Efficacy and Safety of Free Combination of Tiotropium + Formoterol Compared to Formoterol and Tiotropium in Patients With Chronic Obstructive Pulmonary Disease (COPD)
Primary Purpose
Pulmonary Disease, Chronic Obstructive
Status
Completed
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Tiotropium + formoterol combination
Tiotropium
Formoterol
Sponsored by
About this trial
This is an interventional treatment trial for Pulmonary Disease, Chronic Obstructive
Eligibility Criteria
Inclusion Criteria:
- All patients had to sign an informed consent consistent with International Conference on Harmonization Good Clinical Practice (ICH-GCP) guidelines prior to participation in the trial, which included medication washout and restrictions
All patients had to have a diagnosis of chronic obstructive pulmonary disease and had to meet the following spirometric criteria:
- Patients had to have relatively stable moderate to severe airway obstruction with an FEV1 ≤ 60% of predicted normal and FEV1 ≤ 70% of FVC (Visits 1 and 2)
- Male or female patients 40 years of age or older
- Patients had to be current or ex-smokers with a smoking history of more than 10 pack-years (Patients who had never smoked cigarettes had to be excluded)
- Patients had to be able to perform technically acceptable pulmonary function tests and had to be able to maintain records (Patient Daily Diary Record) during the study period as required in the protocol
- Patients had to be able to inhale medication in a competent manner from the HandiHaler® device, the Blue Inhaler device and from a metered dose inhaler (MDI)
Exclusion Criteria:
- Patients with significant diseases other than COPD had to be excluded. A significant disease was defined as a disease which in the opinion of the investigator may either put the patient at risk because of participation in the study or a disease which may influence the results of the study or the patient's ability to participate in the study
- Patients with clinically relevant abnormal baseline haematology, blood chemistry, or urinalysis if the abnormality defined a disease listed as an exclusion criterion
- All patients with an serum glutamate oxaloacetate transaminase (SGOT) > 80 IU/L, serum glutamate pyruvate transaminase (SGPT) > 80 IU/L, bilirubin > 17 μmol/L or creatinine > 110 μmol/L (males) / 95 μmol/L (females) had to be excluded regardless of clinical condition
- Patients with a recent history (i.e., six months or less) of myocardial infarction
- Patients with any cardiac arrhythmia requiring drug therapy or who had been hospitalised for heart failure within the past three years
- Patients with a history of cancer within the last five years. Patients with treated basal cell carcinoma were allowed
Patients with known symptomatic prostatic hypertrophy or bladder neck obstruction.
Patients with prostatic hypertrophy controlled by medication were allowed
- Patients with known narrow-angle glaucoma
- Patients with a history of asthma, allergic rhinitis or who had a total blood eosinophil count ≥600 mm3
- Patients with a history of life-threatening pulmonary obstruction, or a history of cystic fibrosis or clinically evident bronchiectasis
- Patients with known active tuberculosis
- Patients with a history of and/or active significant alcohol or drug abuse. See exclusion criterion No. 1.
- Patients who had undergone thoracotomy with pulmonary resection. Patients with a history of thoracotomy for other reasons had to be evaluated as per exclusion criterion No. 1
- Patients who completed a pulmonary rehabilitation program in the six weeks prior to the Screening Visit (Visit 1)
- Patients who regularly used daytime oxygen therapy
- Patients who had taken an investigational drug within one month or six half lives (whichever is greater) prior to Screening Visit (Visit 1)
- Patients who were treated with beta-blocker medications. Note: cardioselective beta blocker eye medications (e.g. Betoptic®) for treatment of non-narrow angle glaucoma were allowed
- Patients who were treated with oral beta-adrenergics
- Patients who were treated with cromolyn sodium or nedocromil sodium
- Patients who were treated with antihistamines (H1 receptor antagonists), antileukotrienes or leukotriene receptor antagonists for asthma or excluded allergic conditions. See exclusion criterion No. 9
- Patients using 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 prednisone per day or 20 mg every other day
- Patients with known hypersensitivity to anticholinergic drugs, beta-adrenergics, lactose or any other components of the inhalation capsule delivery systems
- Pregnant or nursing women or women of childbearing potential not using a medically approved means of contraception for the previous 3 months (i.e. oral contraceptives, intrauterine devices, diaphragm or subdermal implants e.g., Norplant®)
- Patients with previous participation (receipt of randomised treatment) in this study
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Active Comparator
Active Comparator
Arm Label
tiotropium + formoterol
tiotropium
formoterol
Arm Description
Outcomes
Primary Outcome Measures
Change in area under the curve from pre-dose to 12 hours of the forced expiratory volume in one second (FEV1 AUC0-12h)
Change in FEV1 AUC0-24h
Secondary Outcome Measures
Change in FEV1 AUC12-24h
Change in AUC of the forced vital capacity (FVC AUC0-12h)
Change in FVC AUC0-24h
Change in FVC AUC12-24h
Change in peak FEV1 response
Change in trough FEV1 response
Change in peak FVC response
Change in trough FVC response
Individual FEV1measurements at each time point
Individual FVCmeasurements at each time point
Peak expiratory flow rate (PEFR)
measured twice daily
Number of inhalations of rescue salbutamol therapy used per day
Assessment of daytime COPD symptom score rated on a 6-point rating scale
Assessment of nighttime COPD symptom score rated on a 5-point rating scale
Number of patients with adverse events
Full Information
NCT ID
NCT02238119
First Posted
September 11, 2014
Last Updated
September 11, 2014
Sponsor
Boehringer Ingelheim
1. Study Identification
Unique Protocol Identification Number
NCT02238119
Brief Title
Efficacy and Safety of Free Combination of Tiotropium + Formoterol Compared to Formoterol and Tiotropium in Patients With Chronic Obstructive Pulmonary Disease (COPD)
Official Title
A Randomised, Double-blind, Double-dummy, Crossover Efficacy and Safety Comparison of 6-week Treatment Periods of the Free Combination of Tiotropium Inhalation Powder Capsule (18 μg) + Formoterol Inhalation Powder Capsule (12 μg) QD, Tiotropium Inhalation Powder Capsule (18 μg) QD and Formoterol Inhalation Powder Capsule (12 μg) BID in Patients With COPD
Study Type
Interventional
2. Study Status
Record Verification Date
September 2014
Overall Recruitment Status
Completed
Study Start Date
February 2002 (undefined)
Primary Completion Date
August 2002 (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 evaluate the lung function response to the free once-daily combination of tiotropium + formoterol compared to formoterol BID and tiotropium QD
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 2
Interventional Study Model
Crossover Assignment
Masking
Double
Allocation
Randomized
Enrollment
74 (Actual)
8. Arms, Groups, and Interventions
Arm Title
tiotropium + formoterol
Arm Type
Experimental
Arm Title
tiotropium
Arm Type
Active Comparator
Arm Title
formoterol
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
Tiotropium + formoterol combination
Intervention Type
Drug
Intervention Name(s)
Tiotropium
Intervention Type
Drug
Intervention Name(s)
Formoterol
Primary Outcome Measure Information:
Title
Change in area under the curve from pre-dose to 12 hours of the forced expiratory volume in one second (FEV1 AUC0-12h)
Time Frame
after 6 weeks of each treatment
Title
Change in FEV1 AUC0-24h
Time Frame
after 6 weeks of each treatment
Secondary Outcome Measure Information:
Title
Change in FEV1 AUC12-24h
Time Frame
after 6 weeks of each treatment
Title
Change in AUC of the forced vital capacity (FVC AUC0-12h)
Time Frame
after 6 weeks of each treatment
Title
Change in FVC AUC0-24h
Time Frame
after 6 weeks of each treatment
Title
Change in FVC AUC12-24h
Time Frame
after 6 weeks of each treatment
Title
Change in peak FEV1 response
Time Frame
after 6 weeks of each treatment
Title
Change in trough FEV1 response
Time Frame
after 6 weeks of each treatment
Title
Change in peak FVC response
Time Frame
after 6 weeks of each treatment
Title
Change in trough FVC response
Time Frame
after 6 weeks of each treatment
Title
Individual FEV1measurements at each time point
Time Frame
up to 6 weeks
Title
Individual FVCmeasurements at each time point
Time Frame
up to 6 weeks
Title
Peak expiratory flow rate (PEFR)
Description
measured twice daily
Time Frame
weeks 4 to 6 of each treatment period
Title
Number of inhalations of rescue salbutamol therapy used per day
Time Frame
weeks 4 to 6 of each treatment period
Title
Assessment of daytime COPD symptom score rated on a 6-point rating scale
Time Frame
weeks 4 to 6 of each treatment period
Title
Assessment of nighttime COPD symptom score rated on a 5-point rating scale
Time Frame
weeks 4 to 6 of each treatment period
Title
Number of patients with adverse events
Time Frame
up to 23 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
All patients had to sign an informed consent consistent with International Conference on Harmonization Good Clinical Practice (ICH-GCP) guidelines prior to participation in the trial, which included medication washout and restrictions
All patients had to have a diagnosis of chronic obstructive pulmonary disease and had to meet the following spirometric criteria:
Patients had to have relatively stable moderate to severe airway obstruction with an FEV1 ≤ 60% of predicted normal and FEV1 ≤ 70% of FVC (Visits 1 and 2)
Male or female patients 40 years of age or older
Patients had to be current or ex-smokers with a smoking history of more than 10 pack-years (Patients who had never smoked cigarettes had to be excluded)
Patients had to be able to perform technically acceptable pulmonary function tests and had to be able to maintain records (Patient Daily Diary Record) during the study period as required in the protocol
Patients had to be able to inhale medication in a competent manner from the HandiHaler® device, the Blue Inhaler device and from a metered dose inhaler (MDI)
Exclusion Criteria:
Patients with significant diseases other than COPD had to be excluded. A significant disease was defined as a disease which in the opinion of the investigator may either put the patient at risk because of participation in the study or a disease which may influence the results of the study or the patient's ability to participate in the study
Patients with clinically relevant abnormal baseline haematology, blood chemistry, or urinalysis if the abnormality defined a disease listed as an exclusion criterion
All patients with an serum glutamate oxaloacetate transaminase (SGOT) > 80 IU/L, serum glutamate pyruvate transaminase (SGPT) > 80 IU/L, bilirubin > 17 μmol/L or creatinine > 110 μmol/L (males) / 95 μmol/L (females) had to be excluded regardless of clinical condition
Patients with a recent history (i.e., six months or less) of myocardial infarction
Patients with any cardiac arrhythmia requiring drug therapy or who had been hospitalised for heart failure within the past three years
Patients with a history of cancer within the last five years. Patients with treated basal cell carcinoma were allowed
Patients with known symptomatic prostatic hypertrophy or bladder neck obstruction.
Patients with prostatic hypertrophy controlled by medication were allowed
Patients with known narrow-angle glaucoma
Patients with a history of asthma, allergic rhinitis or who had a total blood eosinophil count ≥600 mm3
Patients with a history of life-threatening pulmonary obstruction, or a history of cystic fibrosis or clinically evident bronchiectasis
Patients with known active tuberculosis
Patients with a history of and/or active significant alcohol or drug abuse. See exclusion criterion No. 1.
Patients who had undergone thoracotomy with pulmonary resection. Patients with a history of thoracotomy for other reasons had to be evaluated as per exclusion criterion No. 1
Patients who completed a pulmonary rehabilitation program in the six weeks prior to the Screening Visit (Visit 1)
Patients who regularly used daytime oxygen therapy
Patients who had taken an investigational drug within one month or six half lives (whichever is greater) prior to Screening Visit (Visit 1)
Patients who were treated with beta-blocker medications. Note: cardioselective beta blocker eye medications (e.g. Betoptic®) for treatment of non-narrow angle glaucoma were allowed
Patients who were treated with oral beta-adrenergics
Patients who were treated with cromolyn sodium or nedocromil sodium
Patients who were treated with antihistamines (H1 receptor antagonists), antileukotrienes or leukotriene receptor antagonists for asthma or excluded allergic conditions. See exclusion criterion No. 9
Patients using 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 prednisone per day or 20 mg every other day
Patients with known hypersensitivity to anticholinergic drugs, beta-adrenergics, lactose or any other components of the inhalation capsule delivery systems
Pregnant or nursing women or women of childbearing potential not using a medically approved means of contraception for the previous 3 months (i.e. oral contraceptives, intrauterine devices, diaphragm or subdermal implants e.g., Norplant®)
Patients with previous participation (receipt of randomised treatment) in this study
12. IPD Sharing Statement
Links:
URL
http://trials.boehringer-ingelheim.com
Description
Related Info
Learn more about this trial
Efficacy and Safety of Free Combination of Tiotropium + Formoterol Compared to Formoterol and Tiotropium in Patients With Chronic Obstructive Pulmonary Disease (COPD)
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