Phase IV O2 Consumption Study in COPD Patients.

NCT02533505 | Completed Phase 4 Results

• 1 other identifier: D589CC00014
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 5

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.

Conditions

Chronic Obstructive Pulmonary Disease (COPD)

Keywords

Respiratory; COPD; O2 Consumption

Outcome Measures

Primary Outcomes (1)

• 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 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)

  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

  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.

  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

  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

  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.

Study Arms (2)

Symbicort pressurized Metered Dose Inhaler (pMDI)

ACTIVE COMPARATOR

Symbicort pressurized Metered Dose Inhaler (pMDI)

Drug: Budesonide 160 mcg and formoterol fumarate dihydrate 4.5 mcg Inhalation aerosol

Placebo of reference drug

PLACEBO COMPARATOR

Placebo of reference drug

Drug: Matching Placebo pMDI 160/4.5 μg

Interventions

Budesonide 160 mcg and formoterol fumarate dihydrate 4.5 mcg Inhalation aerosol DRUG

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

Symbicort pressurized Metered Dose Inhaler (pMDI)

Matching Placebo pMDI 160/4.5 μg DRUG

Placebo will be given according at the same dose and schedule as the active comparator - cross-over design.

Placebo of reference drug

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).
• 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).

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (5)

Research Site

Hartford, Connecticut, 06105, United States

Location

Research Site

Boston, Massachusetts, 02115, United States

Location

Research Site

Charlotte, North Carolina, 28207, United States

Location

Research Site

Philadelphia, Pennsylvania, 19140, United States

Location

Research Site

Spartanburg, South Carolina, 29303, United States

Location

Related Publications (18)

• 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.

  PMID: 15764761 RESULT

• Casanova 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.

  PMID: 15591470 RESULT

• Diaz 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.

  PMID: 11491153 RESULT

• Di 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.

  PMID: 12570114 RESULT

• Miller 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.

  PMID: 16055882 RESULT

• O'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.

  PMID: 9817708 RESULT

• O'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.

  PMID: 10430726 RESULT

• O'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.

  PMID: 11549531 RESULT

• O'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.

  PMID: 12204862 RESULT

• Seibold 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.

  PMID: 3713112 RESULT

• Sexton 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.

  PMID: 9480959 RESULT

• Sinderby 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.

  PMID: 11401887 RESULT

• Stewart 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.

  PMID: 3943379 RESULT

• Synn 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.

  RESULT

• 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.

  PMID: 18550609 RESULT

• Wanger J, Clausen JL, Coates A, Pedersen OF, Brusasco V, Burgos F, Casaburi R, Crapo R, Enright P, van der Grinten CP, Gustafsson P, Hankinson J, Jensen R, Johnson D, Macintyre N, McKay R, Miller MR, Navajas D, Pellegrino R, Viegi G. Standardisation of the measurement of lung volumes. Eur Respir J. 2005 Sep;26(3):511-22. doi: 10.1183/09031936.05.00035005. No abstract available.

  PMID: 16135736 RESULT

• Yan S, Kaminski D, Sliwinski P. Reliability of inspiratory capacity for estimating end-expiratory lung volume changes during exercise in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1997 Jul;156(1):55-9. doi: 10.1164/ajrccm.156.1.9608113.

  PMID: 9230726 RESULT

• Divo MJ, DePietro MR, Horton JR, Maguire CA, Celli BR. Metabolic and cardiorespiratory effects of decreasing lung hyperinflation with budesonide/formoterol in COPD: a randomized, double-crossover, placebo-controlled, multicenter trial. Respir Res. 2020 Jan 20;21(1):26. doi: 10.1186/s12931-020-1288-3.

  PMID: 31959167 DERIVED

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

Budesonide

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: AstraZeneca Clinical
• Organization: AstraZeneca

information.center@astrazeneca.com

1-877-240-9479

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 30, 2015
• First Posted: August 26, 2015
• Study Start: August 25, 2015
• Primary Completion: August 12, 2016
• Study Completion: August 12, 2016
• Last Updated: July 30, 2018
• Results First Posted: July 30, 2018

Record last verified: 2018-07

Locations

US (5)