Clinical trial NCT02634983: 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
Overall status: COMPLETED
Phase: PHASE4
Conditions: Chronic Obstructive Pulmonary Disease
Keywords: COPD
Smokers
Ex-smokers
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2015-12-18
Enrollment: 31
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Global Ventilated Lung Volume
timeFrame: Day 8 to Day 10 (each treatment period)
Secondary outcomes:
measure: Regional Ventilated Lung Volume
timeFrame: Day 8 to Day 10 (each treatment period)
measure: Pulmonary Perfusion
timeFrame: Day 8 to Day 10 (each treatment period)
measure: Forced Expiratory Volume in 1 Second (FEV1)
timeFrame: 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)
measure: Forced Vital Capacity (FVC)
timeFrame: 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)
measure: FEV1/FVC Ratio
timeFrame: 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)
measure: Lung Clearance Index by Multiple Breath Nitrogen Washout (MBNW)
timeFrame: Day 8 (each treatment period)
measure: Diffusing Capacity of the Lung for Carbon Monoxide (DLCO)
timeFrame: Day 8 (each treatment period)
Other outcomes:
Locations:
city: Sheffield
country: United Kingdom
facility: Novartis Investigative Site
state: South Yorkshire
city: Bradford
country: United Kingdom
facility: Novartis Investigative Site
state: West Yorkshire
city: Manchester
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
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.