Chronic Obstructive Pulmonary Disease (COPD)Phase 4NCT02533505
Phase IV O2 Consumption Study in COPD Patients.
A Phase 4 study testing Budesonide 160 mcg and formoterol fumarate dihydrate 4.5 mcg Inhalation aerosol in people with Chronic Obstructive Pulmonary Disease (COPD), run by AstraZeneca at 5 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 40 to 80 years
- Conditions the study is for
- Chronic Obstructive Pulmonary Disease (COPD)
- What is being tested?
- Budesonide 160 mcg and formoterol fumarate dihydrate 4.5 mcg Inhalation aerosol
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 51 participants
- Where
- 5 sitesUnited States
- Study dates
- 25 Aug 2015to 12 Aug 2016
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Signing of the informed consent form (ICF) prior to any study specific procedures, including withholding of medications.
- Male or female, aged 40 to 80 years, inclusive, at Screening (Visit 1).
- 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).
- 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.
- 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).
- Has a cigarette smoking history of more than 10 pack-years (number of cigarettes smoked per day × number of years smoked)/20).
- Be able to understand and comply with study requirements, as judged by the Investigator.
Who cannot join
- 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).
- Previous enrollment or randomization in this study.
- Participation in another clinical study with an investigational product (IP) during the last 30 days prior to Screening (Visit 1).
- 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.
- Subjects who are taking uLABAs (indacaterol, vilanterol) or uLABA-containing products.
- Subjects who are taking PDE-4 inhibitors (roflumilast).
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- Subjects who are taking oral corticosteroids on a chronic, regular basis.
- Subjects using daytime oxygen therapy.
- Subjects who are currently pregnant (confirmed with positive pregnancy test) or breast feeding.
- History of respiratory tract infection (including the upper respiratory tract) and/or pulmonary exacerbation within 6 weeks prior to Screening (Visit 1).
- 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.
- History or current diagnosis of asthma and/or alpha 1 anti-trypsin deficiency.
- Known active tuberculosis.
- History of interstitial lung or massive pulmonary thromboembolic disease.
- History of bronchiectasis secondary to respiratory diseases other than COPD (eg, cystic fibrosis, Kartagener's syndrome, etc).
- 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.
- 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.
- Previous or current history of lung cancer.
- History of cancer (within 5 years prior to Visit 1), except for non-metastatic, non melanoma skin cancer.
- Subjects who cannot perform spirometry manuevers or tolerate body plethysmography.
- Subjects with known hypersensitivity to Symbicort, its monocomponents (budesonide or formoterol), or its excipients.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Research Site
Boston, Massachusetts, 02115
Research Site
Charlotte, North Carolina, 28207
Research Site
Hartford, Connecticut, 06105
Research Site
Philadelphia, Pennsylvania, 19140
Research Site
Spartanburg, South Carolina, 29303
About this study
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.
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.
Read the 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.
- Being tested
- Budesonide 160 mcg and formoterol fumarate dihydrate 4.5 mcg Inhalation aerosol, Matching Placebo pMDI 160/4.5 μg
- Keywords
- Respiratory, COPD, O2 Consumption
- Medical subject headings
- Pulmonary Disease, Chronic Obstructive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Budesonide 160 mcg and formoterol fumarate dihydrate 4.5 mcg Inhalation aerosolDrug
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
Matching Placebo pMDI 160/4.5 μgDrug
Placebo will be given according at the same dose and schedule as the active comparator - cross-over design.
| Study group | Role | What they receive |
|---|---|---|
| Symbicort pressurized Metered Dose Inhaler (pMDI) | Active comparator | Symbicort pressurized Metered Dose Inhaler (pMDI) Receives: Drug: Budesonide 160 mcg and formoterol fumarate dihydrate 4.5 mcg Inhalation aerosol |
| Placebo of reference drug | Placebo comparator | Placebo of reference drug Receives: Drug: Matching Placebo pMDI 160/4.5 μg |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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 (12)
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).
Measured: 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).
Measured: 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.
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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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).
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Aug 2015 (estimated)
- Study start25 Aug 2015
- Primary completion12 Aug 2016
- Study completion12 Aug 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (18)Papers the sponsor has linked to this study.
- Other trials for Chronic Obstructive Pulmonary Disease (COPD)Studies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 51 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02533505
- Sponsor's protocol ID
- D589CC00014
- Status last verified
- Jul 2018
- First submitted
- 30 Jul 2015
- Last updated
- 30 Jul 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Casaburi R, Kukafka D, Cooper CB, Witek TJ Jr, Kesten S. Improvement in exercise tolerance with the combination of tiotropium and pulmonary rehabilitation in patients with COPD. Chest. 2005 Mar;127(3):809-17. doi: 10.1378/chest.127.3.809.
PubMed 15764761Casanova C, Cote C, de Torres JP, Aguirre-Jaime A, Marin JM, Pinto-Plata V, Celli BR. Inspiratory-to-total lung capacity ratio predicts mortality in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2005 Mar 15;171(6):591-7. doi: 10.1164/rccm.200407-867OC. Epub 2004 Dec 10.
PubMed 15591470Diaz O, Villafranca C, Ghezzo H, Borzone G, Leiva A, Milic-Emili J, Lisboa C. Breathing pattern and gas exchange at peak exercise in COPD patients with and without tidal flow limitation at rest. Eur Respir J. 2001 Jun;17(6):1120-7. doi: 10.1183/09031936.01.00057801.
PubMed 11491153Di Marco F, Milic-Emili J, Boveri B, Carlucci P, Santus P, Casanova F, Cazzola M, Centanni S. Effect of inhaled bronchodilators on inspiratory capacity and dyspnoea at rest in COPD. Eur Respir J. 2003 Jan;21(1):86-94. doi: 10.1183/09031936.03.00020102.
PubMed 12570114Miller MR, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A, Crapo R, Enright P, van der Grinten CP, Gustafsson P, Jensen R, Johnson DC, MacIntyre N, McKay R, Navajas D, Pedersen OF, Pellegrino R, Viegi G, Wanger J; ATS/ERS Task Force. Standardisation of spirometry. Eur Respir J. 2005 Aug;26(2):319-38. doi: 10.1183/09031936.05.00034805. No abstract available.
PubMed 16055882O'Donnell DE, Lam M, Webb KA. Measurement of symptoms, lung hyperinflation, and endurance during exercise in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1998 Nov;158(5 Pt 1):1557-65. doi: 10.1164/ajrccm.158.5.9804004.
PubMed 9817708O'Donnell DE, Lam M, Webb KA. Spirometric correlates of improvement in exercise performance after anticholinergic therapy in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1999 Aug;160(2):542-9. doi: 10.1164/ajrccm.160.2.9901038.
PubMed 10430726O'Donnell DE, Revill SM, Webb KA. Dynamic hyperinflation and exercise intolerance in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2001 Sep 1;164(5):770-7. doi: 10.1164/ajrccm.164.5.2012122.
PubMed 11549531O'Donnell DE, D'Arsigny C, Fitzpatrick M, Webb KA. Exercise hypercapnia in advanced chronic obstructive pulmonary disease: the role of lung hyperinflation. Am J Respir Crit Care Med. 2002 Sep 1;166(5):663-8. doi: 10.1164/rccm.2201003.
PubMed 12204862Seibold H, Roth U, Lippert R, Kohler J, Wieshammer S, Henze E, Stauch M. Left heart function in chronic obstructive lung disease. Klin Wochenschr. 1986 May 2;64(9):433-41. doi: 10.1007/BF01727529.
PubMed 3713112Sexton WL, Poole DC. Effects of emphysema on diaphragm blood flow during exercise. J Appl Physiol (1985). 1998 Mar;84(3):971-9. doi: 10.1152/jappl.1998.84.3.971.
PubMed 9480959Sinderby C, Spahija J, Beck J, Kaminski D, Yan S, Comtois N, Sliwinski P. Diaphragm activation during exercise in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2001 Jun;163(7):1637-41. doi: 10.1164/ajrccm.163.7.2007033.
PubMed 11401887Stewart RI, Lewis CM. Cardiac output during exercise in patients with COPD. Chest. 1986 Feb;89(2):199-205. doi: 10.1378/chest.89.2.199.
PubMed 3943379Synn A, Pinto-Plata V, Perham C, Celli B, Divo M. Improvement in cost of breathing after use of budesonide/formoterol in COPD patients with static hyperinflation. Presented at The American Thoracic Society International Conference, May 16-21, 2014.
Vassaux C, Torre-Bouscoulet L, Zeineldine S, Cortopassi F, Paz-Diaz H, Celli BR, Pinto-Plata VM. Effects of hyperinflation on the oxygen pulse as a marker of cardiac performance in COPD. Eur Respir J. 2008 Nov;32(5):1275-82. doi: 10.1183/09031936.00151707. Epub 2008 Jun 11.
PubMed 18550609
Study at a glance
From the registry record, last updated by the sponsor on 30 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT02533505
- Acronym / sponsor ID
- D589CC00014
- Keywords
- Respiratory, COPD, O2 Consumption
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 51 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- 25 Aug 2015 (actual)
- Primary completion
- 12 Aug 2016 (actual)
- Study completion
- 12 Aug 2016 (actual)
- First posted
- 26 Aug 2015 (estimated)
- Results
- Posted 30 Jul 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Symbicort pressurized Metered Dose Inhaler (pMDI) | Active comparator | Drug: Budesonide 160 mcg and formoterol fumarate dihydrate 4.5 mcg Inhalation aerosolSymbicort pressurized Metered Dose Inhaler (pMDI) |
| Placebo of reference drug | Placebo comparator | Drug: Matching Placebo pMDI 160/4.5 μgPlacebo of reference drug |
Who may qualify
- Ages
- 40 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Signing of the informed consent form (ICF) prior to any study specific procedures, including withholding of medications.
- Male or female, aged 40 to 80 years, inclusive, at Screening (Visit 1).
- 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).
- 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.
- 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).
Key exclusion criteria (21 listed)
- 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).
- Previous enrollment or randomization in this study.
- Participation in another clinical study with an investigational product (IP) during the last 30 days prior to Screening (Visit 1).
- 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.
- Subjects who are taking uLABAs (indacaterol, vilanterol) or uLABA-containing products.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Budesonide 160 mcg and formoterol fumarate dihydrate 4.5 mcg Inhalation aerosolSubjects 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 | Drug | Symbicort pressurized Metered Dose Inhaler (pMDI) |
| Matching Placebo pMDI 160/4.5 μgPlacebo will be given according at the same dose and schedule as the active comparator - cross-over design. | Drug | Placebo of reference drug |
Primary outcome
Change From Pre-dose (Visit 2) to Post-dose (Visit 5) Assessment in Oxygen Consumption (VO2; Obtained Via a Metabolic Cart)
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.
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).
12 secondary outcomes
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)
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
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.
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
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
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
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
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
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
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
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
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.
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jul 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 15764761Casaburi R, Kukafka D, Cooper CB, Witek TJ Jr, Kesten S. Improvement in exercise tolerance with the combination of tiotropium and pulmonary rehabilitation in patients with COPD. Chest. 2005 Mar;127(3):809-17. doi: 10.1378/chest.127.3.809.
- Results publication: PubMed 15591470Casanova C, Cote C, de Torres JP, Aguirre-Jaime A, Marin JM, Pinto-Plata V, Celli BR. Inspiratory-to-total lung capacity ratio predicts mortality in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2005 Mar 15;171(6):591-7. doi: 10.1164/rccm.200407-867OC. Epub 2004 Dec 10.
- Results publication: PubMed 11491153Diaz O, Villafranca C, Ghezzo H, Borzone G, Leiva A, Milic-Emili J, Lisboa C. Breathing pattern and gas exchange at peak exercise in COPD patients with and without tidal flow limitation at rest. Eur Respir J. 2001 Jun;17(6):1120-7. doi: 10.1183/09031936.01.00057801.
- Results publication: PubMed 12570114Di Marco F, Milic-Emili J, Boveri B, Carlucci P, Santus P, Casanova F, Cazzola M, Centanni S. Effect of inhaled bronchodilators on inspiratory capacity and dyspnoea at rest in COPD. Eur Respir J. 2003 Jan;21(1):86-94. doi: 10.1183/09031936.03.00020102.
- Results publication: PubMed 16055882Miller MR, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A, Crapo R, Enright P, van der Grinten CP, Gustafsson P, Jensen R, Johnson DC, MacIntyre N, McKay R, Navajas D, Pedersen OF, Pellegrino R, Viegi G, Wanger J; ATS/ERS Task Force. Standardisation of spirometry. Eur Respir J. 2005 Aug;26(2):319-38. doi: 10.1183/09031936.05.00034805. No abstract available.
- Results publication: PubMed 9817708O'Donnell DE, Lam M, Webb KA. Measurement of symptoms, lung hyperinflation, and endurance during exercise in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1998 Nov;158(5 Pt 1):1557-65. doi: 10.1164/ajrccm.158.5.9804004.
- Results publication: PubMed 10430726O'Donnell DE, Lam M, Webb KA. Spirometric correlates of improvement in exercise performance after anticholinergic therapy in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1999 Aug;160(2):542-9. doi: 10.1164/ajrccm.160.2.9901038.
- Results publication: PubMed 11549531O'Donnell DE, Revill SM, Webb KA. Dynamic hyperinflation and exercise intolerance in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2001 Sep 1;164(5):770-7. doi: 10.1164/ajrccm.164.5.2012122.
- Results publication: PubMed 12204862O'Donnell DE, D'Arsigny C, Fitzpatrick M, Webb KA. Exercise hypercapnia in advanced chronic obstructive pulmonary disease: the role of lung hyperinflation. Am J Respir Crit Care Med. 2002 Sep 1;166(5):663-8. doi: 10.1164/rccm.2201003.
- Results publication: PubMed 3713112Seibold H, Roth U, Lippert R, Kohler J, Wieshammer S, Henze E, Stauch M. Left heart function in chronic obstructive lung disease. Klin Wochenschr. 1986 May 2;64(9):433-41. doi: 10.1007/BF01727529.
- Results publication: PubMed 9480959Sexton WL, Poole DC. Effects of emphysema on diaphragm blood flow during exercise. J Appl Physiol (1985). 1998 Mar;84(3):971-9. doi: 10.1152/jappl.1998.84.3.971.
- Results publication: PubMed 11401887Sinderby C, Spahija J, Beck J, Kaminski D, Yan S, Comtois N, Sliwinski P. Diaphragm activation during exercise in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2001 Jun;163(7):1637-41. doi: 10.1164/ajrccm.163.7.2007033.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Budesonide 160 mcg and formoterol fumarate dihydrate 4.5 mcg Inhalation aerosol in people with Chronic Obstructive Pulmonary Disease (COPD), run by AstraZeneca at 5 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 30 Jul 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Pre-dose (Visit 2) to Post-dose (Visit 5) Assessment in Oxygen Consumption (VO2; Obtained Via a Metabolic Cart) (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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02533505, which also lists 18 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jul 2018.