Efficacy and Safety of Tiotropium Compared to Salmeterol and Placebo in Patients With Chronic Obstructive Bronchitis (COPD)
Primary Purpose
Pulmonary Disease, Chronic Obstructive
Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Tiotropium inhalation powder capsules
Salmeterol inhalation aerosol
Placebo inhalation aerosol
Placebo inhalation powder capsules
Sponsored by
About this trial
This is an interventional treatment trial for Pulmonary Disease, Chronic Obstructive
Eligibility Criteria
Inclusion Criteria:
- Age ≥ 40 years.
A diagnosis of relatively stable, moderate to severe COPD with:
- Screening FEV1 ≤ 60% of predicted normal value (calculated according to European Community for Coal and Steel (ECCS) criteria and screening FEV1/FVC ≤ 70%
- Smoking history ≥ 10 pack-years (a pack-year is 20 cigarettes per day for one year or equivalent)
- Ability to be trained in the proper use of the HandiHaler® device and Metered Dose Inhaler (MDI).
- Ability to perform all study related tests including the Shuttle Walking Test, acceptable pulmonary function tests, including Peak expiratory flow rate (PEFR) measurements, and maintenance of diary card records.
- Ability to give written informed consent in accordance with Good Clinical Practice and local regulations.
Exclusion Criteria:
- Clinically significant diseases other than COPD.
- Patients with clinically relevant abnormal baseline haematology, blood chemistry or urinalysis, if the abnormality defines a disease listed as an exclusion criterion, will be excluded.
- All patients with a serum glutamic oxaloacetic transaminase (SGOT) > 80 IU/L, serum glutamic pyruvic transaminase (SGPT) > 80 IU/L, bilirubin >2.0 mg/dL or creatinine > 2.0 mg/dL will be excluded regardless of clinical condition.
- A recent history (i.e., one year or less) of myocardial infarction.
- Any cardiac arrhythmia requiring drug therapy or hospitalisation for heart failure within the past three years.
- Inability to abstain from regular daytime use of oxygen therapy for more than 1 hour per day.
- Known active tuberculosis.
- History of cancer within the last five years (excluding basal cell carcinoma)
- History of life-threatening pulmonary obstruction, or a history of cystic fibrosis or bronchiectasis.
- Patients who have undergone thoracotomy with pulmonary resection.
- Any upper respiratory infection in the past six weeks prior to the screening visit or during the run-in period.
- Current participation in a pulmonary rehabilitation programme or completion of a pulmonary rehabilitation programme in the six week prior to the screening visit.
- Known hypersensitivity to anticholinergic drugs, salmeterol, or any of the components of the lactose powder capsule or MDI delivery systems.
- Known symptomatic prostatic hypertrophy or bladder neck obstruction.
- Patients with known narrow-angle glaucoma.
- Current treatment with cromolyn sodium or nedocromil sodium.
- Current treatment with antihistamines (H1 receptor antagonists).
- Oral corticosteroid medication at unstable doses (i.e., less than six weeks on a stable dose) or at doses in excess of the equivalent of 10 mg of prednisolone per day or 20 mg every other day.
- Current use of β-blocker medication.
- Current treatment with monoamine oxidase inhibitors or tricyclic antidepressants.
- Pregnant or nursing women or women of childbearing potential not using a medically approved means of contraception.
- Patients with a history of asthma, allergic rhinitis or atopy or who have a total blood eosinophil count > 600mm3.
- History of and/or active significant alcohol or drug abuse.
- Concomitant or recent use of an investigational drug within one month or six half lives (whichever is greater) prior to the screening visit.
- Changes in the pulmonary therapeutic plan within the six weeks prior to the screening visit.
- Inability to comply with the medication restrictions specified in Section 4.2 of the trial protocol
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Active Comparator
Placebo Comparator
Arm Label
Tiotropium
Salmeterol
Placebo
Arm Description
Outcomes
Primary Outcome Measures
Trough forced expiratory volume in one second (FEV1) response
Transition Dyspnoea Index (TDI) focal score
Secondary Outcome Measures
Average FEV1 response
Peak FEV1 response
Trough FVC (forced vital capacity) response
Average FVC (forced vital capacity) response
Peak FVC (forced vital capacity) response
Individual FEV1 measurement
Individual FVC measurement
Patient peak expiratory flow rates (PEFR) twice daily
Physician's global evaluation on an 8-point-scale
COPD symptom scores (wheezing, shortness of breath, coughing and tightness of chest)
Amount of salbutamol therapy used during the treatment period
Number and length of exacerbations of COPD
Number and length of hospitalizations for respiratory disease
Changes from baseline in St. George's Hospital Respiratory Questionnaire (SGRQ)
Changes from baseline in Mahler Dyspnoea Index (Baseline Dyspnoea Index /Transitional Dyspnoea Index (BDI/TDI))
Health resource utilisation
Patient preference measures
patient satisfaction questionnaire score
Changes from baseline in Shuttle walking tests (SWT) and Borg dyspnea score
Occurrence of Adverse Events
Changes from baseline in pulse rate and blood pressure in conjunction with spirometry
Changes from baseline in physical examination and ECG
Changes from baseline in laboratory tests
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02173691
Brief Title
Efficacy and Safety of Tiotropium Compared to Salmeterol and Placebo in Patients With Chronic Obstructive Bronchitis (COPD)
Official Title
A Multiple Dose Comparison of Tiotropium Inhalation Capsules, Salmeterol Inhalation Aerosol and Placebo in a Six-Month, Double-Blind, Double-Dummy, Safety and Efficacy Study in Patients With Chronic Obstructive Pulmonary Disease (COPD)
Study Type
Interventional
2. Study Status
Record Verification Date
June 2014
Overall Recruitment Status
Completed
Study Start Date
February 1999 (undefined)
Primary Completion Date
May 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
The objective of this study is to compare the long-term (six month) bronchodilator efficacy and safety of tiotropium inhalation capsules, salmeterol inhalation aerosol and placebo inpatients with COPD.
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
584 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Tiotropium
Arm Type
Experimental
Arm Title
Salmeterol
Arm Type
Active Comparator
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Tiotropium inhalation powder capsules
Intervention Type
Drug
Intervention Name(s)
Salmeterol inhalation aerosol
Intervention Type
Drug
Intervention Name(s)
Placebo inhalation aerosol
Intervention Type
Drug
Intervention Name(s)
Placebo inhalation powder capsules
Primary Outcome Measure Information:
Title
Trough forced expiratory volume in one second (FEV1) response
Time Frame
6 months
Title
Transition Dyspnoea Index (TDI) focal score
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Average FEV1 response
Time Frame
30 and 60 min prior to and 30 and 60 min, 2 and 3 h post treatment on day 1, week 2, 8, 16, 24
Title
Peak FEV1 response
Time Frame
30 and 60 min prior to and 30 and 60 min, 2 and 3 h post treatment on day 1, week 2, 8, 16, 24
Title
Trough FVC (forced vital capacity) response
Time Frame
30 and 60 min prior to and 30 and 60 min, 2 and 3 h post treatment on day 1, week 2, 8, 16, 24
Title
Average FVC (forced vital capacity) response
Time Frame
30 and 60 min prior to and 30 and 60 min, 2 and 3 h post treatment on day 1, week 2, 8, 16, 24
Title
Peak FVC (forced vital capacity) response
Time Frame
30 and 60 min prior to and 30 and 60 min, 2 and 3 h post treatment on day 1, week 2, 8, 16, 24
Title
Individual FEV1 measurement
Time Frame
Day 1, weeks 2, 8, 16, 24
Title
Individual FVC measurement
Time Frame
Day 1, weeks 2, 8, 16, 24
Title
Patient peak expiratory flow rates (PEFR) twice daily
Time Frame
27 weeks
Title
Physician's global evaluation on an 8-point-scale
Time Frame
27 weeks
Title
COPD symptom scores (wheezing, shortness of breath, coughing and tightness of chest)
Time Frame
27 weeks
Title
Amount of salbutamol therapy used during the treatment period
Time Frame
27 weeks
Title
Number and length of exacerbations of COPD
Time Frame
27 weeks
Title
Number and length of hospitalizations for respiratory disease
Time Frame
27 weeks
Title
Changes from baseline in St. George's Hospital Respiratory Questionnaire (SGRQ)
Time Frame
Day 1, week 8, 16, 24 and 27
Title
Changes from baseline in Mahler Dyspnoea Index (Baseline Dyspnoea Index /Transitional Dyspnoea Index (BDI/TDI))
Time Frame
Baseline, week 8, 16, 24, 27
Title
Health resource utilisation
Time Frame
27 weeks
Title
Patient preference measures
Description
patient satisfaction questionnaire score
Time Frame
Day 1 and week 24
Title
Changes from baseline in Shuttle walking tests (SWT) and Borg dyspnea score
Time Frame
Day 1, week 8, 16, 24, 27
Title
Occurrence of Adverse Events
Time Frame
27 weeks
Title
Changes from baseline in pulse rate and blood pressure in conjunction with spirometry
Time Frame
baseline, Day 1, week 2, 8, 16 and 24
Title
Changes from baseline in physical examination and ECG
Time Frame
baseline and week 24
Title
Changes from baseline in laboratory tests
Time Frame
baseline and week 24
10. Eligibility
Sex
All
Minimum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age ≥ 40 years.
A diagnosis of relatively stable, moderate to severe COPD with:
Screening FEV1 ≤ 60% of predicted normal value (calculated according to European Community for Coal and Steel (ECCS) criteria and screening FEV1/FVC ≤ 70%
Smoking history ≥ 10 pack-years (a pack-year is 20 cigarettes per day for one year or equivalent)
Ability to be trained in the proper use of the HandiHaler® device and Metered Dose Inhaler (MDI).
Ability to perform all study related tests including the Shuttle Walking Test, acceptable pulmonary function tests, including Peak expiratory flow rate (PEFR) measurements, and maintenance of diary card records.
Ability to give written informed consent in accordance with Good Clinical Practice and local regulations.
Exclusion Criteria:
Clinically significant diseases other than COPD.
Patients with clinically relevant abnormal baseline haematology, blood chemistry or urinalysis, if the abnormality defines a disease listed as an exclusion criterion, will be excluded.
All patients with a serum glutamic oxaloacetic transaminase (SGOT) > 80 IU/L, serum glutamic pyruvic transaminase (SGPT) > 80 IU/L, bilirubin >2.0 mg/dL or creatinine > 2.0 mg/dL will be excluded regardless of clinical condition.
A recent history (i.e., one year or less) of myocardial infarction.
Any cardiac arrhythmia requiring drug therapy or hospitalisation for heart failure within the past three years.
Inability to abstain from regular daytime use of oxygen therapy for more than 1 hour per day.
Known active tuberculosis.
History of cancer within the last five years (excluding basal cell carcinoma)
History of life-threatening pulmonary obstruction, or a history of cystic fibrosis or bronchiectasis.
Patients who have undergone thoracotomy with pulmonary resection.
Any upper respiratory infection in the past six weeks prior to the screening visit or during the run-in period.
Current participation in a pulmonary rehabilitation programme or completion of a pulmonary rehabilitation programme in the six week prior to the screening visit.
Known hypersensitivity to anticholinergic drugs, salmeterol, or any of the components of the lactose powder capsule or MDI delivery systems.
Known symptomatic prostatic hypertrophy or bladder neck obstruction.
Patients with known narrow-angle glaucoma.
Current treatment with cromolyn sodium or nedocromil sodium.
Current treatment with antihistamines (H1 receptor antagonists).
Oral corticosteroid medication at unstable doses (i.e., less than six weeks on a stable dose) or at doses in excess of the equivalent of 10 mg of prednisolone per day or 20 mg every other day.
Current use of β-blocker medication.
Current treatment with monoamine oxidase inhibitors or tricyclic antidepressants.
Pregnant or nursing women or women of childbearing potential not using a medically approved means of contraception.
Patients with a history of asthma, allergic rhinitis or atopy or who have a total blood eosinophil count > 600mm3.
History of and/or active significant alcohol or drug abuse.
Concomitant or recent use of an investigational drug within one month or six half lives (whichever is greater) prior to the screening visit.
Changes in the pulmonary therapeutic plan within the six weeks prior to the screening visit.
Inability to comply with the medication restrictions specified in Section 4.2 of the trial protocol
12. IPD Sharing Statement
Links:
URL
http://trials.boehringer-ingelheim.com/content/dam/internet/opu/clinicaltrial/com_EN/results/205/205.137_U01-1231-02.pdf
Description
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Efficacy and Safety of Tiotropium Compared to Salmeterol and Placebo in Patients With Chronic Obstructive Bronchitis (COPD)
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