Chronic Obstructive Pulmonary Disease (COPD)
Conditions
Keywords
COPD, chronic obstructive pulmonary disease, indacaterol, long acting β2-agonist
Brief summary
This study was designed to provide pivotal confirmation of efficacy and safety data for 2 doses of indacaterol (150 and 300 µg once daily \[od\]) in patients with moderate to severe chronic obstructive pulmonary disease (COPD). Data from this study will be used for the registration of indacaterol in Japan.
Interventions
DRUGIndacaterol 150 μg capsules
Indacaterol was supplied in powder filled capsules with a single dose dry powder inhaler (SDDPI).
DRUGIndacaterol 300 μg capsules
Indacaterol was supplied in powder filled capsules with a single dose dry powder inhaler (SDDPI).
DRUGPlacebo capsules
Placebo was supplied in powder filled capsules with a single dose dry powder inhaler (SDDPI).
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
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
* Diagnosis of moderate-to-severe chronic obstructive pulmonary disease (COPD), as classified by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines and: 1. Smoking history of at least 20 pack-years. 2. Post-bronchodilator forced expiratory volume in 1 second (FEV1) \< 80% and ≥ 30% of the predicted normal value. 3. Post-bronchodilator FEV1/FVC (forced vital capacity) \< 70%.
Exclusion criteria
* Patients who have been hospitalized for a COPD exacerbation in the 6 weeks prior to screening or during the 14 day run-in period prior to randomization. * Patients requiring long-term oxygen therapy (\> 15 hours a day) for chronic hypoxemia. * Patients who have had a respiratory tract infection within 6 weeks prior to screening. * Patients with concomitant pulmonary disease. * Patients with a history 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 screening 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 or perform spirometry measurements. Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Trough Forced Expiratory Volume in 1 Second (FEV1) 24 Hours Post-dose at the End of Treatment (Week 12 + 1 Day, Day 85) | End of treatment (Week 12 + 1 day, Day 85) | FEV1 was measured with spirometry conducted according to internationally accepted standards. Trough FEV1 was defined as the average of measurements made 23 hours 10 minutes and 23 hours 45 minutes post-dose at the end of treatment. The analysis included baseline FEV1, FEV1 pre-dose and 30 minutes post-dose of salbutamol during screening, and FEV1 pre-dose and 60 minutes post-dose of ipratropium during screening as covariates. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Trough Forced Expiratory Volume in 1 Second (FEV1) at Week 2 | After Week 2 (Day 15) | FEV1 was measured with spirometry conducted according to internationally accepted standards. Trough FEV1 was defined as the average of measurements made 23 hours 10 minutes and 23 hours 45 minutes post-dose at Week 2. The analysis included baseline FEV1, FEV1 pre-dose and 30 minutes post-dose of salbutamol during screening, and FEV1 pre-dose and 60 minutes post-dose of ipratropium during screening as covariates. |
| Trough Forced Expiratory Volume in 1 Second (FEV1) at Week 4 | After Week 4 (Day 29) | FEV1 was measured with spirometry conducted according to internationally accepted standards. Trough FEV1 was defined as the average of measurements made 23 hours 10 minutes and 23 hours 45 minutes post-dose at Week 4. The analysis included baseline FEV1, FEV1 pre-dose and 30 minutes post-dose of salbutamol during screening, and FEV1 pre-dose and 60 minutes post-dose of ipratropium during screening as covariates. |
| Trough Forced Expiratory Volume in 1 Second (FEV1) at Week 8 | After Week 8 (Day 57) | FEV1 was measured with spirometry conducted according to internationally accepted standards. Trough FEV1 was defined as the average of measurements made 23 hours 10 minutes and 23 hours 45 minutes post-dose at Week 8. The analysis included baseline FEV1, FEV1 pre-dose and 30 minutes post-dose of salbutamol during screening, and FEV1 pre-dose and 60 minutes post-dose of ipratropium during screening as covariates. |
| Trough Forced Expiratory Volume in 1 Second (FEV1) at Week 12 (Day 84) | Prior to last dose at Week 12 (Day 84) | FEV1 was measured with spirometry conducted according to internationally accepted standards. Trough FEV1 was defined as the average of measurements made 50 and 15 minutes pre-dose at the end of treatment. The analysis included baseline FEV1, FEV1 pre-dose and 30 minutes post-dose of salbutamol during screening, and FEV1 pre-dose and 60 minutes post-dose of ipratropium during screening as covariates. |
Countries
Hong Kong, India, Japan, Singapore, South Korea, Taiwan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Indacaterol 150 μg Patients received indacaterol 150 μg delivered via a single dose dry powder inhaler (SDDPI) once daily (od) in the morning (between 8:00 and 11:00 AM). 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. | 114 |
| Indacaterol 300 μg Patients received indacaterol 300 μg delivered via a single dose dry powder inhaler (SDDPI) once daily (od) in the morning (between 8:00 and 11:00 AM). 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. | 116 |
| Placebo Patients received placebo delivered via a single dose dry powder inhaler (SDDPI) once daily (od) in the morning (between 8:00 and 11:00 AM). 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. | 117 |
| Total | 347 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Abnormal test procedure result(s) | 0 | 1 | 0 |
| Overall Study | Administrative problems | 1 | 7 | 4 |
| Overall Study | Adverse Event | 4 | 1 | 8 |
| Overall Study | Lost to Follow-up | 2 | 0 | 1 |
| Overall Study | Protocol deviation | 0 | 1 | 1 |
| Overall Study | Subject withdrew consent | 2 | 0 | 3 |
| Overall Study | Unsatisfactory therapeutic effect | 1 | 0 | 2 |
Baseline characteristics
| Characteristic | Indacaterol 150 μg | Indacaterol 300 μg | Placebo | Total |
|---|---|---|---|---|
| Age Continuous | 66.4 years STANDARD_DEVIATION 8.75 | 67.1 years STANDARD_DEVIATION 7.67 | 66.5 years STANDARD_DEVIATION 8.74 | 66.7 years STANDARD_DEVIATION 8.38 |
| Sex: Female, Male Female | 4 Participants | 3 Participants | 5 Participants | 12 Participants |
| Sex: Female, Male Male | 110 Participants | 113 Participants | 112 Participants | 335 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 24 / 114 | 26 / 116 | 26 / 117 |
| serious Total, serious adverse events | 4 / 114 | 2 / 116 | 6 / 117 |
Outcome results
Primary
Trough Forced Expiratory Volume in 1 Second (FEV1) 24 Hours Post-dose at the End of Treatment (Week 12 + 1 Day, Day 85)
FEV1 was measured with spirometry conducted according to internationally accepted standards. Trough FEV1 was defined as the average of measurements made 23 hours 10 minutes and 23 hours 45 minutes post-dose at the end of treatment. The analysis included baseline FEV1, FEV1 pre-dose and 30 minutes post-dose of salbutamol during screening, and FEV1 pre-dose and 60 minutes post-dose of ipratropium during screening as covariates.
Time frame: End of treatment (Week 12 + 1 day, Day 85)
Population: Intent-to-treat (ITT) population: All randomized patients who received at least 1 dose of study drug. The imputation technique used as last observation carried forward (LOCF).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Indacaterol 150 μg | Trough Forced Expiratory Volume in 1 Second (FEV1) 24 Hours Post-dose at the End of Treatment (Week 12 + 1 Day, Day 85) | 1.34 Liters | Standard Error 0.024 |
| Indacaterol 300 μg | Trough Forced Expiratory Volume in 1 Second (FEV1) 24 Hours Post-dose at the End of Treatment (Week 12 + 1 Day, Day 85) | 1.37 Liters | Standard Error 0.023 |
| Placebo | Trough Forced Expiratory Volume in 1 Second (FEV1) 24 Hours Post-dose at the End of Treatment (Week 12 + 1 Day, Day 85) | 1.17 Liters | Standard Error 0.025 |
Secondary
Trough Forced Expiratory Volume in 1 Second (FEV1) at Week 12 (Day 84)
FEV1 was measured with spirometry conducted according to internationally accepted standards. Trough FEV1 was defined as the average of measurements made 50 and 15 minutes pre-dose at the end of treatment. The analysis included baseline FEV1, FEV1 pre-dose and 30 minutes post-dose of salbutamol during screening, and FEV1 pre-dose and 60 minutes post-dose of ipratropium during screening as covariates.
Time frame: Prior to last dose at Week 12 (Day 84)
Population: Intent-to-treat (ITT) population: All randomized patients who received at least 1 dose of study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Indacaterol 150 μg | Trough Forced Expiratory Volume in 1 Second (FEV1) at Week 12 (Day 84) | 1.34 Liters | Standard Error 0.032 |
| Indacaterol 300 μg | Trough Forced Expiratory Volume in 1 Second (FEV1) at Week 12 (Day 84) | 1.34 Liters | Standard Error 0.03 |
| Placebo | Trough Forced Expiratory Volume in 1 Second (FEV1) at Week 12 (Day 84) | 1.13 Liters | Standard Error 0.031 |
Secondary
Trough Forced Expiratory Volume in 1 Second (FEV1) at Week 2
FEV1 was measured with spirometry conducted according to internationally accepted standards. Trough FEV1 was defined as the average of measurements made 23 hours 10 minutes and 23 hours 45 minutes post-dose at Week 2. The analysis included baseline FEV1, FEV1 pre-dose and 30 minutes post-dose of salbutamol during screening, and FEV1 pre-dose and 60 minutes post-dose of ipratropium during screening as covariates.
Time frame: After Week 2 (Day 15)
Population: Intent-to-treat (ITT) population: All randomized patients who received at least 1 dose of study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Indacaterol 150 μg | Trough Forced Expiratory Volume in 1 Second (FEV1) at Week 2 | 1.33 Liters | Standard Error 0.023 |
| Indacaterol 300 μg | Trough Forced Expiratory Volume in 1 Second (FEV1) at Week 2 | 1.34 Liters | Standard Error 0.023 |
| Placebo | Trough Forced Expiratory Volume in 1 Second (FEV1) at Week 2 | 1.17 Liters | Standard Error 0.024 |
Secondary
Trough Forced Expiratory Volume in 1 Second (FEV1) at Week 4
FEV1 was measured with spirometry conducted according to internationally accepted standards. Trough FEV1 was defined as the average of measurements made 23 hours 10 minutes and 23 hours 45 minutes post-dose at Week 4. The analysis included baseline FEV1, FEV1 pre-dose and 30 minutes post-dose of salbutamol during screening, and FEV1 pre-dose and 60 minutes post-dose of ipratropium during screening as covariates.
Time frame: After Week 4 (Day 29)
Population: Intent-to-treat (ITT) population: All randomized patients who received at least 1 dose of study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Indacaterol 150 μg | Trough Forced Expiratory Volume in 1 Second (FEV1) at Week 4 | 1.32 Liters | Standard Error 0.024 |
| Indacaterol 300 μg | Trough Forced Expiratory Volume in 1 Second (FEV1) at Week 4 | 1.33 Liters | Standard Error 0.022 |
| Placebo | Trough Forced Expiratory Volume in 1 Second (FEV1) at Week 4 | 1.18 Liters | Standard Error 0.024 |
Secondary
Trough Forced Expiratory Volume in 1 Second (FEV1) at Week 8
FEV1 was measured with spirometry conducted according to internationally accepted standards. Trough FEV1 was defined as the average of measurements made 23 hours 10 minutes and 23 hours 45 minutes post-dose at Week 8. The analysis included baseline FEV1, FEV1 pre-dose and 30 minutes post-dose of salbutamol during screening, and FEV1 pre-dose and 60 minutes post-dose of ipratropium during screening as covariates.
Time frame: After Week 8 (Day 57)
Population: Intent-to-treat (ITT) population: All randomized patients who received at least 1 dose of study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Indacaterol 150 μg | Trough Forced Expiratory Volume in 1 Second (FEV1) at Week 8 | 1.30 Liters | Standard Error 0.029 |
| Indacaterol 300 μg | Trough Forced Expiratory Volume in 1 Second (FEV1) at Week 8 | 1.32 Liters | Standard Error 0.027 |
| Placebo | Trough Forced Expiratory Volume in 1 Second (FEV1) at Week 8 | 1.14 Liters | Standard Error 0.03 |