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
Once daily via single-dose dry powder inhaler (SDDPI)
DRUGPlacebo to indacaterol
Once daily via SDDPI
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 COPD (moderate-to-severe as classified by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) Guidelines, 2008) and: 1. Smoking history of at least 10 pack-years 2. Post-bronchodilator FEV1 \<80% and ≥30% of the predicted normal value 3. 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 for 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 comorbid conditions Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Trough Forced Expiratory Volume in 1 Second (FEV1) After 12 Weeks of Treatment | after 12 weeks | Spirometry was conducted according to internationally accepted standards. Trough FEV1 was defined as the average of the 23 hour 10 minute and 23 hour 45 minute post-dose FEV1 readings. Mixed model used baseline FEV1, FEV1 prior to and 10-15 minutes post inhalation of albuterol, and FEV1 prior to and 50-70 minutes post inhalation of ipratropium as covariates. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Transition Dyspnoea Index (TDI) Focal Score After 12 Weeks of Treatment | after 12 weeks | TDI focal score is based on three domains: functional impairment, magnitude of task and magnitude of effort. Each domain is scored from -3 (major deterioration) to 3 (major improvement) to give an overall TDI focal score of -9 to 9 with a negative score indicating a deterioration from baseline. A 1 unit difference in the TDI focal score is clinically significant. Mixed model used baseline dyspnoea index, FEV1 prior to and 10-15 minutes post inhalation of albuterol, and FEV1 prior to and 50-70 minutes post inhalation of ipratropium as covariates. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Indacaterol 75 µg Indacaterol 75 µg inhaled once daily in the morning via Concept1, a single dose dry powder inhaler (SDDPI), for 12 weeks. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) albuterol was available for rescue use throughout the study. | 159 |
| Placebo Placebo to indacaterol inhaled once daily in the morning via Concept1, a SDDPI, for 12 weeks. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) albuterol was available for rescue use throughout the study. | 159 |
| Total | 318 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Abnormal laboratory value(s) | 1 | 0 |
| Overall Study | Administrative problems | 0 | 1 |
| Overall Study | Adverse Event | 3 | 3 |
| Overall Study | Lost to Follow-up | 1 | 2 |
| Overall Study | Protocol deviation | 1 | 1 |
| Overall Study | Unsatisfactory therapeutic effect | 0 | 4 |
| Overall Study | Withdrawal by Subject | 5 | 6 |
Baseline characteristics
| Characteristic | Indacaterol 75 µg | Placebo | Total |
|---|---|---|---|
| Age Continuous | 61.3 years STANDARD_DEVIATION 9.83 | 61.5 years STANDARD_DEVIATION 9.85 | 61.4 years STANDARD_DEVIATION 9.83 |
| Sex: Female, Male Female | 76 Participants | 70 Participants | 146 Participants |
| Sex: Female, Male Male | 83 Participants | 89 Participants | 172 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 58 / 159 | 46 / 159 |
| serious Total, serious adverse events | 4 / 159 | 4 / 159 |
Outcome results
Primary
Trough Forced Expiratory Volume in 1 Second (FEV1) After 12 Weeks of Treatment
Spirometry was conducted according to internationally accepted standards. Trough FEV1 was defined as the average of the 23 hour 10 minute and 23 hour 45 minute post-dose FEV1 readings. Mixed model used baseline FEV1, FEV1 prior to and 10-15 minutes post inhalation of albuterol, and FEV1 prior to and 50-70 minutes post inhalation of ipratropium as covariates.
Time frame: after 12 weeks
Population: Full Analysis Set included all randomized participants who received at least one dose of study drug. The endpoint was analyzed only for those participants who had data for this outcome measure. Missing data was imputed using last observation carried forward.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Indacaterol 75 µg | Trough Forced Expiratory Volume in 1 Second (FEV1) After 12 Weeks of Treatment | 1.49 Liters | Standard Error 0.016 |
| Placebo | Trough Forced Expiratory Volume in 1 Second (FEV1) After 12 Weeks of Treatment | 1.35 Liters | Standard Error 0.015 |
Secondary
Transition Dyspnoea Index (TDI) Focal Score After 12 Weeks of Treatment
TDI focal score is based on three domains: functional impairment, magnitude of task and magnitude of effort. Each domain is scored from -3 (major deterioration) to 3 (major improvement) to give an overall TDI focal score of -9 to 9 with a negative score indicating a deterioration from baseline. A 1 unit difference in the TDI focal score is clinically significant. Mixed model used baseline dyspnoea index, FEV1 prior to and 10-15 minutes post inhalation of albuterol, and FEV1 prior to and 50-70 minutes post inhalation of ipratropium as covariates.
Time frame: after 12 weeks
Population: Full Analysis Set included all randomized participants who received at least one dose of study medication. If data were missing or insufficient for any one of the domains a focal score was not calculated. Missing focal scores after week 4 were imputed using last observation carried forward.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Indacaterol 75 µg | Transition Dyspnoea Index (TDI) Focal Score After 12 Weeks of Treatment | 1.22 Score on a scale | Standard Error 0.234 |
| Placebo | Transition Dyspnoea Index (TDI) Focal Score After 12 Weeks of Treatment | 0.76 Score on a scale | Standard Error 0.235 |