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)

• Sponsor: Novartis (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00636961
• Collaborator: (none)
• Enrollment: 27
• Locations: 3
• Arms: 2
• Duration (Months): 6
• Patients Per Site: 9
• Patients Per Site Per Month: 1.5

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Chronic Obstructive Pulmonary Disease	Drug: Indacaterol 300μg; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 27 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, 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
• Study Start Date: Feb 1, 2008
• Actual Primary Completion Date: Aug 1, 2008
• Actual Study Completion Date: Aug 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
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 Names: 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 Names: Arcapta ; Drug: Placebo; Matching placebo devices and hard gelatin capsules

Outcome Measures

Primary Outcome Measures

1. Inspiratory Capacity (IC) at Peak Time and at Isotime on Day 14 [Day 14]

   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

1. Static Inspiratory Capacity (IC) at Day 14 [Day 14]

   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,

2. Trough Forced Expiratory Volume in 1 Second (FEV1) Measured by Spirometry on Day 14 [Day 14]

   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.

3. Chronic Activity Related Breathlessness Measured by Transition Dyspnoea Index (TDI) at Day 14 [Day 14]

   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.

4. Dyspnoea Measured by Borg CR10 Scale at Day 1, Day 14 [Day 1, Day 14]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigator Site	Berlin		Germany
2	Novartis Investigator Site	Mönchengladbach		Germany
3	Novartis Investigator Site	Wiesbaden		Germany

Sponsors and Collaborators

• Novartis

Investigators

• Principal Investigator: Novartis, Novartis investigator site

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00636961
• Other Study ID Numbers: CQAB149B2318
• First Posted: Mar 17, 2008
• Last Update Posted: Aug 30, 2011
• Last Verified: Jul 1, 2011

• Keywords provided by , ,: COPD, Indacaterol Maleate, Exercise testing
• Additional relevant MeSH terms: Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Dyspnea

Study Results

Participant Flow

Arm/Group Title	Sequence 1: Indacaterol 300μg Followed by Placebo	Sequence 2 : Placebo Followed by Indacaterol 300μg
Arm/Group Description	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.	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.
Period Title: Period 1
STARTED	14	13
COMPLETED	13	12
NOT COMPLETED	1	1
Period Title: Period 1
STARTED	13	12
COMPLETED	12	12
NOT COMPLETED	1	0

Baseline Characteristics

Arm/Group Title	Sequence 1: Indacaterol 300μg Followed by Placebo	Sequence 2 : Placebo Followed by Indacaterol 300μg	Total
Arm/Group Description	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.	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.	Total of all reporting groups
Overall Participants	14	13	27
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	62.6 (8.30)	59.8 (5.81)	61.3 (7.22)
Sex: Female, Male (Count of Participants)
Female	4 28.6%	5 38.5%	9 33.3%
Male	10 71.4%	8 61.5%	18 66.7%

Outcome Measures

1. Primary Outcome

Title	Inspiratory Capacity (IC) at Peak Time and at Isotime on Day 14
Description	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.
Time Frame	Day 14

Outcome Measure Data

Analysis Population Description

The safety analysis set consisted of all patients who received study medication and had at least one assessment.

Arm/Group Title	Indacaterol 300ug	Placebo
Arm/Group Description	Patients received indacaterol 300μg via the Concept 1 inhaler device once daily (between 7 am and 12 am) for 2 weeks. Rescue medication (SABA) was prescribed by the investigator for the duration of the study.	Patients received matching placebo via the Concept 1 inhaler device once daily in the morning (between 7 am to 12am) for 2 weeks. Rescue medication (SABA) was prescribed by the investigator for the duration of the study.
Measure Participants	25	25
IC at Peak	2.36	2.05
IC at Isotime	2.37	2.10

2. Secondary Outcome

Title	Static Inspiratory Capacity (IC) at Day 14
Description	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,
Time Frame	Day 14

Outcome Measure Data

Analysis Population Description

The safety analysis set consisted of all patients who received study medication and had at least one assessment.

Arm/Group Title	Indacaterol 300ug	Placebo
Arm/Group Description	Patients received indacaterol 300μg via the Concept 1 inhaler device once daily (between 7 am and 12 am) for 2 weeks. Rescue medication (SABA) was prescribed by the investigator for the duration of the study.	Patients received matching placebo via the Concept 1 inhaler device once daily in the morning (between 7 am to 12am) for 2 weeks. Rescue medication (SABA) was prescribed by the investigator for the duration of the study.
Measure Participants	26	26
Least Squares Mean (90% Confidence Interval) [Liters]	2.55	2.37

3. Secondary Outcome

Title	Trough Forced Expiratory Volume in 1 Second (FEV1) Measured by Spirometry on Day 14
Description	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.
Time Frame	Day 14

Outcome Measure Data

Analysis Population Description

The safety analysis set consisted of all patients who received study medication and had at least one assessment.

Arm/Group Title	Indacaterol 300ug	Placebo
Arm/Group Description	Patients received indacaterol 300μg via the Concept 1 inhaler device once daily (between 7 am and 12 am) for 2 weeks. Rescue medication (SABA) was prescribed by the investigator for the duration of the study.	Patients received matching placebo via the Concept 1 inhaler device once daily in the morning (between 7 am to 12am) for 2 weeks. Rescue medication (SABA) was prescribed by the investigator for the duration of the study.
Measure Participants	25	25
Least Squares Mean (90% Confidence Interval) [Liters]	1.68	1.53

4. Secondary Outcome

Title	Chronic Activity Related Breathlessness Measured by Transition Dyspnoea Index (TDI) at Day 14
Description	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.
Time Frame	Day 14

Outcome Measure Data

Analysis Population Description

The safety analysis set consisted of all patients who received study medication and had at least one assessment.

Arm/Group Title	Indacaterol 300ug	Placebo
Arm/Group Description	Patients received indacaterol 300μg via the Concept 1 inhaler device once daily (between 7 am and 12 am) for 2 weeks. Rescue medication (SABA) was prescribed by the investigator for the duration of the study.	Patients received matching placebo via the Concept 1 inhaler device once daily in the morning (between 7 am to 12am) for 2 weeks. Rescue medication (SABA) was prescribed by the investigator for the duration of the study.
Measure Participants	20	22
Least Squares Mean (90% Confidence Interval) [Score on a scale]	1.0	-2.3

5. Secondary Outcome

Title	Dyspnoea Measured by Borg CR10 Scale at Day 1, Day 14
Description	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.
Time Frame	Day 1, Day 14

Outcome Measure Data

Analysis Population Description

The safety analysis set consisted of all patients who received study medication and had at least one assessment.

Arm/Group Title	Indacaterol 300ug	Placebo
Arm/Group Description	Patients received indacaterol 300μg via the Concept 1 inhaler device once daily (between 7 am and 12 am) for 2 weeks. Rescue medication (SABA) was prescribed by the investigator for the duration of the study.	Patients received matching placebo via the Concept 1 inhaler device once daily in the morning (between 7 am to 12am) for 2 weeks. Rescue medication (SABA) was prescribed by the investigator for the duration of the study.
Measure Participants	26	26
Day 1 : score at Peak (n= 26, 26)	8.2	7.9
Day 14: score at Peak (n= 25, 25)	8.1	8.7
Day 1 : score at Isotime (n= 26, 26)	5.9	5.8
Day 14 : score at Isotime(n= 25, 25)	5.2	6.7

Adverse Events

Adverse Event Reporting Description	The safety analysis set that consisted of all patients who received study medication and had at least one assessment.
Arm/Group Title	Indacaterol 300ug		Placebo
Arm/Group Description	Patients received indacaterol 300μg via the Concept 1 inhaler device once daily (between 7 am and 12 am) for 2 weeks. Rescue medication (SABA) was prescribed by the investigator for the duration of the study.		Patients received matching placebo via the Concept 1 inhaler device once daily in the morning (between 7 am to 12am) for 2 weeks. Rescue medication (SABA) was prescribed by the investigator for the duration of the study.
All Cause Mortality
	Indacaterol 300ug		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Indacaterol 300ug		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/26 (0%)		0/26 (0%)
Other (Not Including Serious) Adverse Events
	Indacaterol 300ug		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/26 (34.6%)		9/26 (34.6%)
Ear and labyrinth disorders
Vertigo	1/26 (3.8%)		0/26 (0%)
Eye disorders
Conjunctivitis allergic	0/26 (0%)		1/26 (3.8%)
Gastrointestinal disorders
Abdominal pain	0/26 (0%)		1/26 (3.8%)
Constipation	0/26 (0%)		1/26 (3.8%)
Diarrhoea	1/26 (3.8%)		1/26 (3.8%)
Dry mouth	0/26 (0%)		1/26 (3.8%)
Tongue coated	0/26 (0%)		1/26 (3.8%)
Infections and infestations
Nasopharyngitis	2/26 (7.7%)		0/26 (0%)
Injury, poisoning and procedural complications
Fall	0/26 (0%)		1/26 (3.8%)
Investigations
Blood pressure increased	0/26 (0%)		1/26 (3.8%)
Electrocardiogram ST segment depression	0/26 (0%)		1/26 (3.8%)
Metabolism and nutrition disorders
Gout	1/26 (3.8%)		0/26 (0%)
Musculoskeletal and connective tissue disorders
Back pain	0/26 (0%)		2/26 (7.7%)
Osteitis	0/26 (0%)		1/26 (3.8%)
Pain in jaw	0/26 (0%)		1/26 (3.8%)
Nervous system disorders
Headache	3/26 (11.5%)		1/26 (3.8%)
Psychiatric disorders
Anxiety	1/26 (3.8%)		0/26 (0%)
Renal and urinary disorders
Nephritis	0/26 (0%)		1/26 (3.8%)
Respiratory, thoracic and mediastinal disorders
Cough	2/26 (7.7%)		0/26 (0%)
Surgical and medical procedures
Tooth extraction	0/26 (0%)		1/26 (3.8%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.