QVA Mechanistic Efficacy Study (Receptor Effects, Etc)

Chronic Obstructive Pulmonary Disease Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02634983
• Other study ID #: CQVA149A2325
• Secondary ID: 2013-004461-13
• Status: Completed
• Phase: Phase 4
• Start date: June 3, 2016
• Est. completion date: September 26, 2017

Study information

• Verified date: February 2019
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 31
• Est. completion date: September 26, 2017
• Est. primary completion date: September 26, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Chronic Obstructive Pulmonary Disease
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• QVA149
QVA149 110/50 µg o.d. capsules for inhalation, supplied in blisters via the Concept 1 inhalation device, a single dose dry powder inhaler.
• Placebo
Matching placebo

Locations

Country	Name	City	State
United Kingdom	Novartis Investigative Site	Bradford	West Yorkshire
United Kingdom	Novartis Investigative Site	Manchester
United Kingdom	Novartis Investigative Site	Sheffield	South Yorkshire

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Day 8 to Day 10 (each treatment period)
Secondary	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.	Day 8 to Day 10 (each treatment period)
Secondary	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.	Day 8 to Day 10 (each treatment period)
Secondary	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.	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)
Secondary	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.	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)
Secondary	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%.	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)
Secondary	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).	Day 8 (each treatment period)
Secondary	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.	Day 8 (each treatment period)

External Links

•   A Plain Language Trial Summary is available on novartisclinicatrials.com