Chronic Obstructive Pulmonary Disease (COPD)
Conditions
Keywords
COPD, indacaterol, long-acting β2-agonist, adults
Brief summary
This study evaluated the efficacy and safety of two doses of indacaterol in adults aged 40 or over with chronic obstructive pulmonary disease (COPD) in China and in two other countries.
Interventions
Indacaterol was supplied in powder-filled capsules with a single-dose dry-powder inhaler (SDDPI).
Indacaterol was supplied in powder-filled capsules with a single-dose dry-powder inhaler (SDDPI).
DRUGPlacebo to indacaterol
Placebo to indacaterol 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
* Adults aged ≥ 40 years * Diagnosis of chronic obstructive pulmonary disease (COPD) (moderate to severe as classified by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) Guidelines, 2007) and: 1. Smoking history of at least 10 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 received systemic corticosteroids for a COPD exacerbation in the 6 weeks prior to screening or during the run-in period * 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 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) at Week 12 + 1 Day, Day 85 | 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 and FEV1 pre-dose and 10-15 minutes post-dose of salbutamol/albuterol during screening as covariates. |
Countries
Australia, China, India
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Indacaterol 150 μg Patients inhaled indacaterol 150 μg via a single-dose dry-powder inhaler (SDDPI) once daily (od) in the morning (between 8:00 and 11:00 AM) for 26 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. | 187 |
| Indacaterol 300 μg Patients inhaled indacaterol 300 μg via a single-dose dry-powder inhaler (SDDPI) once daily (od) in the morning (between 8:00 and 11:00 AM) for 26 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. | 188 |
| Placebo to Indacaterol Patients inhaled placebo to indacaterol via a single-dose dry-powder inhaler (SDDPI) once daily (od) in the morning (between 8:00 and 11:00 AM) for 26 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. | 186 |
| Total | 561 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Abnormal laboratory value(s) | 0 | 0 | 1 |
| Overall Study | Abnormal test procedure result(s) | 1 | 2 | 0 |
| Overall Study | Administrative problems | 2 | 0 | 4 |
| Overall Study | Adverse Event | 12 | 10 | 10 |
| Overall Study | Lost to Follow-up | 1 | 1 | 6 |
| Overall Study | Protocol deviation | 0 | 1 | 1 |
| Overall Study | Subject withdrew consent | 5 | 6 | 5 |
| Overall Study | Unsatisfactory therapeutic effect | 1 | 6 | 6 |
Baseline characteristics
| Characteristic | Indacaterol 150 μg | Indacaterol 300 μg | Placebo to Indacaterol | Total |
|---|---|---|---|---|
| Age Continuous | 66.2 years STANDARD_DEVIATION 8.01 | 65.5 years STANDARD_DEVIATION 8.86 | 64.6 years STANDARD_DEVIATION 9.3 | 65.4 years STANDARD_DEVIATION 8.75 |
| Sex: Female, Male Female | 12 Participants | 7 Participants | 13 Participants | 32 Participants |
| Sex: Female, Male Male | 175 Participants | 181 Participants | 173 Participants | 529 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 | 38 / 187 | 50 / 188 | 47 / 186 |
| serious Total, serious adverse events | 12 / 187 | 12 / 188 | 15 / 186 |
Outcome results
Primary
Trough Forced Expiratory Volume in 1 Second (FEV1) at 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 and FEV1 pre-dose and 10-15 minutes post-dose of salbutamol/albuterol during screening as covariates.
Time frame: Week 12 + 1 day, Day 85
Population: Intent-to-treat (ITT) population: All randomized patients who received at least 1 dose of study drug. Last observation carried forward (LOCF) was utilized to impute missing data.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Indacaterol 150 μg | Trough Forced Expiratory Volume in 1 Second (FEV1) at Week 12 + 1 Day, Day 85 | 1.32 Liters | Standard Error 0.024 |
| Indacaterol 300 μg | Trough Forced Expiratory Volume in 1 Second (FEV1) at Week 12 + 1 Day, Day 85 | 1.29 Liters | Standard Error 0.024 |
| Placebo to Indacaterol | Trough Forced Expiratory Volume in 1 Second (FEV1) at Week 12 + 1 Day, Day 85 | 1.17 Liters | Standard Error 0.024 |