Chronic Obstructive Pulmonary Disease (COPD)
Conditions
Keywords
respiratory, dyspnea, breathlessness, COPD, indacaterol, long-acting β2-agonist
Brief summary
This study compared the safety and efficacy of indacaterol 150 µg taken once daily (o.d.) versus salmeterol 50 µg taken twice daily (b.i.d) in patients 40 years old or older with chronic obstructive pulmonary disease.
Interventions
Indacaterol 150 μg was provided in powder-filled capsules with a single-dose dry-powder inhaler (SDDPI).
DRUGSalmeterol 50 µg
Salmeterol 50 μg was provided in the manufacturer's proprietary multi-dose dry-powder inhaler (MDDPI, \[DISKUS\]).
DRUGPlacebo to indacaterol
Placebo to indacaterol was provided in powder-filled capsules with a single-dose dry-powder inhaler (SDDPI).
Placebo to salmeterol was provided in the manufacturer's proprietary multi-dose dry-powder inhaler (MDDPI, \[DISKUS\]).
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 GOLD Guidelines, 2007) 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 at screening * Post-bronchodilator FEV1/FVC (forced vital capacity) \< 70% at screening
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 h 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 (Fridericia'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 |
|---|---|---|
| Forced Expiratory Volume in 1 Second (FEV1) Standardized (With Respect to Time) Area Under the Curve (AUC) From 5 Minutes to 11 Hours 45 Minutes Post-dose at the End of the Study (Week 12, Day 84) | From 5 minutes to 11 hours 45 minutes post-dose at the end of the study (Week 12, Day 84) | FEV1 was measured with spirometry conducted according to internationally accepted standards. Measurements were made at 5 and 30 minutes; 1, 2, 3, 4, and 8 hours; 11 hours 10 minutes and 11 hours 45 minutes post-dose at the end of the study (Week 12, Day 84). Standardized FEV1 AUC was calculated by the trapezoidal rule. The analysis included baseline FEV1 and FEV1 pre-dose and 10-15 minutes post-dose of salbutamol/albuterol during screening as covariates. |
Secondary
| 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 and FEV1 pre-dose and 10-15 minutes post-dose of salbutamol/albuterol during screening as covariates. |
Countries
Czechia, Germany, Hungary, India, Slovakia, Spain, Turkey (Türkiye), United States
Participant flow
Pre-assignment details
Out of total 1123 randomized patients, two patients withdrew from study prior to exposure to study drug.
Participants by arm
| Arm | Count |
|---|---|
| Indacaterol 150 μg Patients inhaled indacaterol 150 μg once daily in the morning between 8:00 and 11:00 AM via a single-dose dry-powder inhaler (SDDPI) for 12 weeks. Patients also inhaled placebo to salmeterol twice daily, once in the morning between 8:00 and 11:00 AM and once in the evening between 8:00 and 11:00 PM via the manufacturer's proprietary multi-dose dry-powder inhaler (MDDPI, \[DISKUS\]) 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. | 559 |
| Salmeterol 50 μg Patients inhaled salmeterol 50 μg twice daily, once in the morning between 8:00 and 11:00 AM and once in the evening between 8:00 and 11:00 PM via the manufacturer's proprietary multi-dose dry-powder inhaler (MDDPI, \[DISKUS\]) for 12 weeks. Patients also inhaled placebo to indacaterol once daily in the morning between 8:00 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. | 562 |
| Total | 1,121 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Abnormal laboratory value(s) | 2 | 0 |
| Overall Study | Abnormal test procedure result(s) | 1 | 1 |
| Overall Study | Administrative problems | 1 | 2 |
| Overall Study | Adverse Event | 20 | 12 |
| Overall Study | Death | 2 | 1 |
| Overall Study | Lack of Efficacy | 2 | 2 |
| Overall Study | Lost to Follow-up | 9 | 3 |
| Overall Study | Protocol deviation | 3 | 6 |
| Overall Study | Withdrawal by Subject | 9 | 13 |
Baseline characteristics
| Characteristic | Indacaterol 150 μg | Salmeterol 50 μg | Total |
|---|---|---|---|
| Age Continuous | 62.4 years STANDARD_DEVIATION 8.86 | 63.2 years STANDARD_DEVIATION 8.69 | 62.8 years STANDARD_DEVIATION 8.78 |
| Sex: Female, Male Female | 189 Participants | 147 Participants | 336 Participants |
| Sex: Female, Male Male | 370 Participants | 415 Participants | 785 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 559 | 0 / 562 |
| serious Total, serious adverse events | 20 / 559 | 16 / 562 |
Outcome results
Primary
Forced Expiratory Volume in 1 Second (FEV1) Standardized (With Respect to Time) Area Under the Curve (AUC) From 5 Minutes to 11 Hours 45 Minutes Post-dose at the End of the Study (Week 12, Day 84)
FEV1 was measured with spirometry conducted according to internationally accepted standards. Measurements were made at 5 and 30 minutes; 1, 2, 3, 4, and 8 hours; 11 hours 10 minutes and 11 hours 45 minutes post-dose at the end of the study (Week 12, Day 84). Standardized FEV1 AUC was calculated by the trapezoidal rule. The analysis included baseline FEV1 and FEV1 pre-dose and 10-15 minutes post-dose of salbutamol/albuterol during screening as covariates.
Time frame: From 5 minutes to 11 hours 45 minutes post-dose at the 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 150 μg | Forced Expiratory Volume in 1 Second (FEV1) Standardized (With Respect to Time) Area Under the Curve (AUC) From 5 Minutes to 11 Hours 45 Minutes Post-dose at the End of the Study (Week 12, Day 84) | 1.47 Liters | Standard Error 0.009 |
| Salmeterol 50 μg | Forced Expiratory Volume in 1 Second (FEV1) Standardized (With Respect to Time) Area Under the Curve (AUC) From 5 Minutes to 11 Hours 45 Minutes Post-dose at the End of the Study (Week 12, Day 84) | 1.41 Liters | Standard Error 0.01 |
Secondary
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 and FEV1 pre-dose and 10-15 minutes post-dose of salbutamol/albuterol 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 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) | 1.41 Liters | Standard Error 0.009 |
| Salmeterol 50 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) | 1.35 Liters | Standard Error 0.01 |