Clinical trial NCT02533505: Phase IV O2 Consumption Study in COPD Patients.
Official title: A Phase 4, Randomized, Double-blind, Multicenter, Placebo-Controlled Two Way Cross-Over Study to Evaluate Changes in Oxygen Consumption and Cardiac Function in COPD Patients With Resting Hyperinflation After Administration of Symbicort pMDI 160/4.5 μg.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Chronic Obstructive Pulmonary Disease (COPD)
Keywords: Respiratory
COPD
O2 Consumption
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2015-08-26
Enrollment: 51
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

1. Signing of the informed consent form (ICF) prior to any study specific procedures, including withholding of medications.
2. Male or female, aged 40 to 80 years, inclusive, at Screening (Visit 1).
3. Has a clinical diagnosis of COPD according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2014 guidelines with a post bronchodilator FEV1/FVC \<0.7 at Screening (Visit 1).
4. Has a post-bronchodilator FEV1 ≤65% of predicted value at Screening (Visit 1). National Health and Nutrition Examination Survey (NHANES) predicted normal standards will be used for all subjects.
5. Has an increase in IC of \>10% after the administration of 1 inhalation of open-label Symbicort pMDI administered with a spacer at Screening (Visit 1).
6. Has a cigarette smoking history of more than 10 pack-years (number of cigarettes smoked per day × number of years smoked)/20).
7. Be able to understand and comply with study requirements, as judged by the Investigator.

Exclusion Criteria:

1. Subject is an employee or relative of an employee involved in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
2. Previous enrollment or randomization in this study.
3. Participation in another clinical study with an investigational product (IP) during the last 30 days prior to Screening (Visit 1).
4. Subjects who are unable to discontinue their regular chronic COPD medications (including LAMAs and/or LABA/ICS) and/or who are unable or unwilling to comply with study requirements.
5. Subjects who are taking uLABAs (indacaterol, vilanterol) or uLABA-containing products.
6. Subjects who are taking PDE-4 inhibitors (roflumilast).
7. Subjects who are taking oral corticosteroids on a chronic, regular basis.
8. Subjects using daytime oxygen therapy.
9. Subjects who are currently pregnant (confirmed with positive pregnancy test) or breast feeding.
10. History of respiratory tract infection (including the upper respiratory tract) and/or pulmonary exacerbation within 6 weeks prior to Screening (Visit 1).
11. Pulmonary resection or lung volume reduction surgery within 12 months prior to Screening (Visit 1), or history of lung transplantation, or, in the Investigator's opinion, the subject may need thoracotomy or other lung surgery during the study.
12. History or current diagnosis of asthma and/or alpha 1 anti-trypsin deficiency.
13. Known active tuberculosis.
14. History of interstitial lung or massive pulmonary thromboembolic disease.
15. History of bronchiectasis secondary to respiratory diseases other than COPD (eg, cystic fibrosis, Kartagener's syndrome, etc).
16. Any clinically significant disease or disorder (eg, cardiovascular, gastrointestinal, liver, renal, neurological, musculoskeletal, endocrine, metabolic, psychiatric, major physical impairment) which, in the opinion of the Investigator, may put the subject at risk because of participation in the study, may influence the results of the study, or may affect the subject's ability to participate in the study.
17. Recent (within 12 months prior to Screening \[Visit 1\]) history of myocardial infarction, recent history of heart failure (New York Heart Association \[NYHA\] class III and IV, pulmonary edema, and/or cardiac arrhythmia.
18. Previous or current history of lung cancer.
19. History of cancer (within 5 years prior to Visit 1), except for non-metastatic, non melanoma skin cancer.
20. Subjects who cannot perform spirometry manuevers or tolerate body plethysmography.
21. Subjects with known hypersensitivity to Symbicort, its monocomponents (budesonide or formoterol), or its excipients.

Primary outcomes:
measure: Change From Pre-dose (Visit 2) to Post-dose (Visit 5) Assessment in Oxygen Consumption (VO2; Obtained Via a Metabolic Cart)
timeFrame: 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.
Secondary outcomes:
measure: 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)
timeFrame: 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.
measure: Change From Pre-dose (Visit 2) to Post-dose (Visit 5) Assessment in Gas Exchange Parameter HR
timeFrame: 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.
measure: Change From Pre-dose (Visit 2)to Post-dose (Visit 5) Assessment in Spirometry.
timeFrame: 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.
measure: Change in Vt/Ti
timeFrame: 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.
measure: Change From Pre-dose (Visit 2) to Post-dose (Visit 5) Assessment in the Modified Borg Scale for Dyspnea
timeFrame: 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.
measure: Change From Pre-dose (Visit 2) to Post-dose (Visit 5) Assessment in Gas Exchange Parameter VCO2
timeFrame: 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.
measure: Change From Pre-dose (Visit 2) to Post-dose (Visit 5) Assessment in Gas Exchange Parameter SaO2
timeFrame: 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.
measure: Change in RR
timeFrame: 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.
measure: Change in Ti/Ttot
timeFrame: 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.
measure: Change in Vt
timeFrame: 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.
measure: Change in Ve
timeFrame: 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.
measure: Change From Pre-dose (Visit 2) to Post-dose (Visit 5) Assessment in Spirometry.
timeFrame: 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.
Other outcomes:
Locations:
city: Hartford
country: United States
facility: Research Site
state: Connecticut
city: Boston
country: United States
facility: Research Site
state: Massachusetts
city: Charlotte
country: United States
facility: Research Site
state: North Carolina
city: Philadelphia
country: United States
facility: Research Site
state: Pennsylvania
city: Spartanburg
country: United States
facility: Research Site
state: South Carolina
Study officials:
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