Back to resultsQVA Mechanistic Efficacy Study (Receptor Effects, Etc)
Primary Purpose
Chronic Obstructive Pulmonary Disease
Status
Completed
Phase
Phase 4
Locations
United Kingdom
Study Type
Interventional
Intervention
QVA149
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Obstructive Pulmonary Disease focused on measuring COPD, Smokers, Ex-smokers
Eligibility Criteria
Key Inclusion Criteria:
Males and females with COPD aged 40 years and above, weighing ≥45 kg and ≤100 kg, who were smokers and ex-smokers who had a smoking history of at least 10 pack years, and diagnosed with moderate to severe COPD according to GOLD 2015 criteria were included in the study. Patients with airflow limitation indicated by a post-bronchodilator FEV1/FVC < 0.70 and by a post-bronchodilator FEV1 ≥ 30 % and <80 % were included in the study. Post-bronchodilator refers to 1 hr (+/- 5 minutes) after sequential inhalation of 84 µg ipratropium bromide (or equivalent dose) and 400 µg salbutamol/360 µg albuterol (or equivalent dose).
Key Exclusion Criteria:
Patients with conditions which could compromise patient safety and compliance (as judged by the investigator), as well as conditions that required oxygen therapy for chronic hypoxemia, ≥25% emphysematous changes on a scan within 6 months to screening, those with lower respiratory infections within 6 weeks of screening, and patients with concomitant pulmonary disease were excluded from the study. Patients with asthma were also excluded from the study.
Pregnant or nursing (lactating) women, patients with poorly controlled Type I or Type II diabetes, patients with poor renal function, and those who were unable to use a dry powder inhaler or perform spirometry, and had contraindications to MRI were also excluded.
Sites / Locations
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
QVA149 110/50 mcg then Matching placebo
Matching placebo then QVA149 110/50 mcg
Arm Description
Single daily dose of 110/50 μg QVA149 for 8-10 days.
Single daily dose of matching placebo for 8-10 days.
Outcomes
Primary Outcome Measures
Global Ventilated Lung Volume
The global distribution of inhaled gas within the lung was assessed using an inhaled gaseous contrast agent, Hyperpolarized Helium (3He) Lung Imaging. The Global Ventilated Lung Volume was expressed in percentage (%VV) of total lung volume.
Secondary Outcome Measures
Regional Ventilated Lung Volume
The regional distribution of inhaled gas within the lung was assessed using an inhaled gaseous contrast agent, Hyperpolarized Helium (3He) Lung Imaging. The Regional Ventilated Lung Volume was expressed in percentage (% VDV) of total lung volume for each lobar region.
Pulmonary Perfusion
Lung Perfusion Imaging, or MR perfusion imaging of the lung with gadolinium contrast agent, was performed to determine whether vascular abnormalities producing perfusion deficits corresponded to abnormalities in ventilation (hypoxic vasoconstriction). Pulmonary Perfusion was expressed in ml/100 g lung tissue/min of each lobar region.
Forced Expiratory Volume in 1 Second (FEV1)
The Forced Expiratory Volume in one second (FEV1) was calculated as the volume of air forcibly exhaled in one second as measured by a spirometer.
Forced Vital Capacity (FVC)
Forced Vital Capacity (FVC) is the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. FVC was assessed via spirometry. An increase in FVC indicates improvement in lung function.
FEV1/FVC Ratio
The FEV1/FVC ratio is the proportion of a person's vital capacity that they are able to expire in the first second of forced expiration (FEV1) to the full, forced vital capacity (FVC). The result of this ratio is expressed as FEV1%.
Lung Clearance Index by Multiple Breath Nitrogen Washout (MBNW)
Multiple Breath Nitrogen Washout (MBNW) was performed after 2 hours post-dose spirometry assessments using a multiple breath inert gas washout technique. The device provides the global index of ventilation inhomogeneity assessment (LCI = Cumulative Expired Volume/Functional Residual Capacity).
Diffusing Capacity of the Lung for Carbon Monoxide (DLCO)
The diffusing capacity of the lung for carbon monoxide (DLCO) is a measure of how easily carbon monoxide (CO) molecules transfer from the alveolar gas to the hemoglobin of the red cells in the pulmonary circulation. To measure the DLCO, the patient inhales a single breath containing a minute amount of CO and holds it for 10 seconds. The breath is then exhaled and the exhaled breath is analyzed for CO. The change in the concentration of the CO is then multiplied by the single breath TLC to calculate the DLCO.
Full Information
NCT ID
NCT02634983
First Posted
October 28, 2015
Last Updated
December 9, 2020
Sponsor
Novartis Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT02634983
Brief Title
QVA Mechanistic Efficacy Study (Receptor Effects, Etc)
Official Title
A Randomized, Double-blind, Placebo-controlled, Two-period Crossover Study to Assess the Effect of Inhaled QVA149 on Global and Regional Lung Function and Gas Exchange in Patients With Moderate to Severe COPD
Study Type
Interventional
2. Study Status
Record Verification Date
February 2019
Overall Recruitment Status
Completed
Study Start Date
June 3, 2016 (Actual)
Primary Completion Date
September 26, 2017 (Actual)
Study Completion Date
September 26, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study was to assess global ventilated lung volume in moderate to severe COPD patients using MRI lung imaging after treatment with QVA149 compared to placebo.
Detailed Description
The MRI approach represented an opportunity to better understand the impact of a potent dual bronchodilator on the small and central airways and thereby increasing ventilated lung volume, gas exchange, and ventilation-perfusion deficits.
The study investigated the effect of QVA149 on global and regional lung ventilation using MRI lung imaging to enhance the understanding of QVA pharmacology in COPD patients.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Obstructive Pulmonary Disease
Keywords
COPD, Smokers, Ex-smokers
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
31 (Actual)
8. Arms, Groups, and Interventions
Arm Title
QVA149 110/50 mcg then Matching placebo
Arm Type
Experimental
Arm Description
Single daily dose of 110/50 μg QVA149 for 8-10 days.
Arm Title
Matching placebo then QVA149 110/50 mcg
Arm Type
Placebo Comparator
Arm Description
Single daily dose of matching placebo for 8-10 days.
Intervention Type
Drug
Intervention Name(s)
QVA149
Intervention Description
QVA149 110/50 μg o.d. capsules for inhalation, supplied in blisters via the Concept 1 inhalation device, a single dose dry powder inhaler.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Matching placebo
Primary Outcome Measure Information:
Title
Global Ventilated Lung Volume
Description
The global distribution of inhaled gas within the lung was assessed using an inhaled gaseous contrast agent, Hyperpolarized Helium (3He) Lung Imaging. The Global Ventilated Lung Volume was expressed in percentage (%VV) of total lung volume.
Time Frame
Day 8 to Day 10 (each treatment period)
Secondary Outcome Measure Information:
Title
Regional Ventilated Lung Volume
Description
The regional distribution of inhaled gas within the lung was assessed using an inhaled gaseous contrast agent, Hyperpolarized Helium (3He) Lung Imaging. The Regional Ventilated Lung Volume was expressed in percentage (% VDV) of total lung volume for each lobar region.
Time Frame
Day 8 to Day 10 (each treatment period)
Title
Pulmonary Perfusion
Description
Lung Perfusion Imaging, or MR perfusion imaging of the lung with gadolinium contrast agent, was performed to determine whether vascular abnormalities producing perfusion deficits corresponded to abnormalities in ventilation (hypoxic vasoconstriction). Pulmonary Perfusion was expressed in ml/100 g lung tissue/min of each lobar region.
Time Frame
Day 8 to Day 10 (each treatment period)
Title
Forced Expiratory Volume in 1 Second (FEV1)
Description
The Forced Expiratory Volume in one second (FEV1) was calculated as the volume of air forcibly exhaled in one second as measured by a spirometer.
Time Frame
Day 1 (0.25, 1 and 2 hours post-dose), Day 8 (-0.75, -0.25, 0.25, 1 and 2 hours post-dose) (each treatment period)
Title
Forced Vital Capacity (FVC)
Description
Forced Vital Capacity (FVC) is the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. FVC was assessed via spirometry. An increase in FVC indicates improvement in lung function.
Time Frame
Day 1 (0.25, 1 and 2 hours post-dose), Day 8 (-0.75, -0.25, 0.25, 1 and 2 hours post-dose) (each treatment period)
Title
FEV1/FVC Ratio
Description
The FEV1/FVC ratio is the proportion of a person's vital capacity that they are able to expire in the first second of forced expiration (FEV1) to the full, forced vital capacity (FVC). The result of this ratio is expressed as FEV1%.
Time Frame
Day 1 (0.25, 1 and 2 hours post-dose), Day 8 (-0.75, -0.25, 0.25, 1 and 2 hours post-dose) (each treatment period)
Title
Lung Clearance Index by Multiple Breath Nitrogen Washout (MBNW)
Description
Multiple Breath Nitrogen Washout (MBNW) was performed after 2 hours post-dose spirometry assessments using a multiple breath inert gas washout technique. The device provides the global index of ventilation inhomogeneity assessment (LCI = Cumulative Expired Volume/Functional Residual Capacity).
Time Frame
Day 8 (each treatment period)
Title
Diffusing Capacity of the Lung for Carbon Monoxide (DLCO)
Description
The diffusing capacity of the lung for carbon monoxide (DLCO) is a measure of how easily carbon monoxide (CO) molecules transfer from the alveolar gas to the hemoglobin of the red cells in the pulmonary circulation. To measure the DLCO, the patient inhales a single breath containing a minute amount of CO and holds it for 10 seconds. The breath is then exhaled and the exhaled breath is analyzed for CO. The change in the concentration of the CO is then multiplied by the single breath TLC to calculate the DLCO.
Time Frame
Day 8 (each treatment period)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria:
Males and females with COPD aged 40 years and above, weighing ≥45 kg and ≤100 kg, who were smokers and ex-smokers who had a smoking history of at least 10 pack years, and diagnosed with moderate to severe COPD according to GOLD 2015 criteria were included in the study. Patients with airflow limitation indicated by a post-bronchodilator FEV1/FVC < 0.70 and by a post-bronchodilator FEV1 ≥ 30 % and <80 % were included in the study. Post-bronchodilator refers to 1 hr (+/- 5 minutes) after sequential inhalation of 84 µg ipratropium bromide (or equivalent dose) and 400 µg salbutamol/360 µg albuterol (or equivalent dose).
Key Exclusion Criteria:
Patients with conditions which could compromise patient safety and compliance (as judged by the investigator), as well as conditions that required oxygen therapy for chronic hypoxemia, ≥25% emphysematous changes on a scan within 6 months to screening, those with lower respiratory infections within 6 weeks of screening, and patients with concomitant pulmonary disease were excluded from the study. Patients with asthma were also excluded from the study.
Pregnant or nursing (lactating) women, patients with poorly controlled Type I or Type II diabetes, patients with poor renal function, and those who were unable to use a dry powder inhaler or perform spirometry, and had contraindications to MRI were also excluded.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Novartis Investigative Site
City
Sheffield
State/Province
South Yorkshire
ZIP/Postal Code
S10 2JF
Country
United Kingdom
Facility Name
Novartis Investigative Site
City
Bradford
State/Province
West Yorkshire
ZIP/Postal Code
BD9 6RJ
Country
United Kingdom
Facility Name
Novartis Investigative Site
City
Manchester
ZIP/Postal Code
M23 9QZ
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
35144620
Citation
Singh D, Wild JM, Saralaya D, Lawson R, Marshall H, Goldin J, Brown MS, Kostikas K, Belmore K, Fogel R, Patalano F, Drollmann A, Machineni S, Jones I, Yates D, Tillmann HC. Effect of indacaterol/glycopyrronium on ventilation and perfusion in COPD: a randomized trial. Respir Res. 2022 Feb 10;23(1):26. doi: 10.1186/s12931-022-01949-3.
Results Reference
derived
Links:
URL
https://www.novctrd.com/ctrdweb/patientsummary/patientsummaries?patientSummaryId=364
Description
A Plain Language Trial Summary is available on novartisclinicatrials.com
Learn more about this trial
QVA Mechanistic Efficacy Study (Receptor Effects, Etc)
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