Comparison of Long-term Safety of the Combination Product QVA149A Against Placebo and Standard of Care Treatment in Chronic Obstructive Pulmonary Disease Patients With Moderate to Severe Airflow Limitation

Novartis Pharmaceuticals1,215 enrolled

Overview

The study will assess the long-term safety of the fixed combination product QVA149 versus placebo and a standard of care treatment (tiotropium) in Chronic Obstructive Pulmonary Disease (COPD) patients with moderate to severe airflow limitation.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

1,215

Conditions

Chronic Obstructive Pulmonary Disease (COPD)

Interventions

QVA149DRUG

QVA149 110/50 µg will be supplied as capsules in blister packs for once daily inhalation using the Novartis Concept1 SDDPI

TiotropiumDRUG

Tiotropium 18 µg will be supplied as capsules in blister packs for once daily inhalation using the HandiHaler SDDPI

placeboDRUG

placebo to QVA149A and Tiotropium will be supplied in the appropriate capsule in blister packs for use in either the Novartis Concept1 SDDPI or the HandiHaler SDDPI

Eligibility

Sex: ALLMin age: 40 Years

Medical Language ↔ Plain English

Inclusion criteria: * Male and female adults aged ≥40 years. * Patients with stable COPD according to GOLD strategy (GOLD 2011). * Patients with airflow limitation indicated by a post-bronchodilator FEV1 ≥ 30% and \<80% of the predicted normal, and a post-bronchodilator. * FEV1/FVC \< 0.70. * Current or ex-smokers who have a smoking history of at least 10 pack years. * Patients with an mMRC ≥ grade 2 Exclusion criteria: * History of long QT syndrome or prolonged QTc. * Patients who have had a COPD exacerbation that required treatment with antibiotics and/or systemic corticosteroids and/or hospitalization in the 6 weeks prior to Visit 1. * Patients with Type I or uncontrolled Type II diabetes. * Patients with a history of asthma or have concomitant pulmonary disease. * Patients with paroxysmal (e.g. intermittent) atrial fibrillation. Only patients with persistent atrial fibrillation and controlled with a rate control strategy for at least six months could be eligible. * Patients who have clinically significant renal, cardiovascular, neurological, endocrine, immunological, psychiatric, gastrointestinal, hepatic, or hematological abnormalities which could interfere with the assessment of safety.

Locations (116)

Outcomes

Primary Outcomes

Number of Patients With Serious Adverse Events

The overall rate of serious adverse events reported from initiation through 30 days post last dose.

Time frame: Week 52

Secondary Outcomes

Percentage of Patients With Composite Endpoint of All-cause Mortality, and Serious Cardio- and Cerebrovascular (CCV) Events.

The endpoint of all-cause mortality and serious CCV events (composite) was chosen to further characterize any discernible risks. The patients with an event in the analysis were those who had at least one of the 2 events namely, all-cause mortality and serious CCV, during treatment or within 30 days after the date of last dose of study drug.

Time frame: 52 weeks

Post-hoc Analysis: Percentage of Patients With Composite Endpoint of Cardiovascular Death and MACE

The composite endpoint included all deaths and all serious CCV events, including MACE and events which were not considered MACE. A rigorous post hoc analysis was done on composite endpoint of CV deaths and major adverse cardiovascular events (MACE). The patients with an event in the analysis were those who had at least one of the 2 events namely, CV deaths and MACE, during treatment or within 30 days after the date of last dose of study drug.

Time frame: 52 weeks

Change From Baseline in Pre-Dose Forced Expiratory Volume Over in Second (FEV1)

Pulmonary function assessments were performed using centralized spirometry according to international standards. Baseline FEV1 was defined as the average of the pre-dose FEV1 measured at -45 minutes (min) and -15 min at day 1.

Time frame: Day 22, 43, 85, 183, 274 and 364

Change From Baseline in Health Status as Measured by St. George's Respiratory Questionnaire for COPD Patients (SGRQ-C)

The SGRQ-C contains 40 items divided into two parts covering three aspects of health related to COPD: Part I covers "Symptoms" and is concerned with respiratory symptoms, their frequency and severity; Part II covers "Activity" and is concerned with activities that cause or are limited by breathlessness; Part II is also concerned with "Impacts" which covers a range of aspects concerned with social functioning and psychological disturbances resulting from airways disease. A score will be calculated for each of these three subscales and a "Total" score will also be calculated. In each case the lowest possible value is zero and the highest 100. Higher values correspond to greater impairment of health status.

Data from ClinicalTrials.gov

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Novartis Investigative Site

Buenos Aires, Buenos Aires, Argentina

Novartis Investigative Site

Buenos Aires, Buenos Aires, Argentina

Novartis Investigative Site

Caba, Buenos Aires, Argentina

Novartis Investigative Site

Caba, Buenos Aires, Argentina

Novartis Investigative Site

Caba, Buenos Aires, Argentina

Novartis Investigative Site

Caba, Buenos Aires, Argentina

Novartis Investigative Site

Caba, Buenos Aires, Argentina

Novartis Investigative Site

Florida, Buenos Aires, Argentina

Novartis Investigative Site

Lanús, Buenos Aires, Argentina

Novartis Investigative Site

Mar del Plata, Buenos Aires, Argentina

...and 106 more locations