Chronic Obstructive Pulmonary Disease
Conditions
Keywords
chronic obstructive pulmonary disease, COPD, indacaterol
Brief summary
This study was designed to provide 12 weeks efficacy and safety data of the 150 μg once-daily (od) dose of indacaterol in chronic obstructive pulmonary disease (COPD).
Interventions
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
• Male or female patients aged 40 years or over with moderate to severe chronic obstructive pulmonary disease (COPD) plus * 20 pack-year smoking history * Signed informed consent * Post-bronchodilator forced expiratory volume in 1 second )FEV1) ≥ 30% and \< 80% predicted FEV1/FVC (forced vital capacity) \< 70%
Exclusion criteria
include: * History of asthma * Prior exposure to indacaterol * Active cancer or history of cancer * Patients with concomitant pulmonary disease * Patients with diabetes Type I or uncontrolled diabetes Type II * Patients with a history of long QT syndrome or whose QTc interval (Bazett's) measured at screening or randomization is prolonged * 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 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 30 minutes post-dose of salbutamol during screening, and FEV1 pre-dose and 1 hour post-dose of ipratropium during screening as covariates. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Trough Forced Expiratory Volume in 1 Second (FEV1) 24 Hours Post-dose on Day 2 | 24 hours post-dose on Day 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 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 1 hour post-dose of ipratropium during screening as covariates. |
Countries
Belgium, New Zealand, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Indacaterol 150 μg Patients inhaled indacaterol 150 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. | 211 |
| 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. | 205 |
| Total | 416 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Abnormal test procedure result(s) | 0 | 1 |
| Overall Study | Administrative problems | 3 | 0 |
| Overall Study | Adverse Event | 6 | 3 |
| Overall Study | Death | 0 | 1 |
| Overall Study | Lack of Efficacy | 1 | 6 |
| Overall Study | Lost to Follow-up | 3 | 2 |
| Overall Study | Not stated | 0 | 1 |
| Overall Study | Protocol Deviation | 7 | 9 |
| Overall Study | Withdrawal by Subject | 5 | 4 |
Baseline characteristics
| Characteristic | Indacaterol 150 μg | Placebo to Indacaterol | Total |
|---|---|---|---|
| Age Continuous | 62.9 years STANDARD_DEVIATION 9.89 | 63.2 years STANDARD_DEVIATION 9.62 | 63.0 years STANDARD_DEVIATION 9.75 |
| Sex: Female, Male Female | 103 Participants | 95 Participants | 198 Participants |
| Sex: Female, Male Male | 108 Participants | 110 Participants | 218 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 30 / 211 | 37 / 205 |
| serious Total, serious adverse events | 7 / 211 | 5 / 205 |
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 30 minutes post-dose of salbutamol during screening, and FEV1 pre-dose and 1 hour 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: Intent-to-treat population: 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 150 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) | 1.48 Liters | Standard Error 0.018 |
| 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) | 1.35 Liters | Standard Error 0.019 |
Secondary
Trough Forced Expiratory Volume in 1 Second (FEV1) 24 Hours Post-dose on Day 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 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 1 hour post-dose of ipratropium during screening as covariates.
Time frame: 24 hours post-dose on Day 2
Population: Intent-to-treat population: All randomized patients who received at least 1 dose of study drug. FEV1 data taken within 6 h of rescue medication was excluded from this analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Indacaterol 150 μg | Trough Forced Expiratory Volume in 1 Second (FEV1) 24 Hours Post-dose on Day 2 | 1.47 Liters | Standard Error 0.014 |
| Placebo to Indacaterol | Trough Forced Expiratory Volume in 1 Second (FEV1) 24 Hours Post-dose on Day 2 | 1.38 Liters | Standard Error 0.014 |