Phase IV O2 Consumption Study in COPD Patients.
Condition: Chronic Obstructive Pulmonary Disease (COPD)
MeSH terms: Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
Intervention: Budesonide 160 mcg and formoterol fumarate dihydrate 4.5 mcg Inhalation aerosol; Matching Placebo pMDI 160/4.5 μg
Intervention description: 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.
Intervention MeSH terms: Budesonide; Formoterol Fumarate
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Enrollment: 51.0
Sex: All
Minimum age: 40 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: Respiratory; COPD; O2 Consumption

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.
    

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.