Chronic Obstructive Pulmonary Disease
Conditions
Keywords
COPD, indacaterol
Brief summary
This 12-week study evaluated the efficacy and safety of indacaterol versus placebo.
Interventions
DRUGIndacaterol 75 μg
Indacaterol was supplied in powder filled capsules together with a single-dose dry-powder inhaler (SDDPI) device.
DRUGPlacebo to indacaterol
Placebo to indacaterol was supplied in powder filled capsules together with a single-dose dry-powder inhaler (SDDPI) device.
Sponsors
Novartis
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 chronic obstructive pulmonary disease (COPD) (moderate-to-severe as classified by the Global Initiative for Chronic Obstructive Lung Disease \[GOLD\] Guidelines, 2008) and: * Smoking history of at least 10 pack-years * Post-bronchodilator forced expiratory volume in 1 second (FEV1) \< 80% and ≥ 30% of the predicted normal value * Post-bronchodilator FEV1/FVC (forced vital capacity) \< 70%
Exclusion criteria
* Patients who have had a COPD exacerbation requiring systemic corticosteroids and/or antibiotics and/or hospitalization in the 6 weeks prior to screening * 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 * Patients with a history of certain cardiovascular co-morbid conditions 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 the Study (Week 12 + 1 Day, Day 85) | 24 hours post-dose at the end of the study (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 10-15 minutes post-dose of albuterol during screening, and FEV1 pre-dose and 50-70 minutes post-dose of ipratropium during screening as covariates. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Transition Dyspnea Index (TDI) Total Score at the End of the Study (Week 12, Day 84) | End of the study (Week 12, Day 84) | An independent (where feasible), trained assessor interviewed the patient and rated the degree of impairment due to dyspnea on a scale from -3 (major deterioration) to 3 (major improvement) on 3 domains (functional impairment, magnitude of task, and magnitude of effort) in comparison with baseline. A total score of the 3 domains ranged from -9 to 9; minus scores indicate deterioration. The analysis included baseline dyspnea index, FEV1 pre-dose and 10-15 minutes post-dose of albuterol during screening, and FEV1 pre-dose and 50-70 minutes post-dose of ipratropium during screening as covariates. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Indacaterol 75 μg Patients inhaled indacaterol 75 μg once daily in the morning between 8:00 AM and 11:00 AM via a single-dose dry-powder inhaler (SDDPI) for 12 weeks. 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. | 163 |
| Placebo to Indacaterol Patients inhaled placebo to indacaterol once daily in the morning between 8:00 AM and 11:00 AM via a single-dose dry-powder inhaler (SDDPI) for 12 weeks. 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. | 160 |
| Total | 323 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Abnormal laboratory value(s) | 0 | 1 |
| Overall Study | Abnormal test procedure result(s) | 1 | 0 |
| Overall Study | Adverse Event | 9 | 10 |
| Overall Study | Death | 0 | 2 |
| Overall Study | Lost to Follow-up | 1 | 1 |
| Overall Study | Protocol deviation | 3 | 4 |
| Overall Study | Subject withdrew consent | 4 | 9 |
| Overall Study | Unsatisfactory therapeutic effect | 1 | 3 |
Baseline characteristics
| Characteristic | Indacaterol 75 μg | Placebo to Indacaterol | Total |
|---|---|---|---|
| Age Continuous | 64.0 years STANDARD_DEVIATION 8.29 | 64.1 years STANDARD_DEVIATION 9.43 | 64.0 years STANDARD_DEVIATION 8.86 |
| Sex: Female, Male Female | 74 Participants | 73 Participants | 147 Participants |
| Sex: Female, Male Male | 89 Participants | 87 Participants | 176 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 29 / 163 | 23 / 160 |
| serious Total, serious adverse events | 4 / 163 | 9 / 160 |
Outcome results
Primary
Trough Forced Expiratory Volume in 1 Second (FEV1) 24 Hours Post-dose at the End of the Study (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 10-15 minutes post-dose of albuterol during screening, and FEV1 pre-dose and 50-70 minutes post-dose of ipratropium during screening as covariates.
Time frame: 24 hours post-dose at the end of the study (Week 12 + 1 day, Day 85)
Population: Full analysis set: All randomized patients who received at least 1 dose of study drug, last observation carried forward (LOCF).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Indacaterol 75 μg | Trough Forced Expiratory Volume in 1 Second (FEV1) 24 Hours Post-dose at the End of the Study (Week 12 + 1 Day, Day 85) | 1.38 Liters | Standard Error 0.013 |
| Placebo to Indacaterol | Trough Forced Expiratory Volume in 1 Second (FEV1) 24 Hours Post-dose at the End of the Study (Week 12 + 1 Day, Day 85) | 1.26 Liters | Standard Error 0.013 |
Secondary
Transition Dyspnea Index (TDI) Total Score at the End of the Study (Week 12, Day 84)
An independent (where feasible), trained assessor interviewed the patient and rated the degree of impairment due to dyspnea on a scale from -3 (major deterioration) to 3 (major improvement) on 3 domains (functional impairment, magnitude of task, and magnitude of effort) in comparison with baseline. A total score of the 3 domains ranged from -9 to 9; minus scores indicate deterioration. The analysis included baseline dyspnea index, FEV1 pre-dose and 10-15 minutes post-dose of albuterol during screening, and FEV1 pre-dose and 50-70 minutes post-dose of ipratropium during screening as covariates.
Time frame: End of the study (Week 12, Day 84)
Population: Full analysis set: All randomized patients who received at least 1 dose of study drug, last observation carried forward (LOCF).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Indacaterol 75 μg | Transition Dyspnea Index (TDI) Total Score at the End of the Study (Week 12, Day 84) | 1.34 Units on a scale | Standard Error 0.284 |
| Placebo to Indacaterol | Transition Dyspnea Index (TDI) Total Score at the End of the Study (Week 12, Day 84) | 0.11 Units on a scale | Standard Error 0.287 |