Effect of Tiotropium on Exercise Tolerance in Patients With Chronic Obstructive Pulmonary Disease (COPD)
Primary Purpose
Pulmonary Disease, Chronic Obstructive
Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Tiotropium inhalation capsules
Placebo inhalation capsules
Sponsored by
About this trial
This is an interventional treatment trial for Pulmonary Disease, Chronic Obstructive
Eligibility Criteria
Inclusion Criteria:
All patients had to have a diagnosis of COPD. Patients had to meet the following spirometric and static lung volume criteria:
- Patients had to have relatively stable, mild (stage I according to the criteria of the American Thoracic Society (ATS); original trial protocol: moderate) to severe airway obstruction with an FEV1 less than or equal to 65% of predicted values. All patients had to have presence of lung hyperinflation as demonstrated by thoracic gas volume (TGV) / functional residual capacity (FRC) greater than or equal to 120% of predicted value as determined by body plethysmography at Visit 1 (day -15).
- Male or female patients ≥ 40 but ≤ 70 years old.
- Patients had to have a cigarette smoking history of more than 10 pack-years. A pack-year was defined as the equivalent of smoking one pack of cigarettes per day for a year.
- Patients had to be able to perform all specified procedures and maintain records during the study period as required in the protocol.
- Patients had to be able to inhale medication from the HandiHaler®.
- All patients had to sign an Informed Consent Form in accordance with Good Clinical Practice (GCP) and local legislative requirements prior to participation in the trial . i.e., prior to pre-study washout of their usual pulmonary medications.
Exclusion Criteria:
- Patients with significant diseases other than COPD were to be excluded. A significant disease was defined either as a disease, which in the opinion of the investigator might have put the patient at risk because of participation in the study or a disease, which might have influenced the results of the study or the patient's ability to participate in the study.
- Patients with clinically significant abnormal baseline hematology, blood chemistry or urinalysis. If the abnormality defined a disease listed as an exclusion criterion, the patient was to be excluded.
- All patients with a serum glutamic oxaloacetic transaminase (SGOT or AST) ≥ 1.5 of the upper limit of normal range (x ULN), serum glutamic pyruvic transaminase (SGPT or ALT) ≥ 1.5 x ULN, bilirubin ≥ 1.5 x ULN, or creatinine ≥ 1.5 x ULN were excluded regardless of the clinical condition. Repeat laboratory evaluation was not to be conducted in these subjects.
- Patients with a recent history (i.e., 1 year or less) of myocardial infarction.
- Patients with a recent history (i.e., 3 years or less) of heart failure, pulmonary edema, or patients with cardiac arrhythmia (with or without symptoms) or any contraindication to exercise as indicated in Protocol Appendix four (see Section 9.5.1 and Appendices 16.1.1.1 and 16.1.1.2).
- Patients with regular use of daytime oxygen therapy. (In centers with significantly decreased barometric pressure, exercise tests can be done with inhaled oxygen).
- Patients with known active tuberculosis.
- Patients with a history of cancer within the last 5 years. Patients with treated basal cell carcinoma were allowed.
- Patients with a history of life-threatening pulmonary obstruction or a history of cystic fibrosis or bronchiectasis.
- Patients who had undergone thoracotomy with pulmonary resection. Patients with a history of thoracotomy for other reason were to be evaluated as per exclusion criterion No. 1.
- Patients with upper respiratory tract infection in the past 6 weeks prior to the Screening visit (Visit 1, day -15) or during the run-in period.
- Patients with known hypersensitivity to anticholinergic drugs, lactose or any other components of the inhalation capsule delivery system.
- Patients with known symptomatic prostatic hypertrophy or bladder neck obstruction.
- Patients with known narrow-angle glaucoma.
- Patients with a history of asthma, allergic rhinitis or atopy or who have a total blood eosinophil count ≥ 600/mm3. A repeat eosinophil count was not to be conducted in these patients.
- Patients who were being treated with cromolyn sodium or nedocromil sodium had to stop these medications 1 month before Visit 1 (day -15).
- Patients who were being treated with antihistamines (H1 receptor antagonists) or antileukotrienes had to stop these medications 1 month before Visit 1 (day -15).
- Patients using oral corticosteroid medication at unstable doses (i.e., less than 6 weeks on a stable dose) or at a dose in excess of the equivalent of 10 mg of prednisone per day or 20 mg every other day.
- Pregnant or nursing women or women of childbearing potential not using a medically approved means of contraception (i.e., oral contraceptives, intrauterine devices, diaphragm or Norplant®).
- Patients with history or active alcohol or drug abuse.
- Patients who had taken an investigational drug within 1 month or 10 half lives (whichever was greater) prior to Screening visit (Visit 1, day -15).
- Limitation of exercise performance as a result of factors other than fatigue or exertional dyspnea such as arthritis in the leg, angina or claudication.
- Patients who participated in any rehabilitation program for COPD within 6 weeks prior to Visit 1 (day -15).
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Tiotropium
Placebo
Arm Description
Tiotropium inhalation capsules via HandiHaler
Placebo inhalation capsules via HandiHaler
Outcomes
Primary Outcome Measures
Evaluation of submaximal exercise tolerance (as measured by endurance time during a constant work rate exercise test to symptom limitation)
Secondary Outcome Measures
Endurance time after first dosing
Determination of breathlessness (dyspnea) during constant work rate exercise test as measured by the modified Borg Scale
Determination of leg discomfort during constant work rate exercise test as measured by the modified Borg Scale
Evaluation of dynamic lung hyperinflation during exercise
Evaluation of dynamic hyperinflation (DH) as negative change in inspiratory capacity (IC) from rest
Evaluation of static lung hyperinflation
Evaluation of TAV (Trapped air volume) at rest
Evaluation of slow vital capacity (SVC)
Evaluation of FEV1 (Forced expiratory volume in one second)
Evaluation of forced vital capacity (FVC)
Evaluation of forced expiratory flow rate between 25% and 75% of FVC which has been exhaled (FEF25-75%)
Evaluation of forced expiratory flow rate at 50% of FVC which has been exhaled (FEF50%)
Evaluation of forced expiratory flow rate at 75% of FVC which has been exhaled (FEF75%)
Evaluation of total lung capacity (TLC), airway resistance (Raw), and specific airway conductance (SGaw)
Evaluation of dyspnea using the Baseline Dyspnea Index (BDI) and Transition Dyspnoea Index (TDI)
Determination of arterial oxygen saturation (SaO2), oxygen consumption (VO2), tidal volume (VT), breathing frequency (F), and minute ventilation (VE)
Physicians Global Assessment
Evaluation of COPD symptom scores
Reason for stopping constant work rate exercise
Rescue medication use during test days
Rescue medication use as weekly mean for number of night-time puffs (Rescni,w), daytime puffs (Rescday,w) and total daily puffs (Resctot,w) of rescue medication
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02172300
Brief Title
Effect of Tiotropium on Exercise Tolerance in Patients With Chronic Obstructive Pulmonary Disease (COPD)
Official Title
Effect of Tiotropium on Exercise Tolerance and Static and Dynamic Lung Volumes in COPD Patients (A Randomized Double-Blind, Placebo Controlled, Parallel Group Study)
Study Type
Interventional
2. Study Status
Record Verification Date
June 2014
Overall Recruitment Status
Completed
Study Start Date
June 1999 (undefined)
Primary Completion Date
November 2000 (Actual)
Study Completion Date
undefined (undefined)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Boehringer Ingelheim
4. Oversight
5. Study Description
Brief Summary
Study to investigate whether tiotropium therapy can increase duration of steady-state exercise by decreasing dynamic and static lung hyperinflation in COPD patients.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pulmonary Disease, Chronic Obstructive
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
198 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Tiotropium
Arm Type
Experimental
Arm Description
Tiotropium inhalation capsules via HandiHaler
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo inhalation capsules via HandiHaler
Intervention Type
Drug
Intervention Name(s)
Tiotropium inhalation capsules
Intervention Type
Drug
Intervention Name(s)
Placebo inhalation capsules
Primary Outcome Measure Information:
Title
Evaluation of submaximal exercise tolerance (as measured by endurance time during a constant work rate exercise test to symptom limitation)
Time Frame
Day 42
Secondary Outcome Measure Information:
Title
Endurance time after first dosing
Time Frame
Day 0 and 21
Title
Determination of breathlessness (dyspnea) during constant work rate exercise test as measured by the modified Borg Scale
Time Frame
Day -10, -5, 0, 21 and 42
Title
Determination of leg discomfort during constant work rate exercise test as measured by the modified Borg Scale
Time Frame
Day -10, -5, 0, 21 and 42
Title
Evaluation of dynamic lung hyperinflation during exercise
Time Frame
Day -10, -5, 0, 21 and 42
Title
Evaluation of dynamic hyperinflation (DH) as negative change in inspiratory capacity (IC) from rest
Time Frame
Day -10, -5, 0, 21 and 42
Title
Evaluation of static lung hyperinflation
Time Frame
Day -10, -5, 0, 21 and 42
Title
Evaluation of TAV (Trapped air volume) at rest
Time Frame
Day -10, -5, 0, 21 and 42
Title
Evaluation of slow vital capacity (SVC)
Time Frame
Day -10, -5, 0, 21, 42 and 56
Title
Evaluation of FEV1 (Forced expiratory volume in one second)
Time Frame
Day -10, -5, 0, 21 and 42
Title
Evaluation of forced vital capacity (FVC)
Time Frame
Day -10, -5, 0, 21 and 42
Title
Evaluation of forced expiratory flow rate between 25% and 75% of FVC which has been exhaled (FEF25-75%)
Time Frame
Day -10, -5, 0, 21 and 42
Title
Evaluation of forced expiratory flow rate at 50% of FVC which has been exhaled (FEF50%)
Time Frame
Day -10, -5, 0, 21 and 42
Title
Evaluation of forced expiratory flow rate at 75% of FVC which has been exhaled (FEF75%)
Time Frame
Day -10, -5, 0, 21 and 42
Title
Evaluation of total lung capacity (TLC), airway resistance (Raw), and specific airway conductance (SGaw)
Time Frame
Day -10, -5, 0, 21 and 42
Title
Evaluation of dyspnea using the Baseline Dyspnea Index (BDI) and Transition Dyspnoea Index (TDI)
Time Frame
Day 0, 21 and 42
Title
Determination of arterial oxygen saturation (SaO2), oxygen consumption (VO2), tidal volume (VT), breathing frequency (F), and minute ventilation (VE)
Time Frame
Day -10, -5, 0, 21 and 42
Title
Physicians Global Assessment
Time Frame
Day 0 and 42
Title
Evaluation of COPD symptom scores
Time Frame
Day 0, 21 and 42
Title
Reason for stopping constant work rate exercise
Time Frame
Day -15, -10, -5, 0, 21 and 42
Title
Rescue medication use during test days
Time Frame
Day -15, -10, -5, 0, 21 and 42
Title
Rescue medication use as weekly mean for number of night-time puffs (Rescni,w), daytime puffs (Rescday,w) and total daily puffs (Resctot,w) of rescue medication
Time Frame
until week 6
10. Eligibility
Sex
All
Minimum Age & Unit of Time
40 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
All patients had to have a diagnosis of COPD. Patients had to meet the following spirometric and static lung volume criteria:
Patients had to have relatively stable, mild (stage I according to the criteria of the American Thoracic Society (ATS); original trial protocol: moderate) to severe airway obstruction with an FEV1 less than or equal to 65% of predicted values. All patients had to have presence of lung hyperinflation as demonstrated by thoracic gas volume (TGV) / functional residual capacity (FRC) greater than or equal to 120% of predicted value as determined by body plethysmography at Visit 1 (day -15).
Male or female patients ≥ 40 but ≤ 70 years old.
Patients had to have a cigarette smoking history of more than 10 pack-years. A pack-year was defined as the equivalent of smoking one pack of cigarettes per day for a year.
Patients had to be able to perform all specified procedures and maintain records during the study period as required in the protocol.
Patients had to be able to inhale medication from the HandiHaler®.
All patients had to sign an Informed Consent Form in accordance with Good Clinical Practice (GCP) and local legislative requirements prior to participation in the trial . i.e., prior to pre-study washout of their usual pulmonary medications.
Exclusion Criteria:
Patients with significant diseases other than COPD were to be excluded. A significant disease was defined either as a disease, which in the opinion of the investigator might have put the patient at risk because of participation in the study or a disease, which might have influenced the results of the study or the patient's ability to participate in the study.
Patients with clinically significant abnormal baseline hematology, blood chemistry or urinalysis. If the abnormality defined a disease listed as an exclusion criterion, the patient was to be excluded.
All patients with a serum glutamic oxaloacetic transaminase (SGOT or AST) ≥ 1.5 of the upper limit of normal range (x ULN), serum glutamic pyruvic transaminase (SGPT or ALT) ≥ 1.5 x ULN, bilirubin ≥ 1.5 x ULN, or creatinine ≥ 1.5 x ULN were excluded regardless of the clinical condition. Repeat laboratory evaluation was not to be conducted in these subjects.
Patients with a recent history (i.e., 1 year or less) of myocardial infarction.
Patients with a recent history (i.e., 3 years or less) of heart failure, pulmonary edema, or patients with cardiac arrhythmia (with or without symptoms) or any contraindication to exercise as indicated in Protocol Appendix four (see Section 9.5.1 and Appendices 16.1.1.1 and 16.1.1.2).
Patients with regular use of daytime oxygen therapy. (In centers with significantly decreased barometric pressure, exercise tests can be done with inhaled oxygen).
Patients with known active tuberculosis.
Patients with a history of cancer within the last 5 years. Patients with treated basal cell carcinoma were allowed.
Patients with a history of life-threatening pulmonary obstruction or a history of cystic fibrosis or bronchiectasis.
Patients who had undergone thoracotomy with pulmonary resection. Patients with a history of thoracotomy for other reason were to be evaluated as per exclusion criterion No. 1.
Patients with upper respiratory tract infection in the past 6 weeks prior to the Screening visit (Visit 1, day -15) or during the run-in period.
Patients with known hypersensitivity to anticholinergic drugs, lactose or any other components of the inhalation capsule delivery system.
Patients with known symptomatic prostatic hypertrophy or bladder neck obstruction.
Patients with known narrow-angle glaucoma.
Patients with a history of asthma, allergic rhinitis or atopy or who have a total blood eosinophil count ≥ 600/mm3. A repeat eosinophil count was not to be conducted in these patients.
Patients who were being treated with cromolyn sodium or nedocromil sodium had to stop these medications 1 month before Visit 1 (day -15).
Patients who were being treated with antihistamines (H1 receptor antagonists) or antileukotrienes had to stop these medications 1 month before Visit 1 (day -15).
Patients using oral corticosteroid medication at unstable doses (i.e., less than 6 weeks on a stable dose) or at a dose in excess of the equivalent of 10 mg of prednisone per day or 20 mg every other day.
Pregnant or nursing women or women of childbearing potential not using a medically approved means of contraception (i.e., oral contraceptives, intrauterine devices, diaphragm or Norplant®).
Patients with history or active alcohol or drug abuse.
Patients who had taken an investigational drug within 1 month or 10 half lives (whichever was greater) prior to Screening visit (Visit 1, day -15).
Limitation of exercise performance as a result of factors other than fatigue or exertional dyspnea such as arthritis in the leg, angina or claudication.
Patients who participated in any rehabilitation program for COPD within 6 weeks prior to Visit 1 (day -15).
12. IPD Sharing Statement
Links:
URL
http://trials.boehringer-ingelheim.com/content/dam/internet/opu/clinicaltrial/com_EN/results/205/205.131_U02-1202.pdf
Description
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Effect of Tiotropium on Exercise Tolerance in Patients With Chronic Obstructive Pulmonary Disease (COPD)
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