Chronic Obstructive Pulmonary Disease (COPD)
Conditions
Keywords
Chronic obstructive pulmonary disease, indacaterol, tiotropium, placebo controlled
Brief summary
The study compared the 24-hour spirometry profile of indacaterol with that of placebo and with tiotropium as an active control in patients with chronic obstructive pulmonary disease.
Interventions
DRUGIndacaterol
Indacaterol 150 μg or 300 μg, delivered via SDDPI
DRUGTiotropium
Tiotropium 18 μg once daily delivered via inhalation device
DRUGPlacebo
Placebo to indacaterol (150 or 300 μg) delivered via SDDPI. The placebo for blinding tiotropium was delivered via the tiotropium manufacturer's proprietary inhalation device (HandiHaler®)
Sponsors
Novartis
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
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 out patients 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: 1. Smoking history of at least 10 pack years (current or previous smokers) 2. Post-bronchodilator forced expiratory volume in 1 second (FEV1) \< 80% and ≥30% of the predicted normal value. 3. Post-bronchodilator FEV1/Forced vital capacity (FVC) \< 70%
Exclusion criteria
* 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 for chronic hypoxemia * Patients who have had a respiratory tract infection within 6 weeks prior to Visit * 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 * Any patient with active cancer or a history of cancer with less than 5 years disease free survival time * Patients with a history of long QT syndrome or whose QTc interval (Bazett's) measured at Visit 1 or randomization is prolonged * Patients who have been vaccinated with live attenuated vaccines within 30 days prior to screening or during the run-in period. * Patients unable to successfully use a dry powder inhaler device, MDI or perform spirometry measurements Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 24-hour Post-dose Trough Forced Expiratory Volume in 1 Second (FEV1) After 14 Days of Treatment | 23 hours 10 minutes and 23 hours 45 minutes post-dose on Day 15 of each treatment period | FEV1 was measured with spirometry conducted according to internationally accepted standards. Trough FEV1 was defined as the mean of FEV1 measurements at 23 h 10 min and 23 h 45 min post Day 14 dose measured on the morning of Day 15 in each treatment period. The model used for analysis contained 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 |
|---|---|---|
| Peak FEV1 During 4 Hours Post Morning Dose on Day 1 | Day 1 (from 0 to 4 hours post morning dose) | FEV1 was measured with spirometry conducted according to internationally accepted standards. The peak effect on Day 1 was defined as the maximum FEV1 during the first 4 hour on that day. FEV1 measurements taken within 6 hour of rescue use were set to missing before the peak FEV1 (0-4 hour) was calculated. The model used for analysis contained 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
Australia, Germany, Netherlands, New Zealand, Poland, South Africa, Spain
Participant flow
Recruitment details
Patients were randomized to one of the 4 possible treatment sequences of the double-blind 10-week treatment phase (Week 1 - 10) to receive three out of the four study treatments. Each treatment sequence was divided into three 2-week treatment periods (I/II/III), with periods I and II followed by 2-week washout periods.
Pre-assignment details
Out of total 169 randomized patients, two patients were discontinued before exposure to any treatment in period I because of administrative problems.
Participants by arm
| Arm | Count |
|---|---|
| Total Patients The safety population, included all patients who received at least one dose of study drug. | 167 |
| Total | 167 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Period I | Abnormal test procedure results | 1 | 1 | 1 | 0 |
| Period I | Adverse Event | 2 | 0 | 1 | 0 |
| Period I | Subject withdrew consent | 1 | 0 | 0 | 1 |
| Period II | Adverse Event | 1 | 0 | 0 | 0 |
| Period II | Lost to Follow-up | 0 | 0 | 0 | 1 |
| Period III | Administrative problems | 0 | 1 | 1 | 0 |
| Period III | Adverse Event | 0 | 1 | 0 | 0 |
| Period III | Unsatisfactory therapeutic effect | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Total Patients |
|---|---|
| Age Continuous | 64.5 years STANDARD_DEVIATION 7.92 |
| Sex: Female, Male Female | 39 Participants |
| Sex: Female, Male Male | 128 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 | 15 / 118 | 17 / 122 | 11 / 120 | 13 / 123 |
| serious Total, serious adverse events | 2 / 118 | 1 / 122 | 4 / 120 | 1 / 123 |
Outcome results
Primary
24-hour Post-dose Trough Forced Expiratory Volume in 1 Second (FEV1) After 14 Days of Treatment
FEV1 was measured with spirometry conducted according to internationally accepted standards. Trough FEV1 was defined as the mean of FEV1 measurements at 23 h 10 min and 23 h 45 min post Day 14 dose measured on the morning of Day 15 in each treatment period. The model used for analysis contained 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: 23 hours 10 minutes and 23 hours 45 minutes post-dose on Day 15 of each treatment period
Population: The modified intent-to-treat (mITT) population, included all randomized patients who received at least one dose of study drug. Patients were analyzed according to treatment they received.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Indacaterol 150 μg | 24-hour Post-dose Trough Forced Expiratory Volume in 1 Second (FEV1) After 14 Days of Treatment | 1.53 Liters | Standard Error 0.021 |
| Indacaterol 300 μg | 24-hour Post-dose Trough Forced Expiratory Volume in 1 Second (FEV1) After 14 Days of Treatment | 1.51 Liters | Standard Error 0.021 |
| Tiotropium 18 μg | 24-hour Post-dose Trough Forced Expiratory Volume in 1 Second (FEV1) After 14 Days of Treatment | 1.48 Liters | Standard Error 0.021 |
| Placebo | 24-hour Post-dose Trough Forced Expiratory Volume in 1 Second (FEV1) After 14 Days of Treatment | 1.36 Liters | Standard Error 0.021 |
Secondary
Peak FEV1 During 4 Hours Post Morning Dose on Day 1
FEV1 was measured with spirometry conducted according to internationally accepted standards. The peak effect on Day 1 was defined as the maximum FEV1 during the first 4 hour on that day. FEV1 measurements taken within 6 hour of rescue use were set to missing before the peak FEV1 (0-4 hour) was calculated. The model used for analysis contained 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: Day 1 (from 0 to 4 hours post morning dose)
Population: The modified intent-to-treat (mITT) population, included all randomized patients who received at least one dose of study drug.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Indacaterol 150 μg | Peak FEV1 During 4 Hours Post Morning Dose on Day 1 | 1.65 Liters | Standard Error 0.015 |
| Indacaterol 300 μg | Peak FEV1 During 4 Hours Post Morning Dose on Day 1 | 1.67 Liters | Standard Error 0.015 |
| Tiotropium 18 μg | Peak FEV1 During 4 Hours Post Morning Dose on Day 1 | 1.62 Liters | Standard Error 0.015 |
| Placebo | Peak FEV1 During 4 Hours Post Morning Dose on Day 1 | 1.48 Liters | Standard Error 0.015 |