Official Title: “A Phase III, Randomized, Double-Blind, Triple-Dummy, Placebo Controlled, Multicenter, 5-Period, Single-Dose Complete Block Crossover Study to Determine the Onset of Action of Indacaterol (150 and 300 μg) in Patients With Moderate to Severe COPD Using Salbutamol (200 μg) and Salmeterol/Fluticasone (50/500 μg) as Active Controls”

This study will evaluate the onset of action of indacaterol (150 and 300 µg) as compared to salbutamol 200 µg and salmeterol/fluticasone 50/500 µg

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Investigator, Outcomes Assessor), Active Control, Crossover Assignment, Efficacy Study

Study Primary Completion Date: August 2008

Intervention(s) in this Clinical Trial

• Drug: Indacaterol 150 µg
• Drug: Indacaterol 300 µg
• Drug: Salmeterol/fluticasone (50/500 μg)
• Drug: Salbutamol 200 µg
• Drug: Placebo

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
  • Indacaterol 150 µg single dose, delivered via single-dose dry powder inhaler (SDDPI)
• Experimental: 2
  • Indacaterol 300 µg single dose, delivered via single-dose dry powder inhaler (SDDPI)
• Active Comparator: 3
  • Salmeterol/fluticasone (50/500 μg) fixed-dose combination delivered via manufacturer's proprietary multi-dose dry-powder inhaler (MDDPI)
• Active Comparator: 4
  • Salbutamol 200 μg delivered via manufacturer's proprietary multi-dose dry-powder inhaler (MDDPI)
• Placebo Comparator: 5
  • Placebo delivered via matching devices

Primary Measures

• Forced expiratory volume in 1 second (FEV1) at 5 mins post dose of indacaterol (150 and/or 300 μg) as compared to placebo

Secondary Measures

• FEV1 at 5 mins post dose of indacaterol (150 and 300 μg) versus salmeterol/fluticasone (50/500 μg)
• FEV1 at 5 mins post dose of indacaterol (150 and 300 μg) versus salbutamol (200 μg)
• FEV1 at 5 mins post dose of salmeterol/fluticasone (50/500 μg) and salbutamol (200 μg) versus placebo

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 COPD (moderate-to-severe as classified by the 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/FVC < 70%, where FVC is forced vital capacity ('Post-' refers to 15-30 mins 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 15h 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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 40 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Novartis

Information obtained from ClinicalTrials.gov on October 10, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00669617

Study ID Number: CQAB149B2307

ClinicalTrials.gov Identifier: NCT00669617

Health Authority: Germany: Federal Institute for Drugs and Medical Devices