Study to Determine the Onset of Action of Indacaterol in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD)

Novartis

Status and phase: Completed; Phase 3

Conditions: Chronic Obstructive Pulmonary Disease

Treatments: Drug: Indacaterol; Drug: Salmeterol/fluticasone (50/500 μg); Drug: Placebo to salbutamol; Drug: Salbutamol (200 µg); Drug: Placebo to Indacaterol; Drug: Placebo to Salmeterol/fluticasone

Study type: Interventional

Funder types: Industry

Identifiers

NCT00669617

CQAB149B2307

EUDRACT: 2007-006189-14

Details and patient eligibility

About

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

Enrollment: 89 patients

Sex: All

Ages: 40+ years old

Volunteers: No Healthy Volunteers

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• Concomitant pulmonary disease, pulmonary tuberculosis (unless chest x-ray confirms no longer active) or clinically significant bronchiectasis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/exclusion criteria may apply

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Triple Blind

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89 participants in 5 patient groups

Ind 150μg, Salm/flut, Ind 300μg, Placebo, Salbut

Experimental group

Description:

Participants received a single dose of each treatment from Period I - V in the following order, separated by a washout period of 4-7 days: Indacaterol 150 μg (Ind 150μg), Salmeterol/fluticasone 50/500 μg (Salm/flut), Indacaterol 300 μg (Ind 300μg), Placebo, Salbutamol 200 μg (Salbut). At each treatment visit, participants received the specified treatment and 2 placebo inhalations (one inhalation from the SDDPI, and one inhalation from each of the two MDDPIs) to maintain blinding. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.

Treatment:

Drug: Placebo to Indacaterol

Drug: Salmeterol/fluticasone (50/500 μg)

Drug: Placebo to salbutamol

Drug: Placebo to Salmeterol/fluticasone

Drug: Salbutamol (200 µg)

Drug: Indacaterol

Ind 300μg, Ind 150μg, Salbut, Salm/flut, Placebo

Experimental group

Description:

Participants received a single dose of each treatment from Period I - V in the following order, separated by a washout period of 4-7 days: Indacaterol 300 μg (Ind 300μg), Indacaterol 150 μg (Ind 150μg), Salbutamol 200 μg (Salbut), Salmeterol/fluticasone 50/500 μg (Salm/flut), Placebo. At each treatment visit, participants received the specified treatment and 2 placebo inhalations (one inhalation from the SDDPI, and one inhalation from each of the two MDDPIs) to maintain blinding. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.

Treatment:

Drug: Placebo to Indacaterol

Drug: Salmeterol/fluticasone (50/500 μg)

Drug: Placebo to salbutamol

Drug: Placebo to Salmeterol/fluticasone

Drug: Salbutamol (200 µg)

Drug: Indacaterol

Salm/flut, Placebo, Ind 150μg, Salbut, Ind 300μg

Experimental group

Description:

Participants received a single dose of each treatment from Period I - V in the following order, separated by a washout period of 4-7 days: Salmeterol/fluticasone 50/500 μg (Salm/flut), Placebo, Indacaterol 150 μg (Ind 150μg), Salbutamol 200 μg (Salbut), Indacaterol 300 μg (Ind 300μg). At each treatment visit, participants received the specified treatment and 2 placebo inhalations (one inhalation from the SDDPI, and one inhalation from each of the two MDDPIs) to maintain blinding. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.

Treatment:

Drug: Placebo to Indacaterol

Drug: Salmeterol/fluticasone (50/500 μg)

Drug: Placebo to salbutamol

Drug: Placebo to Salmeterol/fluticasone

Drug: Salbutamol (200 µg)

Drug: Indacaterol

Salbut, Ind 300μg, Placebo, Ind 150μg, Salm/flut

Experimental group

Description:

Participants received a single dose of each treatment from Period I - V in the following order, separated by a washout period of 4-7 days: Salbutamol 200 μg (Salbut), Indacaterol 300 μg (Ind 300μg), Placebo, Indacaterol 150 μg (Ind 150μg), Salmeterol/fluticasone 50/500 μg (Salm/flut). At each treatment visit, participants received the specified treatment and 2 placebo inhalations (one inhalation from the SDDPI, and one inhalation from each of the two MDDPIs) to maintain blinding. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.

Treatment:

Drug: Placebo to Indacaterol

Drug: Salmeterol/fluticasone (50/500 μg)

Drug: Placebo to salbutamol

Drug: Placebo to Salmeterol/fluticasone

Drug: Salbutamol (200 µg)

Drug: Indacaterol

Placebo, Salbut, Salm/flut , Ind 300μg, Ind 150μg

Experimental group

Description:

Participants received a single dose of each treatment from Period I - V in the following order, separated by a washout period of 4-7 days: Placebo, Salbutamol 200 μg (Salbut), Salmeterol/fluticasone 50/500 μg (Salm/flut), Indacaterol 300 μg (Ind 300μg), Indacaterol 150 μg (Ind 150μg). At each treatment visit, participants received the specified treatment and 2 placebo inhalations (one inhalation from the SDDPI, and one inhalation from each of the two MDDPIs) to maintain blinding. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.

Treatment:

Drug: Placebo to Indacaterol

Drug: Salmeterol/fluticasone (50/500 μg)

Drug: Placebo to salbutamol

Drug: Placebo to Salmeterol/fluticasone

Drug: Salbutamol (200 µg)

Drug: Indacaterol