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Completed

NCT Number: NCT02634983

QVA Mechanistic Efficacy Study (Receptor Effects, Etc)

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.

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Key information

Conditions

Chronic Obstructive Pulmonary Disease Behavior Chronic Disease Disease Attributes Health Behavior Lung Diseases Lung Diseases, Obstructive Pathologic Processes Pathological Conditions, Signs and Symptoms Pulmonary Disease, Chronic Obstructive Respiratory Tract Diseases Smoking Cessation

Age range

40 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

Novartis Investigative Site, Sheffield, South Yorkshire, United Kingdom

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

QVA149

Drug

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

Drug

Matching placebo

Primary outcomes

  1. Global Ventilated Lung Volume

    Time frame: Day 8 to Day 10 (each treatment period)

    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 outcomes

  1. Regional Ventilated Lung Volume

    Time frame: Day 8 to Day 10 (each treatment period)

    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.

  2. Pulmonary Perfusion

    Time frame: Day 8 to Day 10 (each treatment period)

    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.

  3. Forced Expiratory Volume in 1 Second (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)

    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.

  4. Forced Vital Capacity (FVC)

    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)

    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.

  5. FEV1/FVC Ratio

    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)

    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%.

  6. Lung Clearance Index by Multiple Breath Nitrogen Washout (MBNW)

    Time frame: Day 8 (each treatment period)

    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).

  7. Diffusing Capacity of the Lung for Carbon Monoxide (DLCO)

    Time frame: Day 8 (each treatment period)

    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.

Sponsors and collaborators

Lead sponsor

Novartis Pharmaceuticals

Industry

Registry information

Official study 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

Important dates

Study start
2016
Primary completion
2017
Study completion
2017
First posted
Dec 18, 2015
Registry last updated
Jan 5, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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