Chronic Obstructive Pulmonary Disease
Conditions
Keywords
indacaterol, chronic obstructive pulmonary disease, exercise endurance, moderate to severe chronic obstructive pulmonary disease, COPD
Brief summary
This study compared the effect of indacaterol (300 μg once daily \[od\]) on exercise endurance with that of placebo in patients with moderate to severe chronic obstructive pulmonary disease.
Interventions
Indacaterol was supplied in powder filled capsules together with a single dose dry powder inhaler (SDDPI) device.
DRUGPlacebo
Placebo was supplied in powder filled capsules together with a single dose dry powder inhaler (SDDPI) device.
Sponsors
Novartis
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male and female adults aged ≥ 40 years, who have signed an informed consent form prior to initiation of any study-related procedure. * Co-operative outpatients with a diagnosis of moderate to severe chronic obstructive pulmonary disease (COPD), as classified by the GOLD Guidelines (2006), and: * Smoking history of at least 20 pack years. * Post-bronchodilator forced expiratory volume in 1 second (FEV1) \< 80% and ≥ 30% of the predicted normal value. * Post-bronchodilator FEV1/forced vital capacity (FVC) \< 70%.
Exclusion criteria
* Pregnant or nursing (lactating) women. * Women of child-bearing potential. * Patients who have been hospitalized for a COPD exacerbation in the 6 weeks prior to screening or during the run-in period. * Patients requiring oxygen therapy or who experience oxygen desaturation to \< 80% during cycle exercise on room air. * Patients with a Wmax value \< 20 W (as determined by the incremental cycle endurance test) at screening. * Patients who have had a respiratory tract infection within 6 weeks prior to screening. * Patients with contra-indications of cardiopulmonary exercise testing. * Patients with concomitant pulmonary disease. * Patients with a history (up to and including the screening visit) of asthma. * Patients with diabetes Type I or uncontrolled diabetes Type II. * Any patient with lung cancer or a history of lung cancer. * Any patient with active cancer or a history of cancer with less than 5 years disease free survival time. * Patients with a history of long QT syndrome or whose QTc interval (Bazett's) measured at the collection of informed consent visit (Visit 1) or randomization is prolonged. * Patients who have been vaccinated with live attenuated vaccines within 30 days prior to screening or during the run-in period. * Patients unable to successfully use a dry powder inhaler device, metered dose inhaler (MDI), or perform spirometry measurements. Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Exercise Duration Time Assessed by Constant-load Cycle Ergometry at the End of Each Treatment Period | End of each 3 week treatment period (last day of Weeks 3 and 9) | At the end of each 3 week treatment period, patients completed constant-load cycle ergometry testing at a work-rate of 75% of the Wmax determined at Screening. This work-rate was maintained until symptom limitation caused the patient to stop exercising. The time from the start of loaded pedaling until the patient stopped exercising was recorded. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Inspiratory Capacity (IC) Assessed at Rest With Spirometry at the End of Each Treatment Period 60 Minutes Pre-dose | End of each 3 week treatment period (last day of Weeks 3 and 9) | At the end of each 3 week treatment period 60 minutes before inhalation of study drug, IC was measured with spirometry conducted according to internationally accepted standards. The mean of 3 acceptable measurements was calculated and reported in liters. |
Countries
Belgium, Canada, Denmark, Italy, Spain, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Entire Study Population The entire study population includes the group of patients who received indacaterol 300 μg in the first treatment period followed by placebo in the second treatment period and the group of patients who received placebo in the first treatment period followed by indacaterol 300 μg in the second treatment period. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study. | 89 |
| Total | 89 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Treatment Period 1 | Adverse Event | 4 | 6 |
| Treatment Period 1 | Subject withdrew consent | 1 | 0 |
| Treatment Period 2 | Adverse Event | 2 | 2 |
Baseline characteristics
| Characteristic | Entire Study Population |
|---|---|
| Age Continuous | 62.8 years STANDARD_DEVIATION 8.2 |
| Sex: Female, Male Female | 27 Participants |
| Sex: Female, Male Male | 62 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 6 / 83 | 10 / 84 |
| serious Total, serious adverse events | 3 / 83 | 1 / 84 |
Outcome results
Primary
Exercise Duration Time Assessed by Constant-load Cycle Ergometry at the End of Each Treatment Period
At the end of each 3 week treatment period, patients completed constant-load cycle ergometry testing at a work-rate of 75% of the Wmax determined at Screening. This work-rate was maintained until symptom limitation caused the patient to stop exercising. The time from the start of loaded pedaling until the patient stopped exercising was recorded.
Time frame: End of each 3 week treatment period (last day of Weeks 3 and 9)
Population: Modified intent-to-treat (modified ITT) population: All randomized patients who received at least 1 dose of study drug. The number of patients analyzed for each treatment group was the number with non-missing values for the dependent and independent variables in the mixed model.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Indacaterol 300 μg | Exercise Duration Time Assessed by Constant-load Cycle Ergometry at the End of Each Treatment Period | 586 Seconds | Standard Error 30.3 |
| Placebo | Exercise Duration Time Assessed by Constant-load Cycle Ergometry at the End of Each Treatment Period | 475 Seconds | Standard Error 31.3 |
Secondary
Inspiratory Capacity (IC) Assessed at Rest With Spirometry at the End of Each Treatment Period 60 Minutes Pre-dose
At the end of each 3 week treatment period 60 minutes before inhalation of study drug, IC was measured with spirometry conducted according to internationally accepted standards. The mean of 3 acceptable measurements was calculated and reported in liters.
Time frame: End of each 3 week treatment period (last day of Weeks 3 and 9)
Population: Modified-intent-to-treat (modified ITT) population: All randomized patients who received at least 1 dose of study drug. The number of patients analyzed for each treatment group was the number with non-missing values for the dependent and independent variables in the mixed model.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Indacaterol 300 μg | Inspiratory Capacity (IC) Assessed at Rest With Spirometry at the End of Each Treatment Period 60 Minutes Pre-dose | 2.39 Liters | Standard Error 0.034 |
| Placebo | Inspiratory Capacity (IC) Assessed at Rest With Spirometry at the End of Each Treatment Period 60 Minutes Pre-dose | 2.25 Liters | Standard Error 0.034 |