Trial Outcomes & Findings for 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) (NCT NCT00636961)
NCT ID: NCT00636961
Last Updated: 2011-08-30
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
27 participants
Primary outcome timeframe
Day 14
Results posted on
2011-08-30
Participant Flow
Participant milestones
| Measure |
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.
|
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.
|
|---|---|---|
|
Period 1
STARTED
|
14
|
13
|
|
Period 1
COMPLETED
|
13
|
12
|
|
Period 1
NOT COMPLETED
|
1
|
1
|
|
Period 2
STARTED
|
13
|
12
|
|
Period 2
COMPLETED
|
12
|
12
|
|
Period 2
NOT COMPLETED
|
1
|
0
|
Reasons for withdrawal
| Measure |
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.
|
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.
|
|---|---|---|
|
Period 1
Administrative problems
|
1
|
1
|
|
Period 2
Adverse Event
|
1
|
0
|
Baseline Characteristics
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)
Baseline characteristics by cohort
| Measure |
Sequence 1: Indacaterol 300μg Followed by Placebo
n=14 Participants
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.
|
Sequence 2 : Placebo Followed by Indacaterol 300μg
n=13 Participants
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
n=27 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age Continuous
|
62.6 years
STANDARD_DEVIATION 8.30 • n=5 Participants
|
59.8 years
STANDARD_DEVIATION 5.81 • n=7 Participants
|
61.3 years
STANDARD_DEVIATION 7.22 • n=5 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
10 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
18 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Day 14Population: The safety analysis set consisted of all patients who received study medication and had at least one assessment.
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.
Outcome measures
| Measure |
Indacaterol 300ug
n=25 Participants
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.
|
Placebo
n=25 Participants
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.
|
|---|---|---|
|
Inspiratory Capacity (IC) at Peak Time and at Isotime on Day 14
IC at Peak
|
2.36 Liters
Interval 2.25 to 2.48
|
2.05 Liters
Interval 1.93 to 2.16
|
|
Inspiratory Capacity (IC) at Peak Time and at Isotime on Day 14
IC at Isotime
|
2.37 Liters
Interval 2.25 to 2.48
|
2.10 Liters
Interval 1.99 to 2.21
|
SECONDARY outcome
Timeframe: Day 14Population: The safety analysis set consisted of all patients who received study medication and had at least one assessment.
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,
Outcome measures
| Measure |
Indacaterol 300ug
n=26 Participants
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.
|
Placebo
n=26 Participants
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.
|
|---|---|---|
|
Static Inspiratory Capacity (IC) at Day 14
|
2.55 Liters
Interval 2.46 to 2.65
|
2.37 Liters
Interval 2.28 to 2.47
|
SECONDARY outcome
Timeframe: Day 14Population: The safety analysis set consisted of all patients who received study medication and had at least one assessment.
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.
Outcome measures
| Measure |
Indacaterol 300ug
n=25 Participants
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.
|
Placebo
n=25 Participants
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.
|
|---|---|---|
|
Trough Forced Expiratory Volume in 1 Second (FEV1) Measured by Spirometry on Day 14
|
1.68 Liters
Interval 1.59 to 1.76
|
1.53 Liters
Interval 1.45 to 1.62
|
SECONDARY outcome
Timeframe: Day 14Population: The safety analysis set consisted of all patients who received study medication and had at least one assessment.
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.
Outcome measures
| Measure |
Indacaterol 300ug
n=20 Participants
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.
|
Placebo
n=22 Participants
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.
|
|---|---|---|
|
Chronic Activity Related Breathlessness Measured by Transition Dyspnoea Index (TDI) at Day 14
|
1.0 Score on a scale
Interval -0.3 to 2.4
|
-2.3 Score on a scale
Interval -3.6 to -1.0
|
SECONDARY outcome
Timeframe: Day 1, Day 14Population: The safety analysis set consisted of all patients who received study medication and had at least one assessment.
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.
Outcome measures
| Measure |
Indacaterol 300ug
n=26 Participants
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.
|
Placebo
n=26 Participants
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.
|
|---|---|---|
|
Dyspnoea Measured by Borg CR10 Scale at Day 1, Day 14
Day 1 : score at Peak (n= 26, 26)
|
8.2 Score on a scale
Interval 7.4 to 8.9
|
7.9 Score on a scale
Interval 7.2 to 8.7
|
|
Dyspnoea Measured by Borg CR10 Scale at Day 1, Day 14
Day 14: score at Peak (n= 25, 25)
|
8.1 Score on a scale
Interval 7.5 to 8.8
|
8.7 Score on a scale
Interval 8.1 to 9.4
|
|
Dyspnoea Measured by Borg CR10 Scale at Day 1, Day 14
Day 1 : score at Isotime (n= 26, 26)
|
5.9 Score on a scale
Interval 5.0 to 6.7
|
5.8 Score on a scale
Interval 4.9 to 6.6
|
|
Dyspnoea Measured by Borg CR10 Scale at Day 1, Day 14
Day 14 : score at Isotime(n= 25, 25)
|
5.2 Score on a scale
Interval 4.4 to 6.0
|
6.7 Score on a scale
Interval 5.9 to 7.5
|
Adverse Events
Indacaterol 300ug
Serious events: 0 serious events
Other events: 9 other events
Deaths: 0 deaths
Placebo
Serious events: 0 serious events
Other events: 9 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Indacaterol 300ug
n=26 participants at risk
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.
|
Placebo
n=26 participants at risk
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.
|
|---|---|---|
|
Ear and labyrinth disorders
Vertigo
|
3.8%
1/26
The safety analysis set that consisted of all patients who received study medication and had at least one assessment.
|
0.00%
0/26
The safety analysis set that consisted of all patients who received study medication and had at least one assessment.
|
|
Eye disorders
Conjunctivitis allergic
|
0.00%
0/26
The safety analysis set that consisted of all patients who received study medication and had at least one assessment.
|
3.8%
1/26
The safety analysis set that consisted of all patients who received study medication and had at least one assessment.
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/26
The safety analysis set that consisted of all patients who received study medication and had at least one assessment.
|
3.8%
1/26
The safety analysis set that consisted of all patients who received study medication and had at least one assessment.
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/26
The safety analysis set that consisted of all patients who received study medication and had at least one assessment.
|
3.8%
1/26
The safety analysis set that consisted of all patients who received study medication and had at least one assessment.
|
|
Gastrointestinal disorders
Diarrhoea
|
3.8%
1/26
The safety analysis set that consisted of all patients who received study medication and had at least one assessment.
|
3.8%
1/26
The safety analysis set that consisted of all patients who received study medication and had at least one assessment.
|
|
Gastrointestinal disorders
Dry mouth
|
0.00%
0/26
The safety analysis set that consisted of all patients who received study medication and had at least one assessment.
|
3.8%
1/26
The safety analysis set that consisted of all patients who received study medication and had at least one assessment.
|
|
Gastrointestinal disorders
Tongue coated
|
0.00%
0/26
The safety analysis set that consisted of all patients who received study medication and had at least one assessment.
|
3.8%
1/26
The safety analysis set that consisted of all patients who received study medication and had at least one assessment.
|
|
Infections and infestations
Nasopharyngitis
|
7.7%
2/26
The safety analysis set that consisted of all patients who received study medication and had at least one assessment.
|
0.00%
0/26
The safety analysis set that consisted of all patients who received study medication and had at least one assessment.
|
|
Injury, poisoning and procedural complications
Fall
|
0.00%
0/26
The safety analysis set that consisted of all patients who received study medication and had at least one assessment.
|
3.8%
1/26
The safety analysis set that consisted of all patients who received study medication and had at least one assessment.
|
|
Investigations
Blood pressure increased
|
0.00%
0/26
The safety analysis set that consisted of all patients who received study medication and had at least one assessment.
|
3.8%
1/26
The safety analysis set that consisted of all patients who received study medication and had at least one assessment.
|
|
Investigations
Electrocardiogram ST segment depression
|
0.00%
0/26
The safety analysis set that consisted of all patients who received study medication and had at least one assessment.
|
3.8%
1/26
The safety analysis set that consisted of all patients who received study medication and had at least one assessment.
|
|
Metabolism and nutrition disorders
Gout
|
3.8%
1/26
The safety analysis set that consisted of all patients who received study medication and had at least one assessment.
|
0.00%
0/26
The safety analysis set that consisted of all patients who received study medication and had at least one assessment.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/26
The safety analysis set that consisted of all patients who received study medication and had at least one assessment.
|
7.7%
2/26
The safety analysis set that consisted of all patients who received study medication and had at least one assessment.
|
|
Musculoskeletal and connective tissue disorders
Osteitis
|
0.00%
0/26
The safety analysis set that consisted of all patients who received study medication and had at least one assessment.
|
3.8%
1/26
The safety analysis set that consisted of all patients who received study medication and had at least one assessment.
|
|
Musculoskeletal and connective tissue disorders
Pain in jaw
|
0.00%
0/26
The safety analysis set that consisted of all patients who received study medication and had at least one assessment.
|
3.8%
1/26
The safety analysis set that consisted of all patients who received study medication and had at least one assessment.
|
|
Nervous system disorders
Headache
|
11.5%
3/26
The safety analysis set that consisted of all patients who received study medication and had at least one assessment.
|
3.8%
1/26
The safety analysis set that consisted of all patients who received study medication and had at least one assessment.
|
|
Psychiatric disorders
Anxiety
|
3.8%
1/26
The safety analysis set that consisted of all patients who received study medication and had at least one assessment.
|
0.00%
0/26
The safety analysis set that consisted of all patients who received study medication and had at least one assessment.
|
|
Renal and urinary disorders
Nephritis
|
0.00%
0/26
The safety analysis set that consisted of all patients who received study medication and had at least one assessment.
|
3.8%
1/26
The safety analysis set that consisted of all patients who received study medication and had at least one assessment.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
7.7%
2/26
The safety analysis set that consisted of all patients who received study medication and had at least one assessment.
|
0.00%
0/26
The safety analysis set that consisted of all patients who received study medication and had at least one assessment.
|
|
Surgical and medical procedures
Tooth extraction
|
0.00%
0/26
The safety analysis set that consisted of all patients who received study medication and had at least one assessment.
|
3.8%
1/26
The safety analysis set that consisted of all patients who received study medication and had at least one assessment.
|
Additional Information
Study Director
Novartis Pharmaceuticals
Phone: 862-778-8300
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER