A Phase IV study evaluating changes in oxygen consumption and cardiac function in Subjects with Chronic obstructive pulmonary disease (COPD) with resting hyperinflation after administration of Symbicort pMDI 160/4.5 μg.
Patients with moderate/severe COPD are known to have static hyperinflation and to develop dynamic hyperinflation during exercise. Treatment with inhaled long-acting beta agonists and combination of the long-acting beta agonist (LABA), formoterol and the inhaled corticosteroid, budesonide has been shown to improve IC and decrease lung hyperinflation. In a similar previous pilot single centre study with budesonide/formoterol (Symbicort®) the analysis of cardiac outcomes demonstrated a decrease in maximum volume of oxygen (VO2) compared to placebo. Findings suggested that the use of Symbicort can decrease the cost of breathing and therefore reduce the cardiac demand experienced by COPD patients with hyperinflation at rest. The aim of this study is to investigate whether Symbicort therapy can decrease resting VO2 by decreasing static lung hyperinflation in subjects with COPD and to evaluate changes in cardiac function.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
51
Subjects will receive a single dose (2 inhalations) of Symbicort pMDI 160/4.5 μg (2 inhalations; total dosage 320/9.0 μg) or placebo (with a spacer) in a cross-over design (a total of 2 doses of Symbicort and 2 doses of placebo over the duration of the study), and assessments will be made before and after dosing at specified timepoints
Placebo will be given according at the same dose and schedule as the active comparator - cross-over design.
Research Site
Hartford, Connecticut, United States
Research Site
Boston, Massachusetts, United States
Research Site
Charlotte, North Carolina, United States
Research Site
Philadelphia, Pennsylvania, United States
Change From Pre-dose (Visit 2) to Post-dose (Visit 5) Assessment in Oxygen Consumption (VO2; Obtained Via a Metabolic Cart)
For all outcome measures, treatment group estimates are LS Means across visits (change between 2 or more time points, calculated as the value at the later time point minus the value at the earlier time point, e.g. LS means across visits up to Visit 5 minus pre-dose Visit 2 value). Estimate for difference = LS Mean (Symbicort pMDI 160mcg/4.5ug) - LS Mean (placebo).
Time frame: Assessment (60 minutes pre and post dose) at Visit 2 (Day 0), Visit 3 (Day 7), Visit 4 (Day 14), and Visit 5 (Day 21); change from baseline pre-dose to Day 21 post-dose reported.
Change From Pre-dose (Visit 2) to Post-dose (Visit 5) Assessment in Oxygen Pulse (Defined as VO2/Heart Rate [HR]; VO2 is Obtained Via a Metabolic Cart; Used as a Surrogate for Stroke Volume)
For all outcome measures, treatment group estimates are LS Means across visits (change between 2 or more time points, calculated as the value at the later time point minus the value at the earlier time point, e.g. LS means across visits up to Visit 5 minus pre-dose Visit 2 value). Estimate for difference = LS Mean (Symbicort pMDI 160mcg/4.5ug) - LS Mean (placebo).
Time frame: Assessment (60 minutes pre and post dose) at Visit 2 (Day 0), Visit 3 (Day 7), Visit 4 (Day 14), and Visit 5 (Day 21); change from baseline pre-dose to Day 21 post-dose reported.
Change From Pre-dose (Visit 2) to Post-dose (Visit 5) Assessment in Gas Exchange Parameter HR
For all outcome measures, treatment group estimates are LS Means across visits (change between 2 or more time points, calculated as the value at the later time point minus the value at the earlier time point, e.g. LS means across visits up to Visit 5 minus pre-dose Visit 2 value). Estimate for difference = LS Mean (Symbicort pMDI 160mcg/4.5ug) - LS Mean (placebo).
Time frame: Assessment (60 minutes pre and post dose) at Visit 2 (Day 0), Visit 3 (Day 7), Visit 4 (Day 14), and Visit 5 (Day 21); change from baseline pre-dose to Day 21 post-dose reported.
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Research Site
Spartanburg, South Carolina, United States
Change From Pre-dose (Visit 2)to Post-dose (Visit 5) Assessment in Spirometry.
Forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), and IC (using an slow vital capacity \[SVC\] maneuver; IC/total lung capacity \[TLC\] will be used as a measure of resting hyperinflation). For all outcome measures, treatment group estimates are LS Means across visits (change between 2 or more time points, calculated as the value at the later time point minus the value at the earlier time point, e.g. LS means across visits up to Visit 5 minus pre-dose Visit 2 value). Estimate for difference = LS Mean (Symbicort pMDI 160mcg/4.5ug) - LS Mean (placebo).
Time frame: Assessment (60 minutes pre and post dose) at Visit 2 (Day 0), Visit 3 (Day 7), Visit 4 (Day 14), and Visit 5 (Day 21); change from baseline pre-dose to Day 21 post-dose reported.
Change in Vt/Ti
Change from pre-dose (Visit 2) to post-dose (Visit 5) assessment in mean inspiratory flow (tidal volume \[Vt\]/inspiratory time \[Ti\]). For all outcome measures, treatment group estimates are LS Means across visits (change between 2 or more time points, calculated as the value at the later time point minus the value at the earlier time point, e.g. LS means across visits up to Visit 5 minus pre-dose Visit 2 value). Estimate for difference = LS Mean (Symbicort pMDI 160mcg/4.5ug) - LS Mean (placebo).
Time frame: Assessment (60 minutes pre and post dose) at Visit 2 (Day 0), Visit 3 (Day 7), Visit 4 (Day 14), and Visit 5 (Day 21); change from baseline pre-dose to Day 21 post-dose reported.
Change From Pre-dose (Visit 2) to Post-dose (Visit 5) Assessment in the Modified Borg Scale for Dyspnea
For all outcome measures, treatment group estimates are LS Means across visits (change between 2 or more time points, calculated as the value at the later time point minus the value at the earlier time point, e.g. LS means across visits up to Visit 5 minus pre-dose Visit 2 value). Estimate for difference = LS Mean (Symbicort pMDI 160mcg/4.5ug) - LS Mean (placebo). Modified Borg scale for dyspnea was self-administered at Visit 2 (Day 0), Visit 3 (Day 7), Visit 4 (Day 14), and Visit 5 (Day 21). The Borg scale is a 1-item instrument through which a subject reports dyspnea symptoms on a scale of 0-10 to quantify the intensity of dyspnea (where 10 is most intense).
Time frame: Assessment (60 minutes pre and post dose) at Visit 2 (Day 0), Visit 3 (Day 7), Visit 4 (Day 14), and Visit 5 (Day 21); change from baseline pre-dose to Day 21 post-dose reported.
Change From Pre-dose (Visit 2) to Post-dose (Visit 5) Assessment in Gas Exchange Parameter VCO2
For all outcome measures, treatment group estimates are LS Means across visits (change between 2 or more time points, calculated as the value at the later time point minus the value at the earlier time point, e.g. LS means across visits up to Visit 5 minus pre-dose Visit 2 value). Estimate for difference = LS Mean (Symbicort pMDI 160mcg/4.5ug) - LS Mean (placebo).
Time frame: Assessment (60 minutes pre and post dose) at Visit 2 (Day 0), Visit 3 (Day 7), Visit 4 (Day 14), and Visit 5 (Day 21); change from baseline pre-dose to Day 21 post-dose reported.
Change From Pre-dose (Visit 2) to Post-dose (Visit 5) Assessment in Gas Exchange Parameter SaO2
For all outcome measures, treatment group estimates are LS Means across visits (change between 2 or more time points, calculated as the value at the later time point minus the value at the earlier time point, e.g. LS means across visits up to Visit 5 minus pre-dose Visit 2 value). Estimate for difference = LS Mean (Symbicort pMDI 160mcg/4.5ug) - LS Mean (placebo).
Time frame: Assessment (60 minutes pre and post dose) at Visit 2 (Day 0), Visit 3 (Day 7), Visit 4 (Day 14), and Visit 5 (Day 21); change from baseline pre-dose to Day 21 post-dose reported.
Change in RR
For all outcome measures, treatment group estimates are LS Means across visits (change between 2 or more time points, calculated as the value at the later time point minus the value at the earlier time point, e.g. LS means across visits up to Visit 5 minus pre-dose Visit 2 value). Estimate for difference = LS Mean (Symbicort pMDI 160mcg/4.5ug) - LS Mean (placebo).
Time frame: Assessment (60 minutes pre and post dose) at Visit 2 (Day 0), Visit 3 (Day 7), Visit 4 (Day 14), and Visit 5 (Day 21); change from baseline pre-dose to Day 21 post-dose reported.
Change in Ti/Ttot
Change from pre-dose (Visit 2) to post-dose (Visit 5) assessment in fractional inspiratory time (Ti/total cycle time \[Ttot\]). For all outcome measures, treatment group estimates are LS Means across visits (change between 2 or more time points, calculated as the value at the later time point minus the value at the earlier time point, e.g. LS means across visits up to Visit 5 minus pre-dose Visit 2 value). Estimate for difference = LS Mean (Symbicort pMDI 160mcg/4.5ug) - LS Mean (placebo).
Time frame: Assessment (60 minutes pre and post dose) at Visit 2 (Day 0), Visit 3 (Day 7), Visit 4 (Day 14), and Visit 5 (Day 21); change from baseline pre-dose to Day 21 post-dose reported.
Change in Vt
Change from pre-dose (Visit 2) to post-dose (Visit 5) assessment in tidal volume (Vt). For all outcome measures, treatment group estimates are LS Means across visits (change between 2 or more time points, calculated as the value at the later time point minus the value at the earlier time point, e.g. LS means across visits up to Visit 5 minus pre-dose Visit 2 value). Estimate for difference = LS Mean (Symbicort pMDI 160mcg/4.5ug) - LS Mean (placebo).
Time frame: Assessment (60 minutes pre and post dose) at Visit 2 (Day 0), Visit 3 (Day 7), Visit 4 (Day 14), and Visit 5 (Day 21); change from baseline pre-dose to Day 21 post-dose reported.
Change in Ve
Change from pre-dose (Visit 2) to post-dose (Visit 5) assessment in minute ventilation (Ve). For all outcome measures, treatment group estimates are LS Means across visits (change between 2 or more time points, calculated as the value at the later time point minus the value at the earlier time point, e.g. LS means across visits up to Visit 5 minus pre-dose Visit 2 value). Estimate for difference = LS Mean (Symbicort pMDI 160mcg/4.5ug) - LS Mean (placebo).
Time frame: Assessment (60 minutes pre and post dose) at Visit 2 (Day 0), Visit 3 (Day 7), Visit 4 (Day 14), and Visit 5 (Day 21); change from baseline pre-dose to Day 21 post-dose reported.
Change From Pre-dose (Visit 2) to Post-dose (Visit 5) Assessment in Spirometry.
FEV1/FVC. For all outcome measures, treatment group estimates are LS Means across visits (change between 2 or more time points, calculated as the value at the later time point minus the value at the earlier time point, e.g. LS means across visits up to Visit 5 minus pre-dose Visit 2 value). Estimate for difference = LS Mean (Symbicort pMDI 160mcg/4.5ug) - LS Mean (placebo).
Time frame: Assessment (60 minutes pre and post dose) at Visit 2 (Day 0), Visit 3 (Day 7), Visit 4 (Day 14), and Visit 5 (Day 21); change from baseline pre-dose to Day 21 post-dose reported.