Chronic Obstructive Pulmonary Disease (COPD)
Conditions
Keywords
COPD, bronchodilator, long acting beta agonist, LABA
Brief summary
This study was conducted to provide detailed information on the efficacy of indacaterol (in terms of the spirometry assessment forced expiratory volume in 1 second \[FEV1\]) over the full 24-h time period
Interventions
DRUGIndacaterol
300 µg dosed in the morning/evening via single dose dry powder inhaler (SDDPI)
DRUGSalmeterol
50 µg twice daily delivered via dry powder inhaler (DPI)
DRUGPlacebo to Indacaterol
Placebo matching indacaterol was delivered via SDDPI.
Placebo matching salmeterol was delivered via DPI
Sponsors
Novartis
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male and female adults aged ≥ 40 years, who have signed an Informed Consent Form prior to initiation of any study-related procedure * Co-operative outpatients with a diagnosis of chronic obstructive pulmonary disease (COPD) (moderate to severe as classified by the Global initiative for chronic obstructive lung disease (GOLD) Guidelines, 2006) and: * Smoking history of at least 20 pack years * Post-bronchodilator FEV1 \< 80% and ≥30% of the predicted normal value * Post-bronchodilator FEV1/forced vital capacity (FVC) \< 70%
Exclusion criteria
* Pregnant or lactating females * Patients who have been hospitalized for a COPD exacerbation in the 6 weeks prior to Visit 1 or during the run-in period * Patients requiring long term oxygen therapy (\>15 h a day) * Patient who have had a respiratory tract infection 6 weeks prior to V2 (with further criteria) * Patients with concomitant pulmonary disease, pulmonary tuberculosis, or clinically significant bronchiectasis * Patients with history of asthma (with further criteria) * Patients with Type I or uncontrolled type II diabetes. * Patients who have clinically relevant laboratory abnormalities or a clinically significant abnormality * Any patient with active cancer or a history of cancer with less than 5 years disease free survival time * Patient with a history with long QT syndrome or whose QTc interval is prolonged * Patients with a hypersensitivity to any of the study drugs or drugs with similar chemical structure * Patients who have had treatment with an investigational drug (with further criteria) * Patients who have had live attenuated vaccination within 30 days prior to Visit 2, or during run-in period * Patients with known history of non compliance to medication * Patients unable to satisfactorily 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) Following 14 Days of Evening Dosing of Indacaterol Versus Placebo | After 14 days of treatment | Trough FEV1 was assessed by performing spirometry measurements in the clinic for each treatment period. For the primary efficacy variable, trough FEV1 is the mean of two measurements taken at 23h 10 min and 23h 45 min post dose. The primary variable was analyzed using an analysis of covariance (ANCOVA) model with the (period) baseline FEV1 as covariate. The (period) baseline FEV1 was defined as the value measured before the study drug administration in that treatment period. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Trough FEV1 Assessed After 14 Days of Dosing for All Other Treatment Comparisons | After 14 days of dosing | Trough FEV1 was assessed by performing spirometry measurements in the clinic for each treatment period. On the morning and evening of Day 15 trough FEV1 (i.e. mean of measurements performed 23 h 10 min and 23 h 45 min post-dose) were assessed. An analysis of covariance (ANCOVA) model was used with the (period) baseline FEV1 as covariate. The (period) baseline FEV1 was defined as the value measured before the study drug administration in that treatment period. |
Countries
France, Germany, Spain
Participant flow
Recruitment details
Patients were randomized to one of the 12 possible treatment sequences of the double-blind 10-week treatment phase (Week 1 - 10). Each treatment sequence was divided into three treatment periods (I/II/III) of 15-day duration each. The first and second treatment period of each sequence was followed by a 2-week washout period.
Pre-assignment details
Total 96 patients were randomized; one randomized patient discontinued from the study prior to exposure to study drug because of abnormal test procedure(s) result.
Participants by arm
| Arm | Count |
|---|---|
| Total Patients | 95 |
| Total | 95 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Period I | Abnormal laboratory value(s) | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Period I | Administrative problem | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Period I | Protocol deviation | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Period I | Subject withdrew consent | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 1 |
| Period II | Adverse Event | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Period II | Subject withdrew consent | 0 | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Period III | Administrative problems | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Total Patients |
|---|---|
| Age Continuous | 64.1 years STANDARD_DEVIATION 8.7 |
| Sex: Female, Male Female | 15 Participants |
| Sex: Female, Male Male | 80 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 | 10 / 65 | 4 / 68 | 3 / 68 | 5 / 68 |
| serious Total, serious adverse events | 0 / 65 | 1 / 68 | 0 / 68 | 0 / 68 |
Outcome results
Primary
Trough Forced Expiratory Volume in 1 Second (FEV1) Following 14 Days of Evening Dosing of Indacaterol Versus Placebo
Trough FEV1 was assessed by performing spirometry measurements in the clinic for each treatment period. For the primary efficacy variable, trough FEV1 is the mean of two measurements taken at 23h 10 min and 23h 45 min post dose. The primary variable was analyzed using an analysis of covariance (ANCOVA) model with the (period) baseline FEV1 as covariate. The (period) baseline FEV1 was defined as the value measured before the study drug administration in that treatment period.
Time frame: After 14 days of treatment
Population: The modified intention-to-treat (mITT) population included all randomized patients who received at least one dose of study drug. Patients who received only one treatment were also included for calculation of treatment means. This analysis included all patients who received indacaterol in the evening or placebo in their assigned treatment sequence.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Indacaterol Evening | Trough Forced Expiratory Volume in 1 Second (FEV1) Following 14 Days of Evening Dosing of Indacaterol Versus Placebo | 1.57 Liters | Standard Error 0.025 |
| Placebo | Trough Forced Expiratory Volume in 1 Second (FEV1) Following 14 Days of Evening Dosing of Indacaterol Versus Placebo | 1.37 Liters | Standard Error 0.025 |
Secondary
Trough FEV1 Assessed After 14 Days of Dosing for All Other Treatment Comparisons
Trough FEV1 was assessed by performing spirometry measurements in the clinic for each treatment period. On the morning and evening of Day 15 trough FEV1 (i.e. mean of measurements performed 23 h 10 min and 23 h 45 min post-dose) were assessed. An analysis of covariance (ANCOVA) model was used with the (period) baseline FEV1 as covariate. The (period) baseline FEV1 was defined as the value measured before the study drug administration in that treatment period.
Time frame: After 14 days of dosing
Population: The modified intention-to-treat (mITT) population included all randomized patients who received at least one dose of study drug. Patients who received only one treatment were also included for calculation of treatment means.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Indacaterol Evening | Trough FEV1 Assessed After 14 Days of Dosing for All Other Treatment Comparisons | 1.56 Liters | Standard Error 0.025 |
| Placebo | Trough FEV1 Assessed After 14 Days of Dosing for All Other Treatment Comparisons | 1.57 Liters | Standard Error 0.025 |
| Salmeterol Morning | Trough FEV1 Assessed After 14 Days of Dosing for All Other Treatment Comparisons | 1.51 Liters | Standard Error 0.025 |
| Salmeterol Evening | Trough FEV1 Assessed After 14 Days of Dosing for All Other Treatment Comparisons | 1.46 Liters | Standard Error 0.025 |
| Placebo Morning | Trough FEV1 Assessed After 14 Days of Dosing for All Other Treatment Comparisons | 1.36 Liters | Standard Error 0.025 |
| Placebo Evening | Trough FEV1 Assessed After 14 Days of Dosing for All Other Treatment Comparisons | 1.37 Liters | Standard Error 0.025 |