Chronic Obstructive Pulmonary Disease
Conditions
Keywords
COPD, indacaterol, tiotropium
Brief summary
This study compared the effects of a single dose of indacaterol with that of a single dose of tiotropium on inspiratory capacity.
Interventions
Indacaterol was supplied in powder filled capsules together with a single dose dry powder inhaler (SDDPI) device.
DRUGTiotropium 18 μg
Tiotropium was supplied in powder filled capsules together with a single dose dry powder inhaler (SDDPI) device.
DRUGPlacebo
Placebo (matching indacaterol) was supplied in powder filled capsules together with a single dose dry powder inhaler (SDDPI) device.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
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 moderate (as classified by the Global Initiative for Chronic Obstructive Lung Disease \[GOLD\] Guidelines, 2007) chronic obstructive pulmonary disease (COPD) and: 1. Smoking history of at least 10 pack-years. 2. Forced expiratory volume in 1 second (FEV1) \< 80% and ≥ 50% of the predicted normal value. 3. Post-bronchodilator FEV1/Force vital capacity (FVC) \< 0.7.
Exclusion criteria
* Patients who have had a COPD exacerbation requiring systemic glucocorticosteroid treatment 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 alpha-1-antitrypsin deficiency. * Patients with contraindications for tiotropium treatment. * Patients with a history of hypersensitivity to any of the study drugs or to drugs from similar drug classes. Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Peak Inspiratory Capacity Assessed With Spirometry in the 4 Hours After Treatment | 4 hour period following inhalation of study treatment | During the 4 hours following inhalation of the study treatment, inspiratory capacity (IC) was measured with spirometry conducted according to internationally accepted standards. IC was measured 3 times each at 30, 60, 120, 180, and 240 minutes post-dose and the highest value was reported in liters. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Forced Expiratory Volume in 1 Second (FEV1) Standardized (With Respect to Length of Time) Area Under the Curve (AUC) in the 4 Hours After Treatment | 4 hour period following inhalation of study treatment | FEV1 was measured with spirometry conducted according to internationally accepted standards. Measurements were made 30, 60, 120, 180, and 240 minutes post-dose. The standardized AUC FEV1 was calculated as the sum of trapezoids divided by the length of time. |
| Force Vital Capacity (FVC) Standardized (With Respect to Length of Time) Area Under the Curve (AUC) in the 4 Hours After Treatment | 4 hour period following inhalation of study treatment | FVC was measured with spirometry conducted according to internationally accepted standards. Measurements were made 30, 60, 120, 180, and 240 minutes post-dose. The standardized AUC FEV1 was calculated as the sum of trapezoids divided by the length of time. |
Countries
Italy
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Entire Study Population The entire study population includes the 3 groups of patients who received indacaterol 150 μg, tiotropium 18 μg, and placebo (matching indacaterol) once each in 1 of 3 different orders in this crossover study. All treatments were delivered via a single dose dry powder inhaler (SDDPI). The short-acting β2-agonist salbutamol was available for rescue use throughout the study. | 54 |
| Total | 54 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Treatment Period 1 | Subject withdrew consent | 2 | 0 | 0 |
| Treatment Period 2 | Protocol Violation | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Entire Study Population |
|---|---|
| Age, Continuous | 69.3 years STANDARD_DEVIATION 9.2 |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 49 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 | 0 / 54 | 0 / 52 | 0 / 51 |
| serious Total, serious adverse events | 0 / 54 | 0 / 52 | 0 / 51 |
Outcome results
Primary
Peak Inspiratory Capacity Assessed With Spirometry in the 4 Hours After Treatment
During the 4 hours following inhalation of the study treatment, inspiratory capacity (IC) was measured with spirometry conducted according to internationally accepted standards. IC was measured 3 times each at 30, 60, 120, 180, and 240 minutes post-dose and the highest value was reported in liters.
Time frame: 4 hour period following inhalation of study treatment
Population: Per protocol population: All randomized patients who received all the study drugs and had at least 1 post-dose inspiratory capacity measurement within 4 hours after inhalation in each treatment period and who were compliant with the protocol and without any major deviation likely to affect the analysis of pulmonary function measurements.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Indacaterol 150 μg | Peak Inspiratory Capacity Assessed With Spirometry in the 4 Hours After Treatment | 2.705 Liters | Standard Deviation 0.676 |
| Tiotropium 18 μg | Peak Inspiratory Capacity Assessed With Spirometry in the 4 Hours After Treatment | 2.630 Liters | Standard Deviation 0.601 |
| Placebo | Peak Inspiratory Capacity Assessed With Spirometry in the 4 Hours After Treatment | 2.557 Liters | Standard Deviation 0.561 |
Secondary
Forced Expiratory Volume in 1 Second (FEV1) Standardized (With Respect to Length of Time) Area Under the Curve (AUC) in the 4 Hours After Treatment
FEV1 was measured with spirometry conducted according to internationally accepted standards. Measurements were made 30, 60, 120, 180, and 240 minutes post-dose. The standardized AUC FEV1 was calculated as the sum of trapezoids divided by the length of time.
Time frame: 4 hour period following inhalation of study treatment
Population: Intent-to-treat population: All randomized patients who received all the study drugs and had at least 1 post-dose inspiratory capacity measurement within 4 hours after inhalation in each treatment period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Indacaterol 150 μg | Forced Expiratory Volume in 1 Second (FEV1) Standardized (With Respect to Length of Time) Area Under the Curve (AUC) in the 4 Hours After Treatment | 1.744 Liters | Standard Deviation 0.419 |
| Tiotropium 18 μg | Forced Expiratory Volume in 1 Second (FEV1) Standardized (With Respect to Length of Time) Area Under the Curve (AUC) in the 4 Hours After Treatment | 1.767 Liters | Standard Deviation 0.449 |
| Placebo | Forced Expiratory Volume in 1 Second (FEV1) Standardized (With Respect to Length of Time) Area Under the Curve (AUC) in the 4 Hours After Treatment | 1.642 Liters | Standard Deviation 0.409 |
Secondary
Force Vital Capacity (FVC) Standardized (With Respect to Length of Time) Area Under the Curve (AUC) in the 4 Hours After Treatment
FVC was measured with spirometry conducted according to internationally accepted standards. Measurements were made 30, 60, 120, 180, and 240 minutes post-dose. The standardized AUC FEV1 was calculated as the sum of trapezoids divided by the length of time.
Time frame: 4 hour period following inhalation of study treatment
Population: Intent-to-treat population: All randomized patients who received all the study drugs and had at least 1 post-dose inspiratory capacity measurement within 4 hours after inhalation in each treatment period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Indacaterol 150 μg | Force Vital Capacity (FVC) Standardized (With Respect to Length of Time) Area Under the Curve (AUC) in the 4 Hours After Treatment | 3.140 Liters | Standard Deviation 0.7 |
| Tiotropium 18 μg | Force Vital Capacity (FVC) Standardized (With Respect to Length of Time) Area Under the Curve (AUC) in the 4 Hours After Treatment | 3.176 Liters | Standard Deviation 0.788 |
| Placebo | Force Vital Capacity (FVC) Standardized (With Respect to Length of Time) Area Under the Curve (AUC) in the 4 Hours After Treatment | 3.048 Liters | Standard Deviation 0.753 |