Dose Ranging Study for Indacaterol in Japanese Asthma Patients

Study Overview
=================
Brief Summary
-----------------
This study was designed to provide data about the safety and efficacy of 3 doses of indacaterol (150, 300, and 600 µg) in Japanese asthma patients so that an optimal dose, or doses, could be chosen for testing in later studies.

Official Title
-----------------
A Randomized, Double-blind, Placebo-controlled, 4-period 4-treatment Crossover, Multicenter, Single-dose, Dose-ranging Study Followed by a Single Day's Treatment With Open Label Salmeterol Bid (100 µg/Day), to Assess the Efficacy and Safety of 3 Doses of Indacaterol (150, 300, & 600 µg) Delivered Via Single Dose Dry Powder Inhaler (SDDPI) in Japanese Asthma Patients

Conditions
-----------------
Asthma

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


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male and female Japanese asthmatic patients aged 18 to 75 years old. Exclusion Criteria: Patients who have been hospitalized or had emergency room treatment for an acute asthma attack in the 6 months prior to the first day of screening or during the screening period. Patients who have used tobacco products within 6 months prior to the first day of screening or have a smoking history of greater than 10 pack years. Patients with a history of malignancy with the exception of localized basal cell carcinoma of the skin. Pregnant or nursing (lactating) women. Patients who have had treatment with disallowed medications including investigational drug. Other protocol-defined inclusion/exclusion criteria applied to the study.

Ages Eligible for Study
-----------------
Minimum Age: 18 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Placebo-Ind 150 μg-Ind 300 μg-Ind 600 μg-Salmeterol<br>In treatment period 1: patients received 2 placebo capsules; in treatment period 2: patients received 1 indacaterol (Ind) 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. Two inhalation capsules of study drug were inhaled using a single dose dry powder inhaler (SDDPI) in the morning on day 1 of each treatment period at approximately the same time of day +/- 15 minutes. There was a washout period of 14-28 days between each treatment period. In open label treatment period 5: patients received 100 μg salmeterol (50 μg in the morning, 50 μg twelve hours post initial dose) inhaled via Diskus®, an inhalation device, on Day 1. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) salbutamol was available for rescue use throughout the study. | Drug: Indacaterol<br>* In the morning, powder filled capsules inhaled using a single dose dry powder inhaler (SDDPI).<br>* Other names: QAB149;Drug: Placebo<br>* Placebo to indacaterol was provided in powder filled capsules with a single dose dry powder inhaler (SDDPI).<br>Drug: Salmeterol<br>* Salmeterol 100 μg total dose taken on Day 1. 50 μg in the morning and 50 μg twelve hours post initial dose inhaled via Diskus®, an inhalation device for Salmeterol.<br>* Other names: Serevent;|
| Experimental: Ind 150 μg-Ind 600 μg-Placebo-Ind 300 μg-Salmeterol<br>In treatment period 1: patients received 1 indacaterol (Ind) 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. Two inhalation capsules of study drug were inhaled using a single dose dry powder inhaler (SDDPI) in the morning on day 1 of each treatment period at approximately the same time of day +/- 15 minutes. There was a washout period of 14-28 days between each treatment period. In open label treatment period 5: patients received 100 μg salmeterol (50 μg in the morning, 50 μg twelve hours post initial dose) inhaled via Diskus®, an inhalation device, on Day 1. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) salbutamol was available for rescue use throughout the study. | Drug: Indacaterol<br>* In the morning, powder filled capsules inhaled using a single dose dry powder inhaler (SDDPI).<br>* Other names: QAB149;Drug: Placebo<br>* Placebo to indacaterol was provided in powder filled capsules with a single dose dry powder inhaler (SDDPI).<br>Drug: Salmeterol<br>* Salmeterol 100 μg total dose taken on Day 1. 50 μg in the morning and 50 μg twelve hours post initial dose inhaled via Diskus®, an inhalation device for Salmeterol.<br>* Other names: Serevent;|
| Experimental: Ind 300 μg-Placebo-Ind 600 μg-Ind 150 μg-Salmeterol<br>In treatment period 1: patients received 1 indacaterol (Ind) 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. Two inhalation capsules of study drug were inhaled using a single dose dry powder inhaler (SDDPI) in the morning on day 1 of each treatment period at approximately the same time of day +/- 15 minutes. There was a washout period of 14-28 days between each treatment period. In open label treatment period 5: patients received 100 μg salmeterol (50 μg in the morning, 50 μg twelve hours post initial dose) inhaled via Diskus®, an inhalation, device on Day 1. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) salbutamol was available for rescue use throughout the study. | Drug: Indacaterol<br>* In the morning, powder filled capsules inhaled using a single dose dry powder inhaler (SDDPI).<br>* Other names: QAB149;Drug: Placebo<br>* Placebo to indacaterol was provided in powder filled capsules with a single dose dry powder inhaler (SDDPI).<br>Drug: Salmeterol<br>* Salmeterol 100 μg total dose taken on Day 1. 50 μg in the morning and 50 μg twelve hours post initial dose inhaled via Diskus®, an inhalation device for Salmeterol.<br>* Other names: Serevent;|
| Experimental: Ind 600 μg-Ind 300 μg-Ind 150 μg-Placebo-Salmeterol<br>In treatment period 1: patients received 2 indacaterol (Ind) 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. Two inhalation capsules of study drug were inhaled using a single dose dry powder inhaler (SDDPI) in the morning on day 1 of each treatment period at approximately the same time of day +/- 15 minutes. There was a washout period of 14-28 days between each treatment period. In open label treatment period 5: patients received 100 μg salmeterol (50 μg in the morning, 50 μg twelve hours post initial dose) inhaled via Diskus®, an inhalation device, on Day 1. Daily inhaled corticosteroid treatment (if applicable) was allowed to remain stable throughout the study. The short acting (beta) β2-agonist (SABA) salbutamol was available for rescue use throughout the study. | Drug: Indacaterol<br>* In the morning, powder filled capsules inhaled using a single dose dry powder inhaler (SDDPI).<br>* Other names: QAB149;Drug: Placebo<br>* Placebo to indacaterol was provided in powder filled capsules with a single dose dry powder inhaler (SDDPI).<br>Drug: Salmeterol<br>* Salmeterol 100 μg total dose taken on Day 1. 50 μg in the morning and 50 μg twelve hours post initial dose inhaled via Diskus®, an inhalation device for Salmeterol.<br>* Other names: Serevent;|

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 | Spirometry was conducted according to internationally accepted standards. Standardized area under the curve (AUC22-24h) of FEV1 values taken at 22, 23 and 24 hours post dose, was calculated based on the trapezoidal rule. Analysis of Covariance was carried out with a mixed model that used (period) baseline, defined as the value of FEV1 measured prior to the first study drug intake in the period, as a covariate. | 22, 23, and 24 hours post-dose on Day 2 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | Spirometry was conducted according to internationally accepted standards. FEV1 by time point was calculated using a mixed model with (period) baseline, defined as the value measured prior to the first study drug intake in the period, as a covariate. | 5, 15, and 30 minutes; and 1, 2, 4, 8, and 12 hours post-dose on Day 1; and 22, 23, and 24 hours post-dose on Day 2 | 
| Peak Forced Expiratory Volume in 1 Second (FEV1) From 5 Minutes to 4 Hours Post-dose on Day 1 | Spirometry was conducted according to internationally accepted standards. Peak FEV1 is the maximum FEV1 recorded in the period between 5 minutes and 4 hours post dose. Analysis of Covariance was carried out with a mixed model that used (period) baseline, defined as the value of FEV1 measured prior to the first study drug intake in the period, as a covariate. | 5 minutes to 4 hours post-dose on Day 1 | 
| Forced Expiratory Volume in 1 Second (FEV1) Standardized (With Respect to Time) Area Under the Curve (AUC) From 5 Minutes Post-dose on Day 1 to 24 Hours Post-dose on Day 2 | Spirometry was conducted according to internationally accepted standards. Standardized area under the curve (AUC0-24h) of FEV1 values taken at pre-dose to 24 hours post dose was calculated based on the trapezoidal rule. Analysis of Covariance was carried out with a mixed model that used (period) baseline, defined as the value of FEV1 measured prior to the first study drug intake in the period, as a covariate. | 5 minutes to 12 hours post-dose on Day 1; and 22 to 24 hours post-dose on Day 2 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
asthma, QAB149, indacaterol, long acting β2-agonist, bronchodilator