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)

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

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00636961

Enrollment

Registered

2008-03-17

Start date

2008-02-29

Completion date

2008-08-31

Last updated

2011-08-30

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Chronic Obstructive Pulmonary Disease

Keywords

COPD, Indacaterol Maleate, Exercise testing

Brief summary

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

Interventions

DRUGIndacaterol 300μg

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

DRUGPlacebo

Matching placebo devices and hard gelatin capsules

Study design

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

SUPPORTIVE_CARE

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

40 Years to 80 Years

Healthy volunteers

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/

Design outcomes

Primary

Measure	Time frame	Description
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

Measure	Time frame	Description
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,
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.
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.
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.

Countries

Germany

Participant flow

Participants by arm

Arm	Count
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.	14
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.	13
Total	27

Withdrawals & dropouts

Period	Reason	FG000	FG001
Period 1	Administrative problems	1	1
Period 2	Adverse Event	1	0

Baseline characteristics

Characteristic	Sequence 1: Indacaterol 300μg Followed by Placebo	Sequence 2 : Placebo Followed by Indacaterol 300μg	Total
Age Continuous	62.6 years STANDARD_DEVIATION 8.3	59.8 years STANDARD_DEVIATION 5.81	61.3 years STANDARD_DEVIATION 7.22
Sex: Female, Male Female	4 Participants	5 Participants	9 Participants
Sex: Female, Male Male	10 Participants	8 Participants	18 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	9 / 26	9 / 26
serious Total, serious adverse events	0 / 26	0 / 26

Outcome results

Primary

Inspiratory Capacity (IC) at Peak Time and at Isotime on 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.

Time frame: Day 14