Chronic Obstructive Pulmonary Disease
Conditions
Keywords
Indacaterol, COPD, salmeterol
Brief summary
This study compared the 14-day bronchodilator efficacy of indacaterol with that of placebo and salmeterol.
Interventions
DRUGIndacaterol
Indacaterol was supplied in powder filled capsules together with a single-dose dry-powder inhaler (SDDPI) device.
DRUGSalmeterol 50 μg
Salmeterol was supplied in the manufacturer's proprietary Diskus inhaler device.
DRUGPlacebo to indacaterol
Placebo to indacaterol was supplied in powder filled capsules together with a single-dose dry-powder inhaler (SDDPI) device.
Placebo to salmeterol was supplied in the manufacturer's proprietary Diskus inhaler device.
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
* 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: 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 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 comorbid 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 2 + 1 Day, Day 15) | 24 hours post-dose at the end of the study (Week 2 + 1 day, Day 15) | 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 salbutamol/albuterol 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 on Day 2. The analysis included baseline FEV1, FEV1 pre-dose and 10-15 minutes post-dose of salbutamol/albuterol during screening, and FEV1 pre-dose and 1 hour post-dose of ipratropium during screening as covariates. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Indacaterol 18.75 μg Patients inhaled indacaterol 18.75 μg once daily in the morning via the Concept1 single-dose dry-powder inhaler (SDDPI). In addition, patients inhaled placebo to salmeterol twice daily, once in the morning and once in the evening, via the manufacturer's proprietary Diskus inhaler. Treatment continued for 2 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. Albuterol via a multi-dose dry-powder inhaler (MDI) was available for rescue use throughout the study. | 89 |
| Indacaterol 37.5 μg Patients inhaled indacaterol 37.5 μg once daily in the morning via the Concept1 single-dose dry-powder inhaler (SDDPI). In addition, patients inhaled placebo to salmeterol twice daily, once in the morning and once in the evening, via the manufacturer's proprietary Diskus inhaler. Treatment continued for 2 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. Albuterol via a multi-dose dry-powder inhaler (MDI) was available for rescue use throughout the study. | 90 |
| Indacaterol 75 μg Patients inhaled indacaterol 75 μg once daily in the morning via the Concept1 single-dose dry-powder inhaler (SDDPI). In addition, patients inhaled placebo to salmeterol twice daily, once in the morning and once in the evening, via the manufacturer's proprietary Diskus inhaler. Treatment continued for 2 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. Albuterol via a multi-dose dry-powder inhaler (MDI) was available for rescue use throughout the study. | 94 |
| Indacaterol 150 μg Patients inhaled indacaterol 150 μg once daily in the morning via the Concept1 single-dose dry-powder inhaler (SDDPI). In addition, patients inhaled placebo to salmeterol twice daily, once in the morning and once in the evening, via the manufacturer's proprietary Diskus inhaler. Treatment continued for 2 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. Albuterol via a multi-dose dry-powder inhaler (MDI) was available for rescue use throughout the study. | 92 |
| Salmeterol 50 μg Patients inhaled salmeterol 50 μg twice daily, once in the morning and once in the evening, via the manufacturer's proprietary Diskus inhaler. In addition, patients inhaled placebo to indacaterol once daily in the morning via the Concept1 single-dose dry-powder inhaler (SDDPI). Treatment continued for 2 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. Albuterol via a multi-dose dry-powder inhaler (MDI) was available for rescue use throughout the study. | 91 |
| Placebo Patients inhaled placebo to indacaterol once daily in the morning via the Concept1 single-dose dry-powder inhaler (SDDPI). In addition, patients inhaled placebo to salmeterol twice daily, once in the morning and once in the evening, via the manufacturer's proprietary Diskus inhaler. Treatment continued for 2 weeks. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. Albuterol via a multi-dose dry-powder inhaler (MDI) was available for rescue use throughout the study. | 91 |
| Total | 547 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Abnormal test procedure result(s) | 2 | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Adverse Event | 5 | 1 | 1 | 0 | 0 | 1 |
| Overall Study | Lost to Follow-up | 1 | 1 | 0 | 0 | 1 | 0 |
| Overall Study | Protocol deviation | 0 | 1 | 0 | 0 | 1 | 0 |
| Overall Study | Subject withdrew consent | 0 | 1 | 1 | 1 | 0 | 2 |
Baseline characteristics
| Characteristic | Indacaterol 18.75 μg | Indacaterol 37.5 μg | Indacaterol 75 μg | Indacaterol 150 μg | Salmeterol 50 μg | Placebo | Total |
|---|---|---|---|---|---|---|---|
| Age Continuous | 62.8 years STANDARD_DEVIATION 8.95 | 61.9 years STANDARD_DEVIATION 9.61 | 62.6 years STANDARD_DEVIATION 9.3 | 62.3 years STANDARD_DEVIATION 9.5 | 62.4 years STANDARD_DEVIATION 9.52 | 63.6 years STANDARD_DEVIATION 8.44 | 62.6 years STANDARD_DEVIATION 9.2 |
| Sex: Female, Male Female | 39 Participants | 43 Participants | 40 Participants | 39 Participants | 47 Participants | 43 Participants | 251 Participants |
| Sex: Female, Male Male | 50 Participants | 47 Participants | 54 Participants | 53 Participants | 44 Participants | 48 Participants | 296 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 1 / 89 | 7 / 90 | 8 / 94 | 2 / 92 | 4 / 91 | 9 / 91 |
| serious Total, serious adverse events | 1 / 89 | 0 / 90 | 0 / 94 | 1 / 92 | 0 / 91 | 3 / 91 |
Outcome results
Primary
Trough Forced Expiratory Volume in 1 Second (FEV1) 24 Hours Post-dose at the End of the Study (Week 2 + 1 Day, Day 15)
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 salbutamol/albuterol 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 2 + 1 day, Day 15)
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 18.75 μg | Trough Forced Expiratory Volume in 1 Second (FEV1) 24 Hours Post-dose at the End of the Study (Week 2 + 1 Day, Day 15) | 1.35 Liters | Standard Error 0.02 |
| Indacaterol 37.5 μg | Trough Forced Expiratory Volume in 1 Second (FEV1) 24 Hours Post-dose at the End of the Study (Week 2 + 1 Day, Day 15) | 1.38 Liters | Standard Error 0.019 |
| Indacaterol 75 μg | Trough Forced Expiratory Volume in 1 Second (FEV1) 24 Hours Post-dose at the End of the Study (Week 2 + 1 Day, Day 15) | 1.38 Liters | Standard Error 0.019 |
| Indacaterol 150 μg | Trough Forced Expiratory Volume in 1 Second (FEV1) 24 Hours Post-dose at the End of the Study (Week 2 + 1 Day, Day 15) | 1.40 Liters | Standard Error 0.019 |
| Salmeterol 50 μg | Trough Forced Expiratory Volume in 1 Second (FEV1) 24 Hours Post-dose at the End of the Study (Week 2 + 1 Day, Day 15) | 1.39 Liters | Standard Error 0.019 |
| Placebo | Trough Forced Expiratory Volume in 1 Second (FEV1) 24 Hours Post-dose at the End of the Study (Week 2 + 1 Day, Day 15) | 1.28 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 on Day 2. The analysis included baseline FEV1, FEV1 pre-dose and 10-15 minutes post-dose of salbutamol/albuterol 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: 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 18.75 μg | Trough Forced Expiratory Volume in 1 Second (FEV1) 24 Hours Post-dose on Day 2 | 1.33 Liters | Standard Error 0.015 |
| Indacaterol 37.5 μg | Trough Forced Expiratory Volume in 1 Second (FEV1) 24 Hours Post-dose on Day 2 | 1.34 Liters | Standard Error 0.015 |
| Indacaterol 75 μg | Trough Forced Expiratory Volume in 1 Second (FEV1) 24 Hours Post-dose on Day 2 | 1.38 Liters | Standard Error 0.015 |
| Indacaterol 150 μg | Trough Forced Expiratory Volume in 1 Second (FEV1) 24 Hours Post-dose on Day 2 | 1.40 Liters | Standard Error 0.014 |
| Salmeterol 50 μg | Trough Forced Expiratory Volume in 1 Second (FEV1) 24 Hours Post-dose on Day 2 | 1.41 Liters | Standard Error 0.015 |
| Placebo | Trough Forced Expiratory Volume in 1 Second (FEV1) 24 Hours Post-dose on Day 2 | 1.28 Liters | Standard Error 0.015 |