Chronic Obstructive Pulmonary Disease (COPD) Clinical Trial
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.
Verified date | July 2018 |
Source | AstraZeneca |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
Status | Completed |
Enrollment | 51 |
Est. completion date | August 12, 2016 |
Est. primary completion date | August 12, 2016 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 40 Years to 80 Years |
Eligibility |
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. |
Country | Name | City | State |
---|---|---|---|
United States | Research Site | Boston | Massachusetts |
United States | Research Site | Charlotte | North Carolina |
United States | Research Site | Hartford | Connecticut |
United States | Research Site | Philadelphia | Pennsylvania |
United States | Research Site | Spartanburg | South Carolina |
Lead Sponsor | Collaborator |
---|---|
AstraZeneca |
United States,
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* Note: There are 17 references in all — Click here to view all references
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | 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). | 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 | 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). | 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 | 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). | 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 | 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). | 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 | 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). | 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 | 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). | 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 | 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). | 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 | 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). | 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 | 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). | 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 | 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). | 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 | 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). | 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 | 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). | 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 | 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). | 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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