Dose Ranging Study of Indacaterol in Japanese Patients With Chronic Obstructive Pulmonary Disease (COPD)

Study Overview
=================
Brief Summary
-----------------
The study was designed to obtain data about the efficacy and safety of 3 doses of indacaterol (150, 300, and 600 µg) in Japanese patients with chronic obstructive pulmonary disease (COPD) so that optimal dose(s) could be chosen for testing in later studies.

Official Title
-----------------
A Randomized, Double-blind, Placebo-controlled, 4-period 4-treatment Crossover, Multicenter, Dose-ranging Study to Assess the Efficacy and Safety of 3 Doses of Indacaterol (150, 300, and 600 µg) Delivered Via a Single Dose Dry Powder Inhaler in Japanese Patients With Chronic Obstructive Pulmonary Disease (COPD)

Conditions
-----------------
Chronic Obstructive Pulmonary Disease

Intervention / Treatment
-----------------
* Drug: Indacaterol 150 μg
* Drug: Indacaterol 300 μg
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male and female Japanese aged 40 to 75 years old Moderate to severe chronic obstructive pulmonary disease (COPD) with smoking history of at least 20 pack years Exclusion Criteria: History of hospitalization for COPD exacerbation within past 6 months Use of long-term oxygen therapy History of asthma Respiratory tract infection within past 1 month Consistently very high or low blood sugar Clinically abnormal laboratory values or significant condition History of heart failure or heart attack within past 6 months History of long QT syndrome or long QT interval in electrocardiogram recorded at screening Other protocol-defined inclusion/exclusion criteria applied to the study.

Ages Eligible for Study
-----------------
Minimum Age: 40 Years
Maximum Age: 75 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: Placebo-indacaterol 150μg-indacaterol 300μg-indacaterol 600μg<br>In treatment period, 1 patients received 2 placebo capsules; in treatment period 2, patients received 1 indacaterol 150 μg capsule + 1 placebo capsule; in treatment period 3, patients received 1 indacaterol 300 μg capsule + 1 placebo capsule; and in treatment period 4, patients received 2 indacaterol 300 μg capsules. There was a washout period of 14-28 days between each treatment period. Patients received each treatment only once. The short-acting β2-agonist salbutamol was available for rescue use throughout the study. | Drug: Indacaterol 150 μg<br>* Indacaterol 150 μg was provided in powder filled capsules with a single dose dry powder inhaler (SDDPI).<br>Drug: Indacaterol 300 μg<br>* Indacaterol 300 μg was provided in powder filled capsules with a single dose dry powder inhaler (SDDPI).<br>Drug: Placebo<br>* Placebo to indacaterol was provided in powder filled capsules with a single dose dry powder inhaler (SDDPI).<br>|
| Experimental: Indacaterol 150μg-indacaterol 600μg-placebo-indacaterol 300μg<br>In treatment period 1, patients received 1 indacaterol 150 μg capsule + 1 placebo capsule; in treatment period 2, patients received 2 indacaterol 300 μg capsules; in treatment period 3, patients received 2 placebo capsules; and in treatment period 4, patients received 1 indacaterol 300 μg capsule + 1 placebo capsule. There was a washout period of 14-28 days between each treatment period. Patients received each treatment only once. The short-acting β2-agonist salbutamol was available for rescue use throughout the study. | Drug: Indacaterol 150 μg<br>* Indacaterol 150 μg was provided in powder filled capsules with a single dose dry powder inhaler (SDDPI).<br>Drug: Indacaterol 300 μg<br>* Indacaterol 300 μg was provided in powder filled capsules with a single dose dry powder inhaler (SDDPI).<br>Drug: Placebo<br>* Placebo to indacaterol was provided in powder filled capsules with a single dose dry powder inhaler (SDDPI).<br>|
| Experimental: Indacaterol 300μg-placebo-indacaterol 600μg-indacaterol 150μg<br>In treatment period 1, patients received 1 indacaterol 300 μg capsule + 1 placebo capsule; in treatment period 2, patients received 2 placebo capsules; in treatment period 3, patients received 2 indacaterol 300 μg capsules; and in treatment period 4, patients received 1 indacaterol 150 μg capsule + 1 placebo capsule. There was a washout period of 14-28 days between each treatment period. Patients received each treatment only once. The short-acting β2-agonist salbutamol was available for rescue use throughout the study. | Drug: Indacaterol 150 μg<br>* Indacaterol 150 μg was provided in powder filled capsules with a single dose dry powder inhaler (SDDPI).<br>Drug: Indacaterol 300 μg<br>* Indacaterol 300 μg was provided in powder filled capsules with a single dose dry powder inhaler (SDDPI).<br>Drug: Placebo<br>* Placebo to indacaterol was provided in powder filled capsules with a single dose dry powder inhaler (SDDPI).<br>|
| Experimental: Indacaterol 600μg-indacaterol 300μg-indacaterol 150μg-placebo<br>In treatment period 1, patients received 2 indacaterol 300 μg capsules; in treatment period 2, patients received 1 indacaterol 300 μg capsule + 1 placebo capsule; in treatment period 3, patients received 1 indacaterol 150 μg capsule + 1 placebo capsule; and in treatment period 4 patients received 2 placebo capsules. There was a washout period of 14-28 days between each treatment period. Patients received each treatment only once. The short-acting β2-agonist salbutamol was available for rescue use throughout the study. | Drug: Indacaterol 150 μg<br>* Indacaterol 150 μg was provided in powder filled capsules with a single dose dry powder inhaler (SDDPI).<br>Drug: Indacaterol 300 μg<br>* Indacaterol 300 μg was provided in powder filled capsules with a single dose dry powder inhaler (SDDPI).<br>Drug: Placebo<br>* Placebo to indacaterol was provided in powder filled capsules with a single dose dry powder inhaler (SDDPI).<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Forced Expiratory Volume in 1 Second (FEV1) Standardized (With Respect to Time) Area Under the Curve (AUC) From 22 to 24 Hours Post-dose on Day 2 | FEV1 was measured with spirometry conducted according to internationally accepted standards. Measurements were made in each treatment period at 22, 23, and 24 hours post-dose on Day 2. Standardized FEV1 AUC was calculated by the trapezoidal rule. The analysis included patient, period, and treatment group as fixed effects and baseline FEV1 prior to drug administration in the treatment period as a covariate. | From 22 to 24 hours post-dose on Day 2 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak Forced Expiratory Volume in 1 Second (FEV1) From 5 Minutes to 4 Hours Post-dose on Day 1 | FEV1 was measured with spirometry conducted according to internationally accepted standards. Measurements were made in each treatment period at 5, 15, and 30 minutes and 1, 2, and 4 hours post-dose on Day 1. The analysis included baseline FEV1 prior to drug administration in the treatment period as a covariate. | From 5 minutes to 4 hours post-dose on Day 1 | 
| Forced Expiratory Volume in 1 Second (FEV1) by Time Point From 5 Minutes to 12 Hours Post-dose on Day 1 and From 22 to 24 Hours Post-dose on Day 2 | FEV1 was measured with spirometry conducted according to internationally accepted standards. Measurements were made in each treatment period at 5, 15, and 30 minutes and 1, 2, 4, 8, and 12 hours on Day 1 and 22, 23, and 24 hours on Day 2. The analysis included baseline FEV1 prior to drug administration in the treatment period as a covariate. | From 5 minutes to 12 hours post-dose on Day 1 and from 22 to 24 hours post-dose on Day 2 | 
| Forced Expiratory Volume in 1 Second (FEV1) Standardized (With Respect to Time) Area Under the Curve (AUC) From 5 Minutes to 12 Hours Post-dose on Day 1 and From 22 to 24 Hours Post-dose on Day 2 | FEV1 was measured with spirometry conducted according to internationally accepted standards. Measurements were made in each treatment period at 5, 15, and 30 minutes and 1, 2, 4, 8, and 12 hours on Day 1 and 22, 23, and 24 hours on Day 2. Standardized FEV1 AUC was calculated by the trapezoidal rule. The analysis included baseline FEV1 prior to drug administration in the treatment period as a covariate. | From 5 minutes to 12 hours post-dose on Day 1 and from 22 to 24 hours post-dose on Day 2 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
chronic obstructive pulmonary disease, COPD, QAB149, indacaterol, long acting β2-agonist