Chronic Obstructive Pulmonary Disease
Conditions
Keywords
chronic obstructive pulmonary disease, COPD, indacaterol, adults
Brief summary
This study will evaluate the onset of action of indacaterol (150 and 300 µg) as compared to placebo, salbutamol 200 µg and salmeterol/fluticasone 50/500 µg
Interventions
DRUGIndacaterol
Indacaterol 150 and 300 μg, delivered via single-dose dry-powder inhaler (SDDPI)
DRUGSalmeterol/fluticasone (50/500 μg)
Salmeterol/fluticasone 50/500 μg fixed-dose combination delivered via manufacturer's proprietary Multi-Dose Dry-Powder Inhaler (MDDPI).
DRUGSalbutamol (200 µg)
Salbutamol 200 μg delivered via manufacturer's proprietary Multi-Dose Dry-Powder Inhaler (MDDPI).
DRUGPlacebo to Indacaterol
Placebo to indacaterol delivered via SDDPI
DRUGPlacebo to Salmeterol/fluticasone
Placebo to salmeterol/fluticasone delivered via MDDPI
DRUGPlacebo to salbutamol
Placebo to salbutamol delivered via MDDPI
Sponsors
Novartis
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
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 * Patients with a diagnosis of Chronic Obstructive Pulmonary Disease (COPD) (moderate-to-severe as classified by the GOLD Guidelines, 2006) and: * Smoking history of at least 20 pack years * Post-bronchodilator Forced Expiratory Volume in 1 Second (FEV1) \<80% and ≥30% of the predicted normal value. * Post-bronchodilator FEV1/Forced Vital Capacity (FVC) \< 70%, where FVC is forced vital capacity ('Post-' refers to 15-30 minutes after inhalation of 400 μg of salbutamol at Visit 2)
Exclusion criteria
* Pregnant / nursing women or women of child-bearing potential * Long term oxygen therapy (more than 15 hours per day) on a daily basis for chronic hypoxemia * Patients hospitalized for COPD exacerbation in 6 weeks prior to Visit 2 and up to Visit 3 * Respiratory tract infection within 6 weeks prior to Visit 2 and up to Visit 3 * Concomitant pulmonary disease, pulmonary tuberculosis (unless chest x-ray confirms no longer active) or clinically significant bronchiectasis * Any history of asthma, including: blood eosinophil count \>400/mm3; onset of asthma symptoms prior to age 40 years * History of long QT syndrome or whose QTc (Bazett's) measured at Visit 2 or Visit 3 is prolonged (\>450ms for males or \>470ms for females) * Clinically relevant lab abnormalities / conditions such as (but not limited to) unstable ischemic heart disease, arrhythmia (excluding stable AF), uncontrolled hypertension, uncontrolled hypo- and hyperthyroidism, hypokalemia, hyperadrenergic state or any condition which in the investigator's opinion might compromise patient safety or compliance, interfere with evaluation, or preclude completion of the study * Uncontrolled Type I / Type II Diabetes or blood glucose outside normal or HbA1c \>8.0% of total hemoglobin measured at Visit 2 * Any patient with lung cancer or any active cancer or a history of cancer with less than 5 years disease-free survival time * History of hypersensitivity to any of the study drugs * Irregular day/night, waking/sleeping cycles e.g. shift workers * Live attenuated vaccinations within 30 days prior to Visit 2 * Investigational drug within 30 days prior to Visit 2 * Known history of non-compliance or not able to use devices or perform spirometry Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Forced Expiratory Volume in 1 Second (FEV1) at 5 Minutes Post-dose | Five Minutes Post Dose | FEV1 was measured at 5 minutes after dosing with spirometry conducted according to internationally accepted standards. The time of dosing was defined as the time corresponding to the use of the first inhaler device. The primary variable was analyzed using a mixed model containing the period baseline FEV1 as covariate. The period baseline FEV1 was the average of the FEV1 value measured in the clinic at 50 and 15 min prior to the study drug administration in that period. |
Countries
Belgium, Germany, Hungary, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Total Population Participants were randomized to one of five treatment sequences. Each treatment sequence comprised 5 double-blind, single dose treatment periods (Periods I to V), separated by a washout period of 4-7 days. Participants received each of the 5 blinded-treatments: indacaterol 150 μg, indacaterol 300 μg, salmeterol/fluticasone 50/500 μg, salbutamol 200 μg and placebo. | 89 |
| Total | 89 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Period 1 | Protocol Deviation | 0 | 0 | 0 | 0 | 1 |
| Period 1 | Withdrawal by Subject | 0 | 0 | 1 | 0 | 0 |
| Period 3 | Lost to Follow-up | 1 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Total Population |
|---|---|
| Age Continuous | 62.3 years STANDARD_DEVIATION 8.37 |
| Sex: Female, Male Female | 35 Participants |
| Sex: Female, Male Male | 54 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 86 | 0 / 87 | 0 / 86 | 0 / 88 | 0 / 87 |
| serious Total, serious adverse events | 0 / 86 | 0 / 87 | 0 / 86 | 0 / 88 | 0 / 87 |
Outcome results
Primary
Forced Expiratory Volume in 1 Second (FEV1) at 5 Minutes Post-dose
FEV1 was measured at 5 minutes after dosing with spirometry conducted according to internationally accepted standards. The time of dosing was defined as the time corresponding to the use of the first inhaler device. The primary variable was analyzed using a mixed model containing the period baseline FEV1 as covariate. The period baseline FEV1 was the average of the FEV1 value measured in the clinic at 50 and 15 min prior to the study drug administration in that period.
Time frame: Five Minutes Post Dose
Population: Modified Intent-to-Treat (mITT) population: including all randomized patients who received at least one dose of study drug. If any of the values used in the period baseline FEV1 and FEV1 at 5 min post-dose were collected within 6 hours of rescue medication, then the individual FEV1 value was set to missing.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Indacaterol 150 µg | Forced Expiratory Volume in 1 Second (FEV1) at 5 Minutes Post-dose | 1.48 Liters | Standard Error 0.014 |
| Indacaterol 300 µg | Forced Expiratory Volume in 1 Second (FEV1) at 5 Minutes Post-dose | 1.50 Liters | Standard Error 0.014 |
| Placebo | Forced Expiratory Volume in 1 Second (FEV1) at 5 Minutes Post-dose | 1.38 Liters | Standard Error 0.014 |
| Salmeterol/Fluticasone | Forced Expiratory Volume in 1 Second (FEV1) at 5 Minutes Post-dose | 1.43 Liters | Standard Error 0.014 |
| Salbutamol | Forced Expiratory Volume in 1 Second (FEV1) at 5 Minutes Post-dose | 1.47 Liters | Standard Error 0.014 |