Efficacy, Safety, Tolerability, and Pharmacokinetics of Indacaterol Maleate Via Concept1 or Simoon Devices

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01012739
First received: November 12, 2009
Last updated: August 25, 2011
Last verified: August 2011
  Purpose

This study assessed the efficacy, safety, tolerability, and pharmacokinetics of two different formulations of indacaterol, one administered via the Concept1 device and one administered via the Simoon device. The study aimed to determine whether the novel formulation (Simoon) had a similar profile to that of the established formulation (Concept1).


Condition Intervention Phase
Asthma
Drug: Indacaterol 150 μg via the Concept1 dry-powder inhaler
Drug: Indacaterol 60 μg via the Simoon dry-powder inhaler
Drug: Indacaterol 120 μg via the Simoon dry-powder inhaler
Drug: Placebo to indacaterol via the Concept1 dry-powder inhaler
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Partially-blinded, Single-dose, 4-way Cross-over Study to Evaluate the Efficacy, Safety, Tolerability, and Pharmacokinetics of Orally Inhaled Indacaterol Maleate Administered Via the Concept1 Device or Via the Simoon Device

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 for Each Treatment [ Time Frame: Baseline and 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 for each treatment.


Secondary Outcome Measures:
  • Change From Baseline in Peak Forced Expiratory Volume in 1 Second (FEV1) for Each Treatment [ Time Frame: Baseline and Day 1 ] [ Designated as safety issue: No ]
    FEV1 was measured with spirometry conducted according to internationally accepted standards. Measurements were made at 5, 15, and 30 minutes; and 1, 2, 4, 6, 8, and 12 hours post-dose in Day 1.

  • Time to Peak Forced Expiratory Volume in 1 Second (FEV1) for Each Treatment [ Time Frame: From 5 minutes to 12 hours post-dose ] [ 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 1, 2, 4, 6, 8, and 12 hours post-dose in Day 1.

  • Forced Expiratory Volume in 1 Second (FEV1) Standardized (With Respect to Length of Time) Area Under the Curve (AUC) From 5 Minutes to 4 Hours Post-dose for Each Treatment [ Time Frame: From 5 minutes to 4 hours post-dose for each treatment ] [ Designated as safety issue: No ]
    FEV1 was measured with spirometry conducted according to internationally accepted standards. Measurements were made at 5, 15, and 30 minutes; and 1, 2, and 4 hours post-dose. The standardized AUC FEV1 was calculated as the sum of trapezoids divided by the length of time.

  • Indacaterol Exposure (AUC[0-24 Hours]) for Each Treatment [ Time Frame: 0 to 24 hours post-dose ] [ Designated as safety issue: No ]
    All patients fasted for at least 10 hours prior to administration of study medication and continued to fast for at least 4 hours thereafter. Venous blood samples for pharmacokinetic evaluation were collected at 5, 10, 15, and 30 minutes; and 1, 2, 4, 8, and 24 hours post-dose in each 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 using non-compartmental analysis.

  • Indacaterol Exposure (Cmax) for Each Treatment [ Time Frame: 0 to 24 hours post-dose ] [ Designated as safety issue: No ]
    All patients fasted for at least 10 hours prior to administration of study medication and continued to fast for at least 4 hours thereafter. Venous blood samples for pharmacokinetic evaluation were collected at 5, 10, 15, and 30 minutes; and 1, 2, 4, 8, and 24 hours post-dose in each 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 using non-compartmental analysis.


Enrollment: 35
Study Start Date: October 2009
Study Completion Date: March 2010
Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Indacaterol 150μg-placebo-Indacaterol 60μg-Indacaterol 120μg
In treatment period 1, patients received indacaterol 150 μg via the Concept1 dry-powder inhaler (DPI); in treatment period 2, patients received placebo to indacaterol via the Concept1 DPI; in treatment period 3, patients received indacaterol 60 μg via the Simoon DPI; and in treatment period 4, patients received indacaterol 120 μg via the Simoon DPI. Patients received each treatment only once. There was a washout period of 14-17 days between treatments for patients undergoing pharmacokinetic (PK) assessments; for patients not undergoing PK assessments, the washout period was 7-10 days. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol was available for rescue use throughout the study.
Drug: Indacaterol 150 μg via the Concept1 dry-powder inhaler
Indacaterol maleate 150 μg was provided in powder filled capsules with the Concept1 dry-powder inhaler.
Drug: Indacaterol 60 μg via the Simoon dry-powder inhaler
Indacaterol 60 μg was provided in powder filled capsules with the Simoon dry-powder inhaler.
Drug: Indacaterol 120 μg via the Simoon dry-powder inhaler
Indacaterol 120 μg was provided in powder filled capsules with the Simoon dry-powder inhaler.
Drug: Placebo to indacaterol via the Concept1 dry-powder inhaler
Placebo to indacaterol was provided in powder filled capsules with the Concept1 dry-powder inhaler.
Experimental: Indacaterol 60μg-Indacaterol 150μg-Indacaterol 120μg-placebo
In treatment period 1, patients received indacaterol 60 μg via the Simoon dry-powder inhaler (DPI); in treatment period 2, patients received indacaterol 150 μg via the Concept1 DPI; in treatment period 3, patients received indacaterol 120 μg via the Simoon DPI; and in treatment period 4, patients received placebo to indacaterol via the Concept1 DPI. Patients received each treatment only once. There was a washout period of 14-17 days between treatments for patients undergoing pharmacokinetic (PK) assessments; for patients not undergoing PK assessments, the washout period was 7-10 days. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol was available for rescue use throughout the study.
Drug: Indacaterol 150 μg via the Concept1 dry-powder inhaler
Indacaterol maleate 150 μg was provided in powder filled capsules with the Concept1 dry-powder inhaler.
Drug: Indacaterol 60 μg via the Simoon dry-powder inhaler
Indacaterol 60 μg was provided in powder filled capsules with the Simoon dry-powder inhaler.
Drug: Indacaterol 120 μg via the Simoon dry-powder inhaler
Indacaterol 120 μg was provided in powder filled capsules with the Simoon dry-powder inhaler.
Drug: Placebo to indacaterol via the Concept1 dry-powder inhaler
Placebo to indacaterol was provided in powder filled capsules with the Concept1 dry-powder inhaler.
Experimental: Indacaterol 120μg-Indacaterol 60μg-placebo-Indacaterol 150μg
In treatment period 1, patients received indacaterol 120 μg via the Simoon dry-powder inhaler (DPI); in treatment period 2, patients received indacaterol 60 μg via the Simoon DPI; in treatment period 3, patients received placebo to indacaterol via the Concept1 DPI; and in treatment period 4, patients received indacaterol 150 μg via the Concept1 DPI. Patients received each treatment only once. There was a washout period of 14-17 days between treatments for patients undergoing pharmacokinetic (PK) assessments; for patients not undergoing PK assessments, the washout period was 7-10 days. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol was available for rescue use throughout the study.
Drug: Indacaterol 150 μg via the Concept1 dry-powder inhaler
Indacaterol maleate 150 μg was provided in powder filled capsules with the Concept1 dry-powder inhaler.
Drug: Indacaterol 60 μg via the Simoon dry-powder inhaler
Indacaterol 60 μg was provided in powder filled capsules with the Simoon dry-powder inhaler.
Drug: Indacaterol 120 μg via the Simoon dry-powder inhaler
Indacaterol 120 μg was provided in powder filled capsules with the Simoon dry-powder inhaler.
Drug: Placebo to indacaterol via the Concept1 dry-powder inhaler
Placebo to indacaterol was provided in powder filled capsules with the Concept1 dry-powder inhaler.
Experimental: Placebo-Indacaterol 120μg- Indacaterol 150μg- Indacaterol 60μg
In treatment period 1, patients received placebo to indacaterol via the Concept1 dry-powder inhaler (DPI); in treatment period 2, patients received indacaterol 120 μg via the Simoon DPI; in treatment period 3, patients received indacaterol 150 μg via the Concept1 DPI; and in treatment period 4, patients received indacaterol 60 μg via the Simoon DPI. Patients received each treatment only once. There was a washout period of 14-17 days between treatments for patients undergoing pharmacokinetic (PK) assessments; for patients not undergoing PK assessments, the washout period was 7-10 days. Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol was available for rescue use throughout the study.
Drug: Indacaterol 150 μg via the Concept1 dry-powder inhaler
Indacaterol maleate 150 μg was provided in powder filled capsules with the Concept1 dry-powder inhaler.
Drug: Indacaterol 60 μg via the Simoon dry-powder inhaler
Indacaterol 60 μg was provided in powder filled capsules with the Simoon dry-powder inhaler.
Drug: Indacaterol 120 μg via the Simoon dry-powder inhaler
Indacaterol 120 μg was provided in powder filled capsules with the Simoon dry-powder inhaler.
Drug: Placebo to indacaterol via the Concept1 dry-powder inhaler
Placebo to indacaterol was provided in powder filled capsules with the Concept1 dry-powder inhaler.

Detailed Description:

This study was double-blind with regards to the Concept1, where placebo for the lactose-blended indacaterol was available. However, with regards to the Simoon, neither the subject nor the investigator was blinded due to lack of a placebo to the PulmoSphere formulation. Hence, the overall designation of the study was partially-blind.

  Eligibility

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

Inclusion criteria:

  • Patients with persistent asthma with a forced expiratory volume in 1 second (FEV1) ≥ 50%
  • Patients using inhaled corticosteroid (with or without long-acting beta agonist)

Exclusion criteria:

  • Asthma exacerbations in previous 6 months
  • Chronic obstructive pulmonary disease (COPD) or other pulmonary disease
  • Excessive use of short-acting beta agonists

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

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01012739

Locations
Germany
Novartis Investigative Site
Berlin, Germany
Netherlands
Novartis Investigative Site
Groningen, Netherlands
United Kingdom
Novartis Investigative Site
Belfast, United Kingdom
Novartis Investigative Site
Manchester, United Kingdom
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: NCT01012739     History of Changes
Other Study ID Numbers: CQAB149B2222, 2009-012600-48
Study First Received: November 12, 2009
Results First Received: July 22, 2011
Last Updated: August 25, 2011
Health Authority: Germany: Federal Institute for Drugs and Medical Devices
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Novartis:
asthma
QAB149
indacaterol
pulmonary function

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 August 01, 2014