A Crossover Study to Determine the Effect on Lung Function of Indacaterol in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD), Using Tiotropium as an Active Control

Study Overview
=================
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.

Official Title
-----------------
A Phase III, Randomized, Double-blind, Double-dummy, Placebo-controlled, Multicenter, 3-period Incomplete Block, Multidose Crossover Study to Determine the Effect on Lung Function of Indacaterol (150 and 300 μg o.d.) in Patients With Moderate to Severe COPD, Using Tiotropium (18 μg o.d.) as an Active Control

Conditions
-----------------
Chronic Obstructive Pulmonary Disease (COPD)

Intervention / Treatment
-----------------
* Drug: Indacaterol
* Drug: Tiotropium
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
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: Smoking history of at least 10 pack years (current or previous smokers) 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% 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/exclusion criteria may apply.

Ages Eligible for Study
-----------------
Minimum Age: 40 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sequence 1: Placebo,Tiotropium, Indacaterol 150 μg<br>In period I, placebo to indacaterol (150 or 300 μg) delivered via SDDPI. The placebo for blinding tiotropium was delivered via the tiotropium inhalation device. In period II, tiotropium (18 μg) once daily delivered via inhalation device and matching placebo to indacaterol delivered once daily via single dose dry powder inhaler (SDDPI). In period III, indacaterol 150 μg once daily delivered via SDDPI and placebo to tiotropium was delivered once daily via the tiotropium inhalation device. Daily inhaled corticosteroid (ICS) monotherapy (where applicable) was provided to remain stable throughout study. The Short acting (beta) β2-agonist (SABA) was available for rescue use throughout the study. | Drug: Indacaterol<br>* Indacaterol 150 μg or 300 μg, delivered via SDDPI<br>Drug: Tiotropium<br>* Tiotropium 18 μg once daily delivered via inhalation device<br>Drug: Placebo<br>* 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®)<br>|
| Experimental: Sequence 2: Indacaterol 300 μg, Indacaterol 150 μg, Tiotropium<br>In period I,indacaterol 300 μg once daily delivered via single dose dry powder inhaler (SDDPI)and matching placebo to tiotropium delivered once daily via tiotropium inhalation device. In period II, indacaterol 150 μg once daily delivered via SDDPI and matching placebo to tiotropium delivered once daily via tiotropium inhalation device. In period III, tiotropium (18 μg) once daily delivered via inhalation device and matching placebo to indacaterol delivered once daily via SDDPI. Daily ICS monotherapy (where applicable) was provided to remain stable throughout study. The SABA was available for rescue use throughout the study. | Drug: Indacaterol<br>* Indacaterol 150 μg or 300 μg, delivered via SDDPI<br>Drug: Tiotropium<br>* Tiotropium 18 μg once daily delivered via inhalation device<br>|
| Experimental: Sequence 3: Indacaterol 150 μg, Indacaterol 300 μg, Placebo<br>In period I, indacaterol 150 μg once daily delivered via SDDPI and matching placebo to tiotropium delivered once daily via tiotropium inhalation device. In period II, indacaterol 300 μg once daily delivered via SDDPI and matching placebo to tiotropium delivered once daily via tiotropium inhalation device. In period III, placebo to indacaterol (150 or 300 μg) delivered via SDDPI. The placebo for blinding tiotropium was delivered via the tiotropium inhalation device. Daily ICS monotherapy (where applicable) was provided to remain stable throughout study. The SABA was available for rescue use throughout the study. | Drug: Indacaterol<br>* Indacaterol 150 μg or 300 μg, delivered via SDDPI<br>Drug: Placebo<br>* 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®)<br>|
| Experimental: Sequence 4: Tiotropium, Placebo, Indacaterol 300 μg<br>In period I, tiotropium (18 μg) once daily delivered via inhalation device and matching placebo to indacaterol delivered once daily via SDDPI. In period II, placebo to indacaterol (150 or 300 μg) delivered via SDDPI. The placebo for blinding tiotropium was delivered via the tiotropium inhalation device. In period III, indacaterol 300 μg once daily delivered via SDDPI and matching placebo to tiotropium delivered once daily via tiotropium inhalation device. Daily ICS monotherapy (where applicable) was provided to remain stable throughout study. The SABA was available for rescue use throughout the study. | Drug: Indacaterol<br>* Indacaterol 150 μg or 300 μg, delivered via SDDPI<br>Drug: Tiotropium<br>* Tiotropium 18 μg once daily delivered via inhalation device<br>Drug: Placebo<br>* 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®)<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 23 hours 10 minutes and 23 hours 45 minutes post-dose on Day 15 of each treatment period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Day 1 (from 0 to 4 hours post morning dose) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Chronic obstructive pulmonary disease, indacaterol, tiotropium, placebo controlled