Chronic Obstructive Pulmonary Disease
Conditions
Keywords
COPD, indacaterol, QAB149, inspiratory capacity
Brief summary
This study is being conducted to assess the effect of indacaterol (150 μg o.d.) on inspiratory capacity (IC), using placebo and open label tiotropium (18 μg o.d.) as comparators in patients with moderate chronic obstructive pulmonary disease (COPD). In particular, spirometric timepoints are included to elucidate the peak-IC in a period of approximately 4 hour post inhalation
Interventions
DRUGIndacaterol
Indacaterol 150µg once daily (o.d.) delivered via single-dose dry powder inhaler (SDDPI)
DRUGTiotropium
Tiotropium 18µg o.d. delivered via a proprietary inhalation device.
DRUGPlacebo
Placebo to indacaterol o.d. delivered via SDDPI
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
* Co-operative outpatients with a diagnosis of COPD (moderate as classified by the GOLD Guidelines, 2008) and including: * Smoking history of at least 10 pack years * Post-bronchodilator FEV1 \<80% and ≥50% of the predicted normal value (Visit 2). * Post-bronchodilator FEV1/forced vital capacity (FVC) \<70% (Visit 2).
Exclusion criteria
* Patients who received any corticosteroid (including inhaled) for 3 months prior to screening Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Peak Inspiratory Capacity (IC) After 21 Days of Treatment | 21 days | IC was measured with spirometry conducted according to internationally accepted standards. Peak IC was defined as the maximum IC of the mean over the 3 values which were measured each at 30min, 2 hour, 3 hour and 4 hour post dose by body plethysmography. Analysis of variance model was used with the factors: center, period, treatment, and patients within center. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Peak Residual Volume (RV) After 21 Days of Treatment | 21 days | Peak RV was measured with spirometry conducted according to internationally accepted standards. Peak RV was calculated as the Total Lung Capacity minus the maximum of the three Inspiratory Vital Capacity measurements which were measured each at 30 min, 2 hours, 3 hours and 4 hours post dose (at days 21, 55 and 89). Analysis of variance model was used with the factors: center, period, treatment, and patients within center. |
| Peak Total Lung Capacity (TLC) After 21 Days of Treatment | 21 days | TLC was measured with spirometry conducted according to internationally accepted standards. Peak TLC was calculated as the mean of the three Functional Residual Capacity peak measurements plus the mean of the three Inspiratory Capacity measurements which were measured each at 30 min, 2 hours, 3 hours and 4 hours post dose (at days 21, 55 and 89). Analysis of variance model was used with the factors: center, period, treatment, and patients within center. |
| Peak Residual Volume/Peak Total Lung Capacity (RV/TLC) Ratio After 21 Days of Treatment | 21 days | Peak RV/TLC ratio was measured with spirometry conducted according to internationally accepted standards. Peak RV/TLC was defined as the peak RV/peak TLC. Analysis of variance model was used with the factors: center, period, treatment, and patients within center. |
| Trough IC After 20 Days of Treatment | 20 days | Trough IC was measured with spirometry conducted according to internationally accepted standards. Trough IC was calculated as the mean of the three measurements of pre-dose body plethysmography (days 21, 55 and 89). Analysis of variance model was used with the factors: center, period, treatment, and patients within center. |
| FEV1 30 Minutes Post-dose After 21 Days of Treatment | 21 days | FEV1 was measured with spirometry conducted according to internationally accepted standards. FEV1 was measured 30 minutes post-dose. Analysis of variance model was used with the factors: center, period, treatment, and patients within center. |
| Trough Forced Expiratory Volume in 1 Second (FEV1) After 20 Days of Treatment | 20 days | FEV1 was measured with spirometry conducted according to internationally accepted standards. FEV1 was measured pre-dose after 20 days of treatment. Analysis of variance model was used with the factors: center, period, treatment, and patients within center. |
| Peak Specific Airway Resistance (sRaw) After 21 Days of Treatment | 21 days | Peak sRaw was measured with spirometry conducted according to internationally accepted standards. Peak sRaw was the mean of the three measurements which were measured each at 30 min, 2 hours, 3 hours and 4 hours post dose (at days 21, 55 and 89). Analysis of variance model was used with the factors: center, period, treatment, and patients within center. |
Countries
Germany
Participant flow
Pre-assignment details
173 participants were screened. 129 participants entered the study.
Participants by arm
| Arm | Count |
|---|---|
| Safety Set The safety set included all participants who received at least one dose of study medication during at least one study period. | 129 |
| Total | 129 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Treatment Period 1 | Administrative problems | 0 | 0 | 1 | 1 | 1 | 0 |
| Treatment Period 1 | Adverse Event | 1 | 0 | 1 | 0 | 0 | 0 |
| Treatment Period 1 | Protocol Violation | 0 | 0 | 0 | 2 | 1 | 0 |
| Treatment Period 1 | Unsatisfactory therapeutic effect | 0 | 0 | 0 | 0 | 1 | 0 |
| Treatment Period 1 | Withdrawal by Subject | 2 | 0 | 0 | 0 | 0 | 0 |
| Treatment Period 2 | Abnormal laboratory value(s) | 0 | 0 | 0 | 0 | 0 | 1 |
| Treatment Period 2 | Adverse Event | 0 | 1 | 1 | 0 | 0 | 0 |
| Treatment Period 2 | Unsatisfactory therapeutic effect | 0 | 1 | 1 | 0 | 0 | 0 |
| Treatment Period 2 | Withdrawal by Subject | 1 | 0 | 1 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Safety Set |
|---|---|
| Age, Continuous | 61.4 years STANDARD_DEVIATION 8.9 |
| Sex: Female, Male Female | 42 Participants |
| Sex: Female, Male Male | 87 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 | 20 / 118 | 16 / 120 | 10 / 119 |
| serious Total, serious adverse events | 1 / 118 | 1 / 120 | 3 / 119 |
Outcome results
Primary
Peak Inspiratory Capacity (IC) After 21 Days of Treatment
IC was measured with spirometry conducted according to internationally accepted standards. Peak IC was defined as the maximum IC of the mean over the 3 values which were measured each at 30min, 2 hour, 3 hour and 4 hour post dose by body plethysmography. Analysis of variance model was used with the factors: center, period, treatment, and patients within center.
Time frame: 21 days
Population: Full analysis set (FAS) included all randomized patients who received at least one dose of study medication during at least one study period. Participants with observations after 21 days were included in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Indacaterol | Peak Inspiratory Capacity (IC) After 21 Days of Treatment | 2.69 Liters |
| Placebo | Peak Inspiratory Capacity (IC) After 21 Days of Treatment | 2.48 Liters |
| Tiotropium | Peak Inspiratory Capacity (IC) After 21 Days of Treatment | 2.63 Liters |
Secondary
FEV1 30 Minutes Post-dose After 21 Days of Treatment
FEV1 was measured with spirometry conducted according to internationally accepted standards. FEV1 was measured 30 minutes post-dose. Analysis of variance model was used with the factors: center, period, treatment, and patients within center.
Time frame: 21 days
Population: Full analysis set (FAS) included all randomized patients who received at least one dose of study medication during at least one study period. Participants with observations after 21 days were included in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Indacaterol | FEV1 30 Minutes Post-dose After 21 Days of Treatment | 1.92 Liters |
| Placebo | FEV1 30 Minutes Post-dose After 21 Days of Treatment | 1.68 Liters |
| Tiotropium | FEV1 30 Minutes Post-dose After 21 Days of Treatment | 1.91 Liters |
Secondary
Peak Residual Volume/Peak Total Lung Capacity (RV/TLC) Ratio After 21 Days of Treatment
Peak RV/TLC ratio was measured with spirometry conducted according to internationally accepted standards. Peak RV/TLC was defined as the peak RV/peak TLC. Analysis of variance model was used with the factors: center, period, treatment, and patients within center.
Time frame: 21 days
Population: Modified intent-to-treat (mITT) excluded patients from centers who performed invalid body plethysmography. Participants with observations after 21 days were included in this analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Indacaterol | Peak Residual Volume/Peak Total Lung Capacity (RV/TLC) Ratio After 21 Days of Treatment | 0.52 Ratio |
| Placebo | Peak Residual Volume/Peak Total Lung Capacity (RV/TLC) Ratio After 21 Days of Treatment | 0.57 Ratio |
| Tiotropium | Peak Residual Volume/Peak Total Lung Capacity (RV/TLC) Ratio After 21 Days of Treatment | 0.53 Ratio |
Secondary
Peak Residual Volume (RV) After 21 Days of Treatment
Peak RV was measured with spirometry conducted according to internationally accepted standards. Peak RV was calculated as the Total Lung Capacity minus the maximum of the three Inspiratory Vital Capacity measurements which were measured each at 30 min, 2 hours, 3 hours and 4 hours post dose (at days 21, 55 and 89). Analysis of variance model was used with the factors: center, period, treatment, and patients within center.
Time frame: 21 days
Population: Modified intent-to-treat (mITT) excluded patients from centers who performed invalid body plethysmography. Participants with observations after 21 days were included in this analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Indacaterol | Peak Residual Volume (RV) After 21 Days of Treatment | 3.77 Liters |
| Placebo | Peak Residual Volume (RV) After 21 Days of Treatment | 4.17 Liters |
| Tiotropium | Peak Residual Volume (RV) After 21 Days of Treatment | 3.79 Liters |
Secondary
Peak Specific Airway Resistance (sRaw) After 21 Days of Treatment
Peak sRaw was measured with spirometry conducted according to internationally accepted standards. Peak sRaw was the mean of the three measurements which were measured each at 30 min, 2 hours, 3 hours and 4 hours post dose (at days 21, 55 and 89). Analysis of variance model was used with the factors: center, period, treatment, and patients within center.
Time frame: 21 days
Population: Full analysis set (FAS) included all randomized patients who received at least one dose of study medication during at least one study period. Participants with observations after 21 days were included in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Indacaterol | Peak Specific Airway Resistance (sRaw) After 21 Days of Treatment | 2.05 kPa*sec |
| Placebo | Peak Specific Airway Resistance (sRaw) After 21 Days of Treatment | 3.08 kPa*sec |
| Tiotropium | Peak Specific Airway Resistance (sRaw) After 21 Days of Treatment | 2.00 kPa*sec |
Secondary
Peak Total Lung Capacity (TLC) After 21 Days of Treatment
TLC was measured with spirometry conducted according to internationally accepted standards. Peak TLC was calculated as the mean of the three Functional Residual Capacity peak measurements plus the mean of the three Inspiratory Capacity measurements which were measured each at 30 min, 2 hours, 3 hours and 4 hours post dose (at days 21, 55 and 89). Analysis of variance model was used with the factors: center, period, treatment, and patients within center.
Time frame: 21 days
Population: Modified intent-to-treat (mITT) excluded patients from centers who performed invalid body plethysmography. Participants with observations after 21 days were included in this analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Indacaterol | Peak Total Lung Capacity (TLC) After 21 Days of Treatment | 7.25 Liters |
| Placebo | Peak Total Lung Capacity (TLC) After 21 Days of Treatment | 7.38 Liters |
| Tiotropium | Peak Total Lung Capacity (TLC) After 21 Days of Treatment | 7.25 Liters |
Secondary
Trough Forced Expiratory Volume in 1 Second (FEV1) After 20 Days of Treatment
FEV1 was measured with spirometry conducted according to internationally accepted standards. FEV1 was measured pre-dose after 20 days of treatment. Analysis of variance model was used with the factors: center, period, treatment, and patients within center.
Time frame: 20 days
Population: Full analysis set (FAS) included all randomized patients who received at least one dose of study medication during at least one study period. Participants with observations after 20 days were included in the analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Indacaterol | Trough Forced Expiratory Volume in 1 Second (FEV1) After 20 Days of Treatment | 1.80 Liters |
| Placebo | Trough Forced Expiratory Volume in 1 Second (FEV1) After 20 Days of Treatment | 1.61 Liters |
| Tiotropium | Trough Forced Expiratory Volume in 1 Second (FEV1) After 20 Days of Treatment | 1.78 Liters |
Secondary
Trough IC After 20 Days of Treatment
Trough IC was measured with spirometry conducted according to internationally accepted standards. Trough IC was calculated as the mean of the three measurements of pre-dose body plethysmography (days 21, 55 and 89). Analysis of variance model was used with the factors: center, period, treatment, and patients within center.
Time frame: 20 days
Population: Modified intent-to-treat (mITT) excluded patients from centers who performed invalid body plethysmography. Participants with observations after 20 days were included in this analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Indacaterol | Trough IC After 20 Days of Treatment | 2.43 Liters |
| Placebo | Trough IC After 20 Days of Treatment | 2.28 Liters |
| Tiotropium | Trough IC After 20 Days of Treatment | 2.39 Liters |