Efficacy, Safety and Pharmacokinetics of Different Regimens of Indacaterol

A Multi-center, Randomized, Double-blind, Placebo-controlled, Parallel Group, Repeated-dose Study to Evaluate the Efficacy, Safety, Tolerability, and Pharmacokinetics of Three Different Dosing Regimens of Inhaled Indacaterol Maleate in Patients With Persistent Asthma

This study assessed the bronchodilator efficacy of three different regimens of indacaterol in patients with asthma

Study Overview

• Status: Completed
• Conditions: Persistent Asthma
• Intervention / Treatment: Drug: Indacaterol; Drug: Placebo to Indacaterol

• Study Type: Interventional
• Enrollment (Actual): 191
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Paris, France
    • Novartis Investigative Site
  • Rennes, France
    • Novartis Investigative Site
• Germany
  • Wiesbaden, Germany
    • Novartis Investigative Site
• Jordan
  • Amman, Jordan
    • Novartis Investigative Site
  • Irbid, Jordan
    • Novartis Investigative Site
• Netherlands
  • Groningen, Netherlands
    • Novartis Investigative Site
• United Kingdom
  • London, United Kingdom
    • Novartis Investigative Site
  • Manchester, United Kingdom
    • Novartis Investigative Site
  • Merthyr Tydfil, United Kingdom
    • Novartis Investigative Site
• United States
  • Alabama
    • Anniston, Alabama, United States, 36207
      • Novartis Investigative Site
  • California
    • Cypress, California, United States, 90630
      • Novartis Investigative Site
    • Fresno, California, United States, 93726
      • Novartis Investigative Site
    • San Diego, California, United States, 92120
      • Novartis Investigative Site
  • Colorado
    • Denver, Colorado, United States, 80206
      • Novartis Investigative Site
  • Florida
    • Clearwater, Florida, United States, 33756
      • Novartis Investigative Site
    • Miami, Florida, United States, 33175
      • Novartis Investigative Site
    • Miami, Florida, United States, 33167
      • Novartis Investigative Site
    • Sarasota, Florida, United States, 34233
      • Novartis Investigative Site
    • Tampa, Florida, United States, 33617
      • Novartis Investigative Site
  • Illinois
    • Normal, Illinois, United States, 61761
      • Novartis Investigative Site
  • Louisiana
    • Lafayette, Louisiana, United States, 70503
      • Novartis Investigative Site
  • Nevada
    • Las Vegas, Nevada, United States, 89119
      • Novartis Investigative Site
  • New Jersey
    • Berlin, New Jersey, United States, 08009
      • Novartis Investigative Site
  • North Carolina
    • Raleigh, North Carolina, United States, 27607
      • Novartis Investigative Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73120
      • Novartis Investigator Site
  • Texas
    • Houston, Texas, United States, 77070
      • Novartis Investigative Site
    • Plano, Texas, United States, 75075
      • Novartis Investigative Site
    • San Antonio, Texas, United States, 78212
      • Novartis Investigative Site
  • Washington
    • Tacoma, Washington, United States, 98405
      • Novartis Investigative Site
    • Tacoma, Washington, United States, 98418
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with a diagnosis of asthma and:
• Receiving daily treatment with inhaled corticosteroid in a regimen that has been stable for at least a month prior to screening
• FEV1 ≥50% and ≤90% of predicted normal at screening
• An increase of ≥12% and ≥200 mL in FEV1 over prebronchodilator value within 30 minutes after inhaling a total dose of albuterol/salbutamol of 360/400 MDI

Exclusion Criteria:

• Smoking history of ≥ 10 years
• Patients with a diagnosis of COPD
• Patients who have been previously intubated for a severe asthma exacerbation/ attack
• Patients who have experienced a severe asthma attack/exacerbation requiring hospitalization in the 6 months prior to screening
• Patients who have had an emergency room visit for an asthma attack/exacerbation within 6 weeks prior to screening
• Patients who have had a respiratory tract infection within 6 weeks prior to screening
• Patients with seasonal allergy whose asthma is likely to deteriorate during the study period
• Patients with Type I or uncontrolled Type II diabetes mellitus

Other protocol-defined inclusion/exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Indacaterol 37.5 µg (twice a day); Indacaterol 37.5 µg twice a day (bid) inhaled via Concept1, a single dose dry powder inhaler (SDDPI), in the morning and in the evening for 16 days. All patients had to receive daily treatment with inhaled corticosteroid up to the maximum dose per day in a stable regimen for at least 4-weeks prior to screening and remain stable through out the study. The short acting (beta) β2-agonist (SABA) salbutamol/albuterol was available for rescue use throughout the study.	Drug: Indacaterol; Indacaterol inhaled via Concept1, a single dose dry powder inhaler (SDDPI) for 16 days. Dosage and frequency varied according to randomization scheme.
Experimental: Indacaterol 75 µg (once a day); Indacaterol 75 µg once a day (qd) inhaled via Concept1, a single dose dry powder inhaler (SDDPI), in the morning and Placebo to Indacaterol inhaled once daily via Concept1 in the evening for 16 days. All patients had to receive daily treatment with inhaled corticosteroid up to the maximum dose per day in a stable regimen for at least 4-weeks prior to screening and remain stable through out the study. The short acting (beta) β2-agonist (SABA) salbutamol/albuterol was available for rescue use throughout the study.	Drug: Indacaterol; Indacaterol inhaled via Concept1, a single dose dry powder inhaler (SDDPI) for 16 days. Dosage and frequency varied according to randomization scheme.; Drug: Placebo to Indacaterol; Placebo inhaled via Concept1, a SDDPI. Frequency varied according to randomization scheme.
Experimental: Indacaterol 150 µg (every other day); Indacaterol 150 µg every other day (qod) inhaled via Concept1, a single dose dry powder inhaler (SDDPI) for a total of 16 days. Indacaterol 150 µg inhaled via Concept1, a SDDPI, in the morning and Placebo to Indacaterol inhaled via Concept1 in the evening on odd days; and Placebo to Indacaterol inhaled via Concept1 in the morning and in the evening on even days. All patients had to receive daily treatment with inhaled corticosteroid up to the maximum dose per day in a stable regimen for at least 4-weeks prior to screening and remain stable through out the study. The short acting (beta) β2-agonist (SABA) salbutamol/albuterol was available for rescue use throughout the study.	Drug: Indacaterol; Indacaterol inhaled via Concept1, a single dose dry powder inhaler (SDDPI) for 16 days. Dosage and frequency varied according to randomization scheme.; Drug: Placebo to Indacaterol; Placebo inhaled via Concept1, a SDDPI. Frequency varied according to randomization scheme.
Placebo Comparator: Placebo; Placebo to Indacaterol twice daily (bid) inhaled via Concept1, a single dose dry powder inhaler (SDDPI), in the morning and in the evening for 16 days. All patients had to receive daily treatment with inhaled corticosteroid up to the maximum dose per day in a stable regimen for at least 4-weeks prior to screening and remain stable through out the study. The short acting (beta) β2-agonist (SABA) salbutamol/albuterol was available for rescue use throughout the study.	Drug: Placebo to Indacaterol; Placebo inhaled via Concept1, a SDDPI. Frequency varied according to randomization scheme.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in the Trough Forced Expiratory Volume in One Second (FEV1) After Two Weeks of Treatment	Spirometry was conducted according to internationally accepted standards. Trough FEV1 values were calculated as the mean of the 23.17 hours and 23.75 hours post morning dose FEV1 measurements. Analysis of covariance model was used with baseline FEV1 as a continuous covariate.	Baseline to week 2
Change From Baseline in the Forced Expiratory Volume in 1 Second Standardized (With Respect to Time) Area Under the Curve (AUC) From 0 to 24 Hours Post Dose (FEV1 AUC 0-24h) After Two Weeks of Treatment	Spirometry was conducted according to internationally accepted standards. Standardized area under the curve (AUC 0-24 hours) of FEV1 measurements taken at pre-dose to 24 hours post-dose was calculated based on the trapezoidal rule and was adjusted for the area per time unit using the scheduled time of measurements for FEV1. Analysis of covariance model was used with baseline FEV1 as a continuous covariate.	Baseline, 0-24 hours post dose week 2
Change From Baseline in the Forced Expiratory Volume in 1 Second Standardized (With Respect to Time) Area Under the Curve (AUC) From 0 to 48 Hours (FEV1 AUC 0-48h) After Two Weeks of Treatment	Spirometry was conducted according to internationally accepted standards. Standardized area under the curve (AUC 0-48 hours) of FEV1 measurements taken at pre-dose to 48 hours post-dose was calculated based on the trapezoidal rule and was adjusted for the area per time unit by using the scheduled time of measurements for FEV1. Analysis of covariance model was used with baseline FEV1 as a continuous covariate.	Baseline, 0 to 48 hours post dose week 2

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in the Forced Expiratory Volume in 1 Second Standardized (With Respect to Time) Area Under the Curve (AUC) From 0 to 12 Hours (FEV1 AUC 0-12h) After Two Weeks of Treatment	Spirometry was conducted according to internationally accepted standards. Standardized area under the curve (AUC 0-12 hours) of FEV1 measurements taken at pre-dose to 12 hours post-dose was calculated based on the trapezoidal rule and was adjusted for the area per time unit by using the scheduled time of measurements for FEV1. Analysis of covariance model was used with baseline FEV1 as a continuous covariate.	Baseline, 0 to 12 hours post dose week 2

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: March 1, 2010
• Primary Completion (Actual): July 1, 2010

Study Registration Dates

• First Submitted: June 30, 2010
• First Submitted That Met QC Criteria: July 2, 2010
• First Posted (Estimate): July 5, 2010

Study Record Updates

• Last Update Posted (Estimate): August 17, 2011
• Last Update Submitted That Met QC Criteria: July 22, 2011
• Last Verified: July 1, 2011

More Information

Terms related to this study

• Keywords: Asthma; Indacaterol; Bronchodilation; Beta-agonist
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma
• Other Study ID Numbers: CQAB149B2223; 2010-018481-22 (EudraCT Number)