Efficacy, Safety, Tolerability, and Pharmacokinetics of Indacaterol Salts in Patients With Asthma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT00927901
First received: June 24, 2009
Last updated: August 26, 2013
Last verified: August 2013
  Purpose

This study assessed the efficacy, safety, and pharmacokinetics of indacaterol salts (maleate, xinafoate and acetate) in patients with asthma.


Condition Intervention Phase
Asthma
Drug: Indacaterol maleate 400 μg
Drug: Indacaterol acetate 400 μg
Drug: Indacaterol xinafoate 400 μg
Drug: Placebo to indacaterol
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multi-centre, Randomized, Double-blind, Placebo-controlled, Multiple-dose, 4-way Crossover Study to Evaluate the Efficacy, Safety, Tolerability, and Pharmacokinetics of Orally Inhaled Indacaterol Salts (Maleate, Xinafoate, and Acetate) in Patients With Persistent Asthma

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) 24 Hours Post-dose at the End of Each Treatment Period (Day 7) [ Time Frame: Baseline to the end of each treatment period (Day 7) ] [ Designated as safety issue: No ]
    FEV1 was measured with spirometry conducted according to internationally accepted standards. Trough FEV1 was defined as the average of measurements made 23 hours 10 minutes and 23 hours 45 minutes post-dose at Baseline and at the end of each treatment period. The analysis included period baseline FEV1 as covariate.


Secondary Outcome Measures:
  • Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) 24 Hours Post-dose on Day 1 [ Time Frame: Baseline to Day 1 ] [ Designated as safety issue: No ]
    FEV1 was measured with spirometry conducted according to internationally accepted standards. Trough FEV1 was defined as the average of measurements made 23 hours 10 minutes and 23 hours 45 minutes post-dose at Baseline and on Day 1. The analysis included period baseline FEV1 as covariate.

  • Time to Peak Forced Expiratory Volume in 1 Second (FEV1) on Day 1 and Day 7 [ Time Frame: Day 1 and Day 7 ] [ Designated as safety issue: No ]
    FEV1 was measured with spirometry conducted according to internationally accepted standards at 5, 15, and 30 minutes; 1 hour, 1 hour 30 minutes; and 2, 4, and 12 hours post-dose on Day 1 and Day 7.

  • Percentage of Patients Using Rescue Medication During Each 7 Day Treatment Period [ Time Frame: Baseline to the end of each treatment period (Day 7) ] [ Designated as safety issue: No ]
    Patients recorded use of rescue medication (salbutamol/albuterol multi-dose inhaler) as the number of puffs taken in respective preceding 12 hours morning and evening in a diary. Patient with any use of rescue medication (any number of puffs > 0) was included to calculate endpoint.

  • Indacaterol Exposure (AUC[0-24 Hours]) at the End of Each 7 Day Treatment Period [ Time Frame: End of each treatment period (Day 7) ] [ Designated as safety issue: No ]
    Venous blood samples for pharmacokinetic evaluation were collected at 15 and 30 minutes; and 1, 2, 4, 12, and 24 hours post-dose at the end of each 7 day treatment period and were analyzed using a LC-MS/MS assay. Area under the concentration-time curve up to 24 hours (AUC[0-24 hours]) was calculated from concentration-time data and recorded sampling times using non-compartmental methods.

  • Indacaterol Exposure (Cmax) at the End of Each 7 Day Treatment Period [ Time Frame: End of each treatment period (Day 7) ] [ Designated as safety issue: No ]
    Venous blood samples for pharmacokinetic evaluation were collected at 15 and 30 minutes; and 1, 2, 4, 12, and 24 hours post-dose at the end of each 7 day treatment period and were analyzed using a LC-MS/MS assay. Maximum (peak) plasma drug concentration after drug administration (Cmax) was calculated from concentration-time data and recorded sampling times using non-compartmental methods.


Enrollment: 30
Study Start Date: June 2009
Study Completion Date: November 2009
Primary Completion Date: November 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Indacaterol (ind) maleate-placebo-ind xinafoate-ind acetate
In treatment period 1, patients received indacaterol maleate 400 μg; in treatment period 2, patients received placebo to indacaterol; in treatment period 3, patients received indacaterol xinafoate 400 μg; and in treatment period 4, patients received indacaterol acetate 400 μg. Patients received each treatment once daily for 7 days via the Concept1 single-dose dry-powder inhaler. There was a washout period of at least 7 days between each treatment period. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
Drug: Indacaterol maleate 400 μg
Indacaterol maleate 400 μg was provided in powder filled capsules with the Concept1 single-dose dry-powder inhaler. The dose refers to 400 μg of free base indacaterol.
Drug: Indacaterol acetate 400 μg
Indacaterol acetate 400 μg was provided in powder filled capsules with the Concept1 single-dose dry-powder inhaler. The dose refers to 400 μg of free base indacaterol.
Drug: Indacaterol xinafoate 400 μg
Indacaterol xinafoate 400 μg was provided in powder filled capsules with the Concept1 single-dose dry-powder inhaler. The dose refers to 400 μg of free base indacaterol.
Drug: Placebo to indacaterol
Placebo to indacaterol was provided in powder filled capsules with the Concept1 single-dose dry-powder inhaler.
Experimental: Indacaterol (ind) xinafoate-ind maleate-ind acetate-placebo
In treatment period 1, patients received indacaterol xinafoate 400 μg; in treatment period 2, patients received indacaterol maleate 400 μg; in treatment period 3, patients received indacaterol acetate 400 μg; and in treatment period 4, patients received placebo to indacaterol 400 μg. Patients received each treatment once daily for 7 days via the Concept1 single-dose dry-powder inhaler. There was a washout period of at least 7 days between each treatment period. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
Drug: Indacaterol maleate 400 μg
Indacaterol maleate 400 μg was provided in powder filled capsules with the Concept1 single-dose dry-powder inhaler. The dose refers to 400 μg of free base indacaterol.
Drug: Indacaterol acetate 400 μg
Indacaterol acetate 400 μg was provided in powder filled capsules with the Concept1 single-dose dry-powder inhaler. The dose refers to 400 μg of free base indacaterol.
Drug: Indacaterol xinafoate 400 μg
Indacaterol xinafoate 400 μg was provided in powder filled capsules with the Concept1 single-dose dry-powder inhaler. The dose refers to 400 μg of free base indacaterol.
Drug: Placebo to indacaterol
Placebo to indacaterol was provided in powder filled capsules with the Concept1 single-dose dry-powder inhaler.
Experimental: Indacaterol (ind) acetate-ind xinafoate-placebo-ind maleate
In treatment period 1, patients received indacaterol acetate 400 μg; in treatment period 2, patients received indacaterol xinafoate 400 μg; in treatment period 3, patients received placebo to indacaterol; and in treatment period 4, patients received indacaterol maleate 400 μg. Patients received each treatment once daily for 7 days via the Concept1 single-dose dry-powder inhaler. There was a washout period of at least 7 days between each treatment period. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
Drug: Indacaterol maleate 400 μg
Indacaterol maleate 400 μg was provided in powder filled capsules with the Concept1 single-dose dry-powder inhaler. The dose refers to 400 μg of free base indacaterol.
Drug: Indacaterol acetate 400 μg
Indacaterol acetate 400 μg was provided in powder filled capsules with the Concept1 single-dose dry-powder inhaler. The dose refers to 400 μg of free base indacaterol.
Drug: Indacaterol xinafoate 400 μg
Indacaterol xinafoate 400 μg was provided in powder filled capsules with the Concept1 single-dose dry-powder inhaler. The dose refers to 400 μg of free base indacaterol.
Drug: Placebo to indacaterol
Placebo to indacaterol was provided in powder filled capsules with the Concept1 single-dose dry-powder inhaler.
Experimental: Placebo-indacaterol (ind) acetate-ind maleate-ind xinafoate
In treatment period 1, patients received placebo to indacaterol; in treatment period 2, patients received indacaterol acetate 400 μg; in treatment period 3, patients received indacaterol maleate 400 μg; and in treatment period 4, patients received indacaterol xinafoate 400 μg. Patients received each treatment once daily for 7 days via the Concept1 single-dose dry-powder inhaler. There was a washout period of at least 7 days between each treatment period. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.
Drug: Indacaterol maleate 400 μg
Indacaterol maleate 400 μg was provided in powder filled capsules with the Concept1 single-dose dry-powder inhaler. The dose refers to 400 μg of free base indacaterol.
Drug: Indacaterol acetate 400 μg
Indacaterol acetate 400 μg was provided in powder filled capsules with the Concept1 single-dose dry-powder inhaler. The dose refers to 400 μg of free base indacaterol.
Drug: Indacaterol xinafoate 400 μg
Indacaterol xinafoate 400 μg was provided in powder filled capsules with the Concept1 single-dose dry-powder inhaler. The dose refers to 400 μg of free base indacaterol.
Drug: Placebo to indacaterol
Placebo to indacaterol was provided in powder filled capsules with the Concept1 single-dose dry-powder inhaler.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Non-smoker male and female adult patients aged 18-75 years inclusive, who have signed an informed consent form prior to initiation of any study-related procedure, including any adjustments to asthma medication prior to screening.
  • Patients with asthma, receiving daily treatment with inhaled corticosteroid.
  • Patients with a forced expiratory volume in 1 second (FEV1) during screening of ≥ 50% of the predicted normal value for the patient.
  • Body mass index (BMI) must be within the range 18-32 kg/m^2 (inclusive).
  • Able to communicate well with the investigator and comply with the requirements of the study.

Exclusion criteria:

  • A urine cotinine level greater than the local laboratory lowest level of quantification (LOQ of 500 ng/ml or lower).
  • Patients who have had 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 or any time between screening and pre-dose on day 1 of the study.
  • Patients who have had a respiratory tract infection within 4 weeks prior to screening or any time between screening and pre-dose on day 1 of the study.
  • Patients who require the use of ≥ 8 inhalations per day of the short-acting β2-agonist salbutamol/albuterol (100 μg/90 μg salbutamol/albuterol metered dose inhaler [MDI] or equivalent dose of a dry-powder inhaler [DPI]) on any 2 consecutive days from screening to randomization.
  • Patients diagnosed with chronic obstructive pulmonary disease (COPD) as defined by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines (2008).
  • Participation in any clinical investigation within 4 weeks prior to dosing or longer if required by local regulation. Previous participation in a study with either the investigational or comparator drugs does not exclude a patient from participation in this study.
  • Significant illness.
  • History of being immunocompromised, including a positive human immunodeficiency virus (HIV) test result (ELISA and Western blot).
  • A positive hepatitis B surface antigen (HBsAg) or hepatitis C test result.
  • Patients who are considered vulnerable as per ICH GCP guidelines.
  • Patients with a history of hypersensitivity to indacaterol or to similar drugs including untoward reactions to sympathomimetic amines or inhaled medication or any component thereof.
  • Treatments for asthma and allied conditions:
  • The following treatments should not be used unless they have been stabilized prior to screening: antihistamines, inhaled nasal cromolyn, inhaled nasal corticosteroids, and maintenance immunotherapy.

Other protocol-defined inclusion/exclusion criteria applied to the study.

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00927901

Locations
France
Novartis Investigative Site
Poitiers, France
Germany
Novartis Investigative Site
Wiesbaden, Germany
Italy
Novartis Investigative Site
Verona, Italy
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT00927901     History of Changes
Other Study ID Numbers: CQAB149D2301, 2009-010589-46
Study First Received: June 24, 2009
Results First Received: July 29, 2011
Last Updated: August 26, 2013
Health Authority: Germany: Federal Institute for Drugs and Medical Devices
Italy: Ethics Committee
France: French Health Products Safety Agency (AFSSAPS)

Keywords provided by Novartis:
QAB149
asthma
indacaterol salts (acetate, maleate, and xinafoate)
orally inhaled indacaterol salts
persistent asthma

Additional relevant MeSH terms:
Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Maleic acid
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 17, 2014