A Study to Evaluate the Effects of Indacaterol Maleate (QAB149) as a New Formulation in the EPIC Test Fixture

A Randomized, Double-blind, Double-dummy, Placebo-controlled, 3-period Crossover Study to Evaluate the Pharmacodynamics, Pharmacokinetics, Safety and Tolerability of Orally Inhaled Indacaterol Administered Via the EPIC Test Fixture and the Concept1 Device in Adult Patients With Persistent Asthma

This study will assess the pharmacodynamics, safety, tolerability and pharmacokinetics of indacaterol maleate (QAB149), administered via the EPIC test fixture. The study aims to determine whether the novel device has a similar clinical profile as the established concept 1 device.

Study Overview

• Status: Withdrawn
• Conditions: Asthma
• Intervention / Treatment: Drug: QAB149 75 mg Concept 1; Other: Placebo EPIC Test Fixture; Drug: QAB149 75 mg Epic Test Fixture; Other: Placebo Concept 1

• Study Type: Interventional
• Phase: Phase 2

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:

Male and female patients with asthma, aged 18 or above Patients using inhaled corticosteroid (with or without long acting beta agonist) Patients who demonstrate an increase in FEV1 after inhaling a short acting beta agonist

Exclusion Criteria:

Asthma exacerbations in previous 6 months COPD or other pulmonary disease Excessive use of short acting beta agonists

Other protocol-defined inclusion/exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment B	Drug: QAB149 75 mg Epic Test Fixture; QAB149 delivered via the EPIC test fixture; Other: Placebo Concept 1; Placebo administered via the Concept 1 device.
Experimental: Treatment A	Drug: QAB149 75 mg Concept 1; QAB149 delivered via the concept 1 device.; Other: Placebo EPIC Test Fixture; Placebo administered via the EPIC Test Fixture.
Placebo Comparator: Treatment C	Other: Placebo EPIC Test Fixture; Placebo administered via the EPIC Test Fixture.; Other: Placebo Concept 1; Placebo administered via the Concept 1 device.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Trough Forced Expiratory Volume in 1 Second (FEV1) Following 3 Days of Treatment	FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation, measured through spirometry testing. The trough in FEV1 was defined as the mean of two measurements at 23h 10min and 23h 45min post the Day 3 dose.	Day 4

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peak Forced Expiratory Volume in 1 Second (FEV1) on Days 1 and 3	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 on Days 1 and 3.	Days 1 and 3
Time to Peak Forced Expiratory Volume in 1 Second (FEV1) on Days 1 and 3	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 on Days 1 and 3.	Days 1 and 3
Forced Vital Capacity (FVC) at Each Time-point on Day 1, 2, 3 and 4	Spirometry was conducted according to internationally accepted standards. FVC was calculated at each time point up to 4 hours post-dose and at 23 hours 10 min and 23 hours 45 min on Days 1/2 and 3/4.	Days 1, 2, 3 and 4
Forced Expiratory Volume in 1 Second (FEV1) Standardized (With Respect to Length of Time) Area Under the Curve (AUC) From pre-dose to 4 hours post dose on Days 1 and 3	FEV1 was measured with spirometry conducted according to internationally accepted standards. Measurements were made at 5, 15, and 30 minutes; and 1, 2, 3 and 4 hours post-dose. The standardized AUC FEV1 was calculated as the sum of trapezoids divided by the length of time.	Days 1 and 3
Peak Expiratory Flow Rate measured daily each morning and evening.	Peak Expiratory Flow (PEF) was measured every morning and evening from screening until study completion using a peak flow meter, and was recorded in the patient diary.	Morning and evening from screening to study completion (up to 86 days)
Forced Expiratory Volume in 1 Second (FEV1)	Spirometry was conducted according to internationally accepted standards. Forced expiratory volume in 1 second (FEV1) is the amount of air that can be exhaled in one second. FEV1 was measured at each time point up to 4 hours on Days 1 and 3 and at 23hours 10 mins and 23 hours 45 mins on Days 2 and 4.	Days 1, 2, 3 and 4
Ratio of Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) (FEV1/FVC	Spirometry was conducted according to internationally accepted standards. FEV1/FVC represents the proportion of the total amount of air that is exhaled from the lungs during the first second of forced exhalation. FEV1/FVC was measured at each timepoint up to 4 hours on Days 1 and 3 and 23hours 10mins and 23hours 45 mins on Days 2 and 4.	Days 1, 2, 3, 4
Forced expiratory Flow 25-75% (FEF25-75%)	The forced expiratory flow (FEF) 25%-75% measurement describes the amount of air expelled from the lungs during the middle half (25% - 75%) of the forced vital capacity test and is measured using spirometry. FEF 25-75% was measured at each timepoint up to 4 hours on Days 1 and 3 and 23hours 10mins and 23hours 45 mins on Days 2 and 4	Days 1, 2, 3, 4
Number of puffs of rescue medication used	Participants maintained a diary to record the daily number of puffs of rescue Short-acting B2 agonist (SABA) used to treat asthma symptoms.	Everyday from screening to study completion (up to 86 days)
The number of participants with adverse events used as a measure of Safety and Tolerability	Safety and tolerability of indacaterol administered via the EPIC test fixture and the Concept1 was measured by collecting the following safety data: - number and percentage of adverse events reported by participants for the duration of the study - safety laboratory testing - measurement of vital signs (blood pressure and heart rate) - measurement of ECGs	Baseline to study completion (up to 59 days)
AUC (0-24) - area under the serum concentration-time curve	The PK parameter AUC0-24 - area under the serum concentration-time curve - was determined from the serum concentration time profile of indacaterol on Days 1 and 3 from time zero to 24 hours post dose using a non-compartmental method	Day 1 and Day 3 (pre-dose, 5, 15, 30 mins, 1, 2, 4, 8, 12, 24hours post dose
Cmax - observed maximum serum concentration following drug administration	The PK parameter Cmax - observed maximum serum concentration following drug administration - was determined from the serum concentration time profile of indacaterol on Days 1 and 3 using a non-compartmental method.	Day 1 and Day 3 (pre-dose, 5, 15, 30 mins, 1, 2, 4, 8, 12, 24hours post dose
Tmax - time to reach maximum concentration after drug administration	The PK parameter Tmax - time to reach maximum concentration after drug administration - was determined from the serum concentration time profile of indacaterol on Days 1 and 3 using a non-compartmental method.	Day 1 and Day 3 (pre-dose, 5, 15, 30 mins, 1, 2, 4, 8, 12, 24hours post dose
Racc - accumulation ratio of exposure (AUC0-24 and Cmax) on Day 3 relative to Day 1	The PK parameter Racc - accumulation ratio of exposure (AUC0-24 and Cmax) on Day 3 relative to Day 1 - was determined from the serum concentration time profile of indacaterol on Days 1 and 3 using a non-compartmental method.	Day 1 and Day 3 (pre-dose, 5, 15, 30 mins, 1, 2, 4, 8, 12, 24hours post dose
Trough Forced Expiratory Volume in 1 Second (FEV1) Following 1 Day of Treatment	FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation, measured through spirometry testing. The trough in FEV1 was defined as the mean of two measurements at 23h 10min and 23h 45min post the Day 1 dose.	Day 2

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: August 1, 2013
• Primary Completion (Anticipated): December 1, 2013
• Study Completion (Anticipated): December 1, 2013

Study Registration Dates

• First Submitted: April 17, 2013
• First Submitted That Met QC Criteria: May 1, 2013
• First Posted (Estimate): May 3, 2013

Study Record Updates

• Last Update Posted (Actual): April 20, 2017
• Last Update Submitted That Met QC Criteria: April 19, 2017
• Last Verified: July 1, 2013

More Information

Terms related to this study

• Keywords: Asthma; 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: CMID001A2201; 2011-001824-39 (EudraCT Number)