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

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

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).

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: 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

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.

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany
    • Novartis Investigative Site
• Netherlands
  • Groningen, Netherlands
    • Novartis Investigative Site
• United Kingdom
  • Belfast, United Kingdom
    • Novartis Investigative Site
  • Manchester, United Kingdom
    • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) 24 Hours Post-dose for Each Treatment	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.	Baseline and Day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Peak Forced Expiratory Volume in 1 Second (FEV1) for Each Treatment	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.	Baseline and Day 1
Time to Peak Forced Expiratory Volume in 1 Second (FEV1) for Each Treatment	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.	From 5 minutes to 12 hours post-dose
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	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.	From 5 minutes to 4 hours post-dose for each treatment
Indacaterol Exposure (AUC[0-24 Hours]) for Each Treatment	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.	0 to 24 hours post-dose
Indacaterol Exposure (Cmax) for Each Treatment	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.	0 to 24 hours post-dose

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: October 1, 2009
• Primary Completion (Actual): March 1, 2010
• Study Completion (Actual): March 1, 2010

Study Registration Dates

• First Submitted: November 12, 2009
• First Submitted That Met QC Criteria: November 12, 2009
• First Posted (Estimate): November 13, 2009

Study Record Updates

• Last Update Posted (Estimate): August 29, 2011
• Last Update Submitted That Met QC Criteria: August 25, 2011
• Last Verified: August 1, 2011

More Information

Terms related to this study

• Keywords: asthma; pulmonary function; QAB149; indacaterol
• 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: CQAB149B2222; 2009-012600-48 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No