September 2014
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: South Africa: Medicines Control CouncilGermany: Federal Institute for Drugs and Medical DevicesUnited States: Food and Drug AdministrationNew Zealand: Ministry of HealthAustralia: National Health and Medical Research CouncilAustria: Agency for Health and Food SafetyBelgium: Federal Agency for Medicines and Health Products, FAMHPFrance: Agence Nationale de Sécurité du Médicament et des produits de santéIreland: Ministry of HealthItaly: The Italian Medicines AgencyNetherlands: Medicines Evaluation Board (MEB)United Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial Summary

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)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 577
• Est. primary completion date: August 2002
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years and older

Eligibility

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 Design

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

Related Conditions & MeSH terms

• Chronic Disease
• Lung Diseases
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• Low dose of BIIL 284 BS tablets

• Medium 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 in exercise endurance	evaluated by constant work load test	Pre-dose, up to 12 weeks after start of treatment	No
Secondary	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	No
Secondary	Changes in forced expiratory volume in one second (FEV1)	assessed by spirometry	Pre-dose, up to 12 weeks after start of treatment	No
Secondary	Changes in forced vital capacity (FVC)	assessed by spirometry	Pre-dose, up to 12 weeks after start of treatment	No
Secondary	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	No
Secondary	Changes in inspiratory capacity (IC)	assessed by spirometry	Pre-dose, up to 12 weeks after start of treatment	No
Secondary	Changes in slow vital capacity (SVC)	assessed by spirometry	Pre-dose, up to 12 weeks after start of treatment	No
Secondary	Change in thoracic gas volume	assessed by body plethysmography	Pre-dose, up to 12 weeks after start of treatment	No
Secondary	Changes in total lung capacity	assessed by body plethysmography	Pre-dose, up to 12 weeks after start of treatment	No
Secondary	Changes in residual volume	assessed by body plethysmography	Pre-dose, up to 12 weeks after start of treatment	No
Secondary	Changes in specific airway conductance	assessed by body plethysmography	Pre-dose, up to 12 weeks after start of treatment	No
Secondary	Changes in Mahler dyspnoea questionnaire	Baseline dyspnoea index / transitional dyspnoea index (BDI/TDI)	Pre-dose, up to 12 weeks after start of treatment	No
Secondary	Changes in chronic respiratory disease questionnaire (CRDQ)		Pre-dose, up to 12 weeks after start of treatment	No
Secondary	Changes in carbon monoxide diffusing capacity (DLco)		Pre-dose, up to 12 weeks after start of treatment	No
Secondary	Changes in diffusing capacity of carbon monoxide corrected for alveolar volume (DLco/VA)		Pre-dose, up to 12 weeks after start of treatment	No
Secondary	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	No
Secondary	Changes in 24-hours spontaneous sputum wet weight		Pre-dose, up 12 weeks after start of treatment	No
Secondary	Changes in oxygen saturation during constant work load test	assessed by pulse oximetry	Pre-dose, up to 12 weeks after start of treatment	No
Secondary	Changes in global evaluation assessed by investigator on a 4-point scale		Pre-dose, up to 14 weeks after start of treatment	No
Secondary	Clinically relevant changes in vital signs (pulse rate, blood pressure)		Pre-dose, up to 14 weeks after start of treatment	No
Secondary	Clinically relevant changes in ECG		Pre-dose, up to 14 weeks after start of treatment	No
Secondary	Clinically relevant changes in laboratory tests		Pre-dose, up to 14 weeks after start of treatment	No
Secondary	Number of patients with adverse events		Up to 17 weeks	No
Secondary	Number of patients with acute COPD exacerbations		Up to 17 weeks	No

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