An Exploratory Study, to Assess the Effect of Repeat-dose Inhaled Indacaterol Maleate (300 μg) on Dynamic and Static Lung Hyperinflation, Subjective Breathlessness and Health Status in Patients With Chronic Obstructive Pulmonary Disease(COPD) - Full Text View

Purpose

This study evaluated the effect of QAB149 on dynamic and static hyperinflation, breathlessness, and health status in COPD patients

Condition	Intervention	Phase
Chronic Obstructive Pulmonary Disease	Drug: Indacaterol 300μg Drug: Placebo	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Crossover Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Supportive Care
Official Title:	An Exploratory, Double Blind, Randomized, Placebo-controlled, 2-way Cross-over Study to Assess the Effect of Repeat-dose Inhaled Indacaterol Maleate (300 μg) on Dynamic and Static Lung Hyperinflation, Subjective Breathlessness and Health Status in Patients With COPD

Resource links provided by NLM:

MedlinePlus related topics: Breathing Problems COPD (Chronic Obstructive Pulmonary Disease)

Drug Information available for: Indacaterol Indacaterol maleate

U.S. FDA Resources

Further study details as provided by Novartis:

Primary Outcome Measures:

Inspiratory Capacity (IC) at Peak Time and at Isotime on Day 14 [ Time Frame: Day 14 ] [ Designated as safety issue: No ]
Inspiratory capacity (IC) at peak time and at isotime were the primary pharmacodynamic (PD) variables of interest. IC was measured at two minute intervals during exercise. Isotime was defined as the time the subject was still exercising in the shortest of all sub-maximal exercise tests (3-minutes resting pedaling, 3-minutes unloaded pedaling and exercise with loaded pedaling). Peak time was defined as the last measurement taken in the exercise period. The primary analysis consisted of a linear mixed effects model with baseline IC measurement as covariate.

Secondary Outcome Measures:

Static Inspiratory Capacity (IC) at Day 14 [ Time Frame: Day 14 ] [ Designated as safety issue: No ]
Inspiratory Capacity (IC) at resting (static IC) was measured by using whole body plethysmography. The day 14 measurement was analyzed using an analysis of variance including baseline (day -2) as a covariate,
Trough Forced Expiratory Volume in 1 Second (FEV1) Measured by Spirometry on Day 14 [ Time Frame: Day 14 ] [ 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. The linear mixed model included the baseline FEV1 measurement as covariate.
Chronic Activity Related Breathlessness Measured by Transition Dyspnoea Index (TDI) at Day 14 [ Time Frame: Day 14 ] [ Designated as safety issue: No ]
Dyspnoea was measured during the treatment period using the transition dyspnoea index (TDI), which captures changes from baseline. The TDI has three domains; functional impairment, magnitude of task and magnitude of effort. TDI domains are rated from -3 (major deterioration) to 3 (major improvement) and rates are summed for transition focal score ranging from -9 to 9; minus scores indicate deterioration. A TDI focal score of 1 was considered to be a clinically significant and meaningful improvement from baseline. Analysis of variance included period baseline dyspnoea index (BDI) as covariate.
Dyspnoea Measured by Borg CR10 Scale at Day 1, Day 14 [ Time Frame: Day 1, Day 14 ] [ Designated as safety issue: No ]
The modified Borg CR10 Scale consists of 12-point score that the patients point to so as to indicate their level of dyspnoea (where 0 indicates no breathlessness at all to 12 indicates maximum breathlessness), before and during exercise testing. A reduction in this score indicates an improvement. Isotime was defined as the time the subject was still exercising in the shortest of all sub-maximal exercise tests. Peak time was defined as the last measurement taken in the exercise period. Analysis of variance included period, treatment and sequence as fixed effects and subject as random effect.

Enrollment:	27
Study Start Date:	February 2008
Study Completion Date:	August 2008
Primary Completion Date:	August 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Sequence 1: Indacaterol 300μg followed by Placebo In period I, indacaterol 300μg was taken by inhalation once daily via the Concept 1 inhaler device for 2 weeks. In period II, matching placebo was taken by inhalation once daily via the Concept 1 inhaler device for 2 weeks. For each treatment period and for each patient, the doses were to be administered between 7am and 12am. A period of at least 4 days but no more than 21 days separated each treatment period. Rescue medication (short-acting beta-agonist (SABA)) was prescribed by the investigator for the duration of the study.	Drug: Indacaterol 300μg 300μg indacaterol maleate inhalation powder in hard gelatin capsules administered via Concept1 inhalation device Other Name: Arcapta Drug: Placebo Matching placebo devices and hard gelatin capsules
Experimental: Sequence 2 : Placebo followed by Indacaterol 300μg In period I, matching placebo was taken by inhalation once daily via the Concept 1 inhaler device for 2 weeks. In period II, indacaterol 300μg was taken by inhalation once daily via the Concept 1 inhaler device for 2 weeks. For each treatment period and for each patient, the doses were to be administered between 7am and 12am. A period of at least 4 days but no more than 21 days separated each treatment period. Rescue medication (short-acting beta-agonist (SABA)) was prescribed by the investigator for the duration of the study.	Drug: Indacaterol 300μg 300μg indacaterol maleate inhalation powder in hard gelatin capsules administered via Concept1 inhalation device Other Name: Arcapta Drug: Placebo Matching placebo devices and hard gelatin capsules

Arms

Assigned Interventions

Experimental: Sequence 1: Indacaterol 300μg followed by Placebo

In period I, indacaterol 300μg was taken by inhalation once daily via the Concept 1 inhaler device for 2 weeks. In period II, matching placebo was taken by inhalation once daily via the Concept 1 inhaler device for 2 weeks. For each treatment period and for each patient, the doses were to be administered between 7am and 12am. A period of at least 4 days but no more than 21 days separated each treatment period. Rescue medication (short-acting beta-agonist (SABA)) was prescribed by the investigator for the duration of the study.

Drug: Indacaterol 300μg

300μg indacaterol maleate inhalation powder in hard gelatin capsules administered via Concept1 inhalation device

Other Name: Arcapta

Drug: Placebo

Matching placebo devices and hard gelatin capsules

Experimental: Sequence 2 : Placebo followed by Indacaterol 300μg

In period I, matching placebo was taken by inhalation once daily via the Concept 1 inhaler device for 2 weeks. In period II, indacaterol 300μg was taken by inhalation once daily via the Concept 1 inhaler device for 2 weeks. For each treatment period and for each patient, the doses were to be administered between 7am and 12am. A period of at least 4 days but no more than 21 days separated each treatment period. Rescue medication (short-acting beta-agonist (SABA)) was prescribed by the investigator for the duration of the study.

Drug: Indacaterol 300μg

300μg indacaterol maleate inhalation powder in hard gelatin capsules administered via Concept1 inhalation device

Other Name: Arcapta

Drug: Placebo

Matching placebo devices and hard gelatin capsules

Eligibility

Ages Eligible for Study:	40 Years to 80 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Male and female subjects,
40 to 80 years of age,
with a documented diagnosis of mild, moderate or severe chronic obstructive pulmonary disease (COPD) according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria and >20-pack year history of smoking, a post-bronchodilator 40% ≤ FEV1 ≤ 80% of predicted normal and post-bronchodilator FEV1/FVC < 70% who have signed an informed consent form (ICF) prior to the initiation of any study-related procedure (Post bronchodilator refers to 30 minutes after the inhalation of 400 µg of salbutamol)
Subjects who demonstrate a plethysmographic functional residual capacity >120% predicted normal

Exclusion Criteria:

No COPD exacerbations within 6 weeks prior to dosing,
no concomitant lung disease such as asthma,
no requirement for long term oxygen treatment or history of lung reduction surgery.
No medical conditions that would interfere with the performance of spirometry or clinical exercise testing.
Any other medical condition that in the opinion of the investigator may cause the patient to be unsuitable for completion of the study or place the patient at potential risk from participating in the study e.g. uncontrolled hypertension or unstable ischemic heart disease

Other protocol-defined inclusion/exclusion criteria may apply

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00636961

Locations

Germany
Novartis Investigator Site
Berlin, Germany
Novartis Investigator Site
Mönchengladbach, Germany
Novartis Investigator Site
Wiesbaden, Germany

Sponsors and Collaborators

Novartis

Investigators

Principal Investigator:

Novartis

Novartis investigator site

More Information

No publications provided

Responsible Party:	External Affairs, Novartis
ClinicalTrials.gov Identifier:	NCT00636961 History of Changes
Other Study ID Numbers:	CQAB149B2318
Study First Received:	March 10, 2008
Results First Received:	July 29, 2011
Last Updated:	July 29, 2011
Health Authority:	Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Novartis:

COPD, Indacaterol Maleate, Exercise testing

Additional relevant MeSH terms:

Dyspnea
Lung Diseases
Respiration Disorders
Pulmonary Disease, Chronic Obstructive
Lung Diseases, Obstructive
Respiratory Tract Diseases

Signs and Symptoms, Respiratory
Signs and Symptoms
Maleic acid
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 21, 2013