Chronic Obstructive Pulmonary Disease
Conditions
Keywords
chronic obstructive pulmonary disease, COPD, QAB149, indacaterol, long acting β2-agonist
Brief summary
The study was designed to obtain data about the efficacy and safety of 3 doses of indacaterol (150, 300, and 600 µg) in Japanese patients with chronic obstructive pulmonary disease (COPD) so that optimal dose(s) could be chosen for testing in later studies.
Interventions
Indacaterol 150 μg was provided in powder filled capsules with a single dose dry powder inhaler (SDDPI).
Indacaterol 300 μg was provided in powder filled capsules with a single dose dry powder inhaler (SDDPI).
DRUGPlacebo
Placebo to indacaterol was provided in powder filled capsules with a single dose dry powder inhaler (SDDPI).
Sponsors
Novartis
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Male and female Japanese aged 40 to 75 years old * Moderate to severe chronic obstructive pulmonary disease (COPD) with smoking history of at least 20 pack years
Exclusion criteria
* History of hospitalization for COPD exacerbation within past 6 months * Use of long-term oxygen therapy * History of asthma * Respiratory tract infection within past 1 month * Consistently very high or low blood sugar * Clinically abnormal laboratory values or significant condition * History of heart failure or heart attack within past 6 months * History of long QT syndrome or long QT interval in electrocardiogram recorded at screening 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 22 to 24 Hours Post-dose on Day 2 | From 22 to 24 hours post-dose on Day 2 | FEV1 was measured with spirometry conducted according to internationally accepted standards. Measurements were made in each treatment period at 22, 23, and 24 hours post-dose on Day 2. Standardized FEV1 AUC was calculated by the trapezoidal rule. The analysis included patient, period, and treatment group as fixed effects and baseline FEV1 prior to drug administration in the treatment period as a covariate. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Peak Forced Expiratory Volume in 1 Second (FEV1) From 5 Minutes to 4 Hours Post-dose on Day 1 | From 5 minutes to 4 hours post-dose on Day 1 | FEV1 was measured with spirometry conducted according to internationally accepted standards. Measurements were made in each treatment period at 5, 15, and 30 minutes and 1, 2, and 4 hours post-dose on Day 1. The analysis included baseline FEV1 prior to drug administration in the treatment period as a covariate. |
| Forced Expiratory Volume in 1 Second (FEV1) by Time Point From 5 Minutes to 12 Hours Post-dose on Day 1 and From 22 to 24 Hours Post-dose on Day 2 | From 5 minutes to 12 hours post-dose on Day 1 and from 22 to 24 hours post-dose on Day 2 | FEV1 was measured with spirometry conducted according to internationally accepted standards. Measurements were made in each treatment period at 5, 15, and 30 minutes and 1, 2, 4, 8, and 12 hours on Day 1 and 22, 23, and 24 hours on Day 2. The analysis included baseline FEV1 prior to drug administration in the treatment period as a covariate. |
| Forced Expiratory Volume in 1 Second (FEV1) Standardized (With Respect to Time) Area Under the Curve (AUC) From 5 Minutes to 12 Hours Post-dose on Day 1 and From 22 to 24 Hours Post-dose on Day 2 | From 5 minutes to 12 hours post-dose on Day 1 and from 22 to 24 hours post-dose on Day 2 | FEV1 was measured with spirometry conducted according to internationally accepted standards. Measurements were made in each treatment period at 5, 15, and 30 minutes and 1, 2, 4, 8, and 12 hours on Day 1 and 22, 23, and 24 hours on Day 2. Standardized FEV1 AUC was calculated by the trapezoidal rule. The analysis included baseline FEV1 prior to drug administration in the treatment period as a covariate. |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Entire Study Population The entire study population included all 4 treatment groups who received indacaterol 150 µg, 300 µg, and 600 µg and placebo via a single dose dry powder inhaler (SDDPI) in 4 different sequences. Two capsules of study medication were inhaled in the morning between 8:00 and 10:00 am on Day 1 of each treatment period. Patients received each treatment only once. The short-acting β2-agonist salbutamol was available for rescue use throughout the study. | 50 |
| Total | 50 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Treatment Period 1 | Subject no longer needs study drug | 0 | 0 | 0 | 1 |
| Treatment Period 1 | Subject withdrew consent | 1 | 0 | 0 | 0 |
| Treatment Period 2 | Subject withdrew consent | 1 | 0 | 0 | 0 |
| Treatment Period 3 | Adverse Event | 0 | 0 | 0 | 1 |
| Treatment Period 3 | Subject withdrew consent | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Entire Study Population |
|---|---|
| Age Continuous | 67.2 years STANDARD_DEVIATION 5.94 |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 46 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 1 / 47 | 4 / 48 | 4 / 47 | 5 / 48 |
| serious Total, serious adverse events | 0 / 47 | 1 / 48 | 0 / 47 | 0 / 48 |
Outcome results
Primary
Forced Expiratory Volume in 1 Second (FEV1) Standardized (With Respect to Time) Area Under the Curve (AUC) From 22 to 24 Hours Post-dose on Day 2
FEV1 was measured with spirometry conducted according to internationally accepted standards. Measurements were made in each treatment period at 22, 23, and 24 hours post-dose on Day 2. Standardized FEV1 AUC was calculated by the trapezoidal rule. The analysis included patient, period, and treatment group as fixed effects and baseline FEV1 prior to drug administration in the treatment period as a covariate.
Time frame: From 22 to 24 hours post-dose on Day 2
Population: Modified intent-to-treat (modified ITT) population: All randomized patients who received at least 1 dose of study drug. Patients were included in the analysis if they had at least 1 FEV1 value at 22, 23, or 24 hours post-dose, and the data were not collected within 6 hours after the use of rescue medication.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Indacaterol 600 μg | Forced Expiratory Volume in 1 Second (FEV1) Standardized (With Respect to Time) Area Under the Curve (AUC) From 22 to 24 Hours Post-dose on Day 2 | 1.49 Liters | Standard Error 0.01 |
| Indacaterol 300 µg | Forced Expiratory Volume in 1 Second (FEV1) Standardized (With Respect to Time) Area Under the Curve (AUC) From 22 to 24 Hours Post-dose on Day 2 | 1.48 Liters | Standard Error 0.01 |
| Indacaterol 150 µg | Forced Expiratory Volume in 1 Second (FEV1) Standardized (With Respect to Time) Area Under the Curve (AUC) From 22 to 24 Hours Post-dose on Day 2 | 1.45 Liters | Standard Error 0.01 |
| Placebo | Forced Expiratory Volume in 1 Second (FEV1) Standardized (With Respect to Time) Area Under the Curve (AUC) From 22 to 24 Hours Post-dose on Day 2 | 1.33 Liters | Standard Error 0.01 |
Secondary
Forced Expiratory Volume in 1 Second (FEV1) by Time Point From 5 Minutes to 12 Hours Post-dose on Day 1 and From 22 to 24 Hours Post-dose on Day 2
FEV1 was measured with spirometry conducted according to internationally accepted standards. Measurements were made in each treatment period at 5, 15, and 30 minutes and 1, 2, 4, 8, and 12 hours on Day 1 and 22, 23, and 24 hours on Day 2. The analysis included baseline FEV1 prior to drug administration in the treatment period as a covariate.
Time frame: From 5 minutes to 12 hours post-dose on Day 1 and from 22 to 24 hours post-dose on Day 2
Population: Modified intent-to-treat (modified ITT) population: All randomized patients who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Indacaterol 600 μg | Forced Expiratory Volume in 1 Second (FEV1) by Time Point From 5 Minutes to 12 Hours Post-dose on Day 1 and From 22 to 24 Hours Post-dose on Day 2 | 8 hour | 1.50 Liters |
| Indacaterol 600 μg | Forced Expiratory Volume in 1 Second (FEV1) by Time Point From 5 Minutes to 12 Hours Post-dose on Day 1 and From 22 to 24 Hours Post-dose on Day 2 | 4 hours | 1.53 Liters |
| Indacaterol 600 μg | Forced Expiratory Volume in 1 Second (FEV1) by Time Point From 5 Minutes to 12 Hours Post-dose on Day 1 and From 22 to 24 Hours Post-dose on Day 2 | 1 hour | 1.51 Liters |
| Indacaterol 600 μg | Forced Expiratory Volume in 1 Second (FEV1) by Time Point From 5 Minutes to 12 Hours Post-dose on Day 1 and From 22 to 24 Hours Post-dose on Day 2 | 24 hours | 1.51 Liters |
| Indacaterol 600 μg | Forced Expiratory Volume in 1 Second (FEV1) by Time Point From 5 Minutes to 12 Hours Post-dose on Day 1 and From 22 to 24 Hours Post-dose on Day 2 | 2 hours | 1.55 Liters |
| Indacaterol 600 μg | Forced Expiratory Volume in 1 Second (FEV1) by Time Point From 5 Minutes to 12 Hours Post-dose on Day 1 and From 22 to 24 Hours Post-dose on Day 2 | 15 minutes | 1.50 Liters |
| Indacaterol 600 μg | Forced Expiratory Volume in 1 Second (FEV1) by Time Point From 5 Minutes to 12 Hours Post-dose on Day 1 and From 22 to 24 Hours Post-dose on Day 2 | 5 minutes | 1.47 Liters |
| Indacaterol 600 μg | Forced Expiratory Volume in 1 Second (FEV1) by Time Point From 5 Minutes to 12 Hours Post-dose on Day 1 and From 22 to 24 Hours Post-dose on Day 2 | 23 hours | 1.51 Liters |
| Indacaterol 600 μg | Forced Expiratory Volume in 1 Second (FEV1) by Time Point From 5 Minutes to 12 Hours Post-dose on Day 1 and From 22 to 24 Hours Post-dose on Day 2 | 12 hours | 1.49 Liters |
| Indacaterol 600 μg | Forced Expiratory Volume in 1 Second (FEV1) by Time Point From 5 Minutes to 12 Hours Post-dose on Day 1 and From 22 to 24 Hours Post-dose on Day 2 | 30 minutes | 1.52 Liters |
| Indacaterol 600 μg | Forced Expiratory Volume in 1 Second (FEV1) by Time Point From 5 Minutes to 12 Hours Post-dose on Day 1 and From 22 to 24 Hours Post-dose on Day 2 | 22 hours | 1.47 Liters |
| Indacaterol 300 µg | Forced Expiratory Volume in 1 Second (FEV1) by Time Point From 5 Minutes to 12 Hours Post-dose on Day 1 and From 22 to 24 Hours Post-dose on Day 2 | 23 hours | 1.49 Liters |
| Indacaterol 300 µg | Forced Expiratory Volume in 1 Second (FEV1) by Time Point From 5 Minutes to 12 Hours Post-dose on Day 1 and From 22 to 24 Hours Post-dose on Day 2 | 5 minutes | 1.48 Liters |
| Indacaterol 300 µg | Forced Expiratory Volume in 1 Second (FEV1) by Time Point From 5 Minutes to 12 Hours Post-dose on Day 1 and From 22 to 24 Hours Post-dose on Day 2 | 15 minutes | 1.50 Liters |
| Indacaterol 300 µg | Forced Expiratory Volume in 1 Second (FEV1) by Time Point From 5 Minutes to 12 Hours Post-dose on Day 1 and From 22 to 24 Hours Post-dose on Day 2 | 30 minutes | 1.52 Liters |
| Indacaterol 300 µg | Forced Expiratory Volume in 1 Second (FEV1) by Time Point From 5 Minutes to 12 Hours Post-dose on Day 1 and From 22 to 24 Hours Post-dose on Day 2 | 1 hour | 1.51 Liters |
| Indacaterol 300 µg | Forced Expiratory Volume in 1 Second (FEV1) by Time Point From 5 Minutes to 12 Hours Post-dose on Day 1 and From 22 to 24 Hours Post-dose on Day 2 | 2 hours | 1.54 Liters |
| Indacaterol 300 µg | Forced Expiratory Volume in 1 Second (FEV1) by Time Point From 5 Minutes to 12 Hours Post-dose on Day 1 and From 22 to 24 Hours Post-dose on Day 2 | 4 hours | 1.53 Liters |
| Indacaterol 300 µg | Forced Expiratory Volume in 1 Second (FEV1) by Time Point From 5 Minutes to 12 Hours Post-dose on Day 1 and From 22 to 24 Hours Post-dose on Day 2 | 22 hours | 1.46 Liters |
| Indacaterol 300 µg | Forced Expiratory Volume in 1 Second (FEV1) by Time Point From 5 Minutes to 12 Hours Post-dose on Day 1 and From 22 to 24 Hours Post-dose on Day 2 | 8 hour | 1.51 Liters |
| Indacaterol 300 µg | Forced Expiratory Volume in 1 Second (FEV1) by Time Point From 5 Minutes to 12 Hours Post-dose on Day 1 and From 22 to 24 Hours Post-dose on Day 2 | 24 hours | 1.50 Liters |
| Indacaterol 300 µg | Forced Expiratory Volume in 1 Second (FEV1) by Time Point From 5 Minutes to 12 Hours Post-dose on Day 1 and From 22 to 24 Hours Post-dose on Day 2 | 12 hours | 1.47 Liters |
| Indacaterol 150 µg | Forced Expiratory Volume in 1 Second (FEV1) by Time Point From 5 Minutes to 12 Hours Post-dose on Day 1 and From 22 to 24 Hours Post-dose on Day 2 | 12 hours | 1.44 Liters |
| Indacaterol 150 µg | Forced Expiratory Volume in 1 Second (FEV1) by Time Point From 5 Minutes to 12 Hours Post-dose on Day 1 and From 22 to 24 Hours Post-dose on Day 2 | 23 hours | 1.46 Liters |
| Indacaterol 150 µg | Forced Expiratory Volume in 1 Second (FEV1) by Time Point From 5 Minutes to 12 Hours Post-dose on Day 1 and From 22 to 24 Hours Post-dose on Day 2 | 4 hours | 1.48 Liters |
| Indacaterol 150 µg | Forced Expiratory Volume in 1 Second (FEV1) by Time Point From 5 Minutes to 12 Hours Post-dose on Day 1 and From 22 to 24 Hours Post-dose on Day 2 | 30 minutes | 1.49 Liters |
| Indacaterol 150 µg | Forced Expiratory Volume in 1 Second (FEV1) by Time Point From 5 Minutes to 12 Hours Post-dose on Day 1 and From 22 to 24 Hours Post-dose on Day 2 | 5 minutes | 1.46 Liters |
| Indacaterol 150 µg | Forced Expiratory Volume in 1 Second (FEV1) by Time Point From 5 Minutes to 12 Hours Post-dose on Day 1 and From 22 to 24 Hours Post-dose on Day 2 | 22 hours | 1.43 Liters |
| Indacaterol 150 µg | Forced Expiratory Volume in 1 Second (FEV1) by Time Point From 5 Minutes to 12 Hours Post-dose on Day 1 and From 22 to 24 Hours Post-dose on Day 2 | 1 hour | 1.49 Liters |
| Indacaterol 150 µg | Forced Expiratory Volume in 1 Second (FEV1) by Time Point From 5 Minutes to 12 Hours Post-dose on Day 1 and From 22 to 24 Hours Post-dose on Day 2 | 24 hours | 1.47 Liters |
| Indacaterol 150 µg | Forced Expiratory Volume in 1 Second (FEV1) by Time Point From 5 Minutes to 12 Hours Post-dose on Day 1 and From 22 to 24 Hours Post-dose on Day 2 | 2 hours | 1.51 Liters |
| Indacaterol 150 µg | Forced Expiratory Volume in 1 Second (FEV1) by Time Point From 5 Minutes to 12 Hours Post-dose on Day 1 and From 22 to 24 Hours Post-dose on Day 2 | 8 hour | 1.46 Liters |
| Indacaterol 150 µg | Forced Expiratory Volume in 1 Second (FEV1) by Time Point From 5 Minutes to 12 Hours Post-dose on Day 1 and From 22 to 24 Hours Post-dose on Day 2 | 15 minutes | 1.49 Liters |
| Placebo | Forced Expiratory Volume in 1 Second (FEV1) by Time Point From 5 Minutes to 12 Hours Post-dose on Day 1 and From 22 to 24 Hours Post-dose on Day 2 | 30 minutes | 1.35 Liters |
| Placebo | Forced Expiratory Volume in 1 Second (FEV1) by Time Point From 5 Minutes to 12 Hours Post-dose on Day 1 and From 22 to 24 Hours Post-dose on Day 2 | 4 hours | 1.35 Liters |
| Placebo | Forced Expiratory Volume in 1 Second (FEV1) by Time Point From 5 Minutes to 12 Hours Post-dose on Day 1 and From 22 to 24 Hours Post-dose on Day 2 | 8 hour | 1.30 Liters |
| Placebo | Forced Expiratory Volume in 1 Second (FEV1) by Time Point From 5 Minutes to 12 Hours Post-dose on Day 1 and From 22 to 24 Hours Post-dose on Day 2 | 15 minutes | 1.36 Liters |
| Placebo | Forced Expiratory Volume in 1 Second (FEV1) by Time Point From 5 Minutes to 12 Hours Post-dose on Day 1 and From 22 to 24 Hours Post-dose on Day 2 | 22 hours | 1.29 Liters |
| Placebo | Forced Expiratory Volume in 1 Second (FEV1) by Time Point From 5 Minutes to 12 Hours Post-dose on Day 1 and From 22 to 24 Hours Post-dose on Day 2 | 23 hours | 1.33 Liters |
| Placebo | Forced Expiratory Volume in 1 Second (FEV1) by Time Point From 5 Minutes to 12 Hours Post-dose on Day 1 and From 22 to 24 Hours Post-dose on Day 2 | 5 minutes | 1.36 Liters |
| Placebo | Forced Expiratory Volume in 1 Second (FEV1) by Time Point From 5 Minutes to 12 Hours Post-dose on Day 1 and From 22 to 24 Hours Post-dose on Day 2 | 12 hours | 1.30 Liters |
| Placebo | Forced Expiratory Volume in 1 Second (FEV1) by Time Point From 5 Minutes to 12 Hours Post-dose on Day 1 and From 22 to 24 Hours Post-dose on Day 2 | 1 hour | 1.36 Liters |
| Placebo | Forced Expiratory Volume in 1 Second (FEV1) by Time Point From 5 Minutes to 12 Hours Post-dose on Day 1 and From 22 to 24 Hours Post-dose on Day 2 | 2 hours | 1.36 Liters |
| Placebo | Forced Expiratory Volume in 1 Second (FEV1) by Time Point From 5 Minutes to 12 Hours Post-dose on Day 1 and From 22 to 24 Hours Post-dose on Day 2 | 24 hours | 1.35 Liters |
Secondary
Forced Expiratory Volume in 1 Second (FEV1) Standardized (With Respect to Time) Area Under the Curve (AUC) From 5 Minutes to 12 Hours Post-dose on Day 1 and From 22 to 24 Hours Post-dose on Day 2
FEV1 was measured with spirometry conducted according to internationally accepted standards. Measurements were made in each treatment period at 5, 15, and 30 minutes and 1, 2, 4, 8, and 12 hours on Day 1 and 22, 23, and 24 hours on Day 2. Standardized FEV1 AUC was calculated by the trapezoidal rule. The analysis included baseline FEV1 prior to drug administration in the treatment period as a covariate.
Time frame: From 5 minutes to 12 hours post-dose on Day 1 and from 22 to 24 hours post-dose on Day 2
Population: Modified intent-to-treat (modified ITT) population: All randomized patients who received at least 1 dose of study drug. Patients were included in the analysis if they had at least 1 FEV1 value at 22, 23, or 24 hours post-dose, and the data were not collected within 6 hours after the use of rescue medication.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Indacaterol 600 μg | Forced Expiratory Volume in 1 Second (FEV1) Standardized (With Respect to Time) Area Under the Curve (AUC) From 5 Minutes to 12 Hours Post-dose on Day 1 and From 22 to 24 Hours Post-dose on Day 2 | 1.50 Liters | Standard Error 0.009 |
| Indacaterol 300 µg | Forced Expiratory Volume in 1 Second (FEV1) Standardized (With Respect to Time) Area Under the Curve (AUC) From 5 Minutes to 12 Hours Post-dose on Day 1 and From 22 to 24 Hours Post-dose on Day 2 | 1.49 Liters | Standard Error 0.009 |
| Indacaterol 150 µg | Forced Expiratory Volume in 1 Second (FEV1) Standardized (With Respect to Time) Area Under the Curve (AUC) From 5 Minutes to 12 Hours Post-dose on Day 1 and From 22 to 24 Hours Post-dose on Day 2 | 1.46 Liters | Standard Error 0.009 |
| Placebo | Forced Expiratory Volume in 1 Second (FEV1) Standardized (With Respect to Time) Area Under the Curve (AUC) From 5 Minutes to 12 Hours Post-dose on Day 1 and From 22 to 24 Hours Post-dose on Day 2 | 1.32 Liters | Standard Error 0.009 |
Secondary
Peak Forced Expiratory Volume in 1 Second (FEV1) From 5 Minutes to 4 Hours Post-dose on Day 1
FEV1 was measured with spirometry conducted according to internationally accepted standards. Measurements were made in each treatment period at 5, 15, and 30 minutes and 1, 2, and 4 hours post-dose on Day 1. The analysis included baseline FEV1 prior to drug administration in the treatment period as a covariate.
Time frame: From 5 minutes to 4 hours post-dose on Day 1
Population: Modified intent-to-treat (modified ITT) population: All randomized patients who received at least 1 dose of study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Indacaterol 600 μg | Peak Forced Expiratory Volume in 1 Second (FEV1) From 5 Minutes to 4 Hours Post-dose on Day 1 | 1.58 Liters | Standard Error 0.009 |
| Indacaterol 300 µg | Peak Forced Expiratory Volume in 1 Second (FEV1) From 5 Minutes to 4 Hours Post-dose on Day 1 | 1.57 Liters | Standard Error 0.009 |
| Indacaterol 150 µg | Peak Forced Expiratory Volume in 1 Second (FEV1) From 5 Minutes to 4 Hours Post-dose on Day 1 | 1.54 Liters | Standard Error 0.009 |
| Placebo | Peak Forced Expiratory Volume in 1 Second (FEV1) From 5 Minutes to 4 Hours Post-dose on Day 1 | 1.42 Liters | Standard Error 0.009 |