A 26-week Treatment Randomized, Double-blind, Double Dummy Study to Assess the Efficacy and Safety of QVA149

Novartis Pharmaceuticals744 enrolled

Overview

To demonstrate the non-inferiority of QVA149 110/50 µg o.d. to fluticasone/salmeterol 500/50 µg b.i.d. in terms of trough Forced Expiratory Volume in one second (FEV1) (mean of 23 hours 15 min and 23 hours 45 min post QVA149 dose) following 26 weeks of treatment in patients with moderate to severe COPD. The study population will consist of approximate 736 male and female adults (age 40 years and greater) with a clinical diagnosis of stable COPD \[GOLD (2010)\] and a smoking history of at least 10 pack years. It is anticipated that approximately 981 patients will need to be screened in order to randomize 736 patients into 2 treatment arms of the study with an equal randomization ratio, meaning QVA149 (368 patients), fluticasone/salmeterol (368 patients). Treatment randomization will be stratified by current/ex-smoker status and prior ICS use. It is intended that 552 patients will complete the study at Week 26 without major protocol deviations. Dropouts will not be replaced. This will be a multi-national study, including China, and at least two other countries. Standardization FEV1 AUC0-12h will be performed in a subgroup of around 100 patients (50 patients per treatment arm) in pre-selected centers.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

744

Conditions

Chronic Obstructive Pulmonary Disease

Interventions

QVA149DRUG

QVA149 110/50 µg capsules q.d. for inhalation, delivered via Novartis single dose dry powder inhaler (SDDPI).

Fluticasone/salmeterolDRUG

Active fluticasone/salmeterol (500/50µg) b.i.d via a dry power inhaler Accuhaler® device.

Placebo to QVA149DRUG

Placebo to QVA149 with SDDPI

Eligibility

Sex: ALLMin age: 40 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Patients with moderate to severe stable COPD (Stage II or Stage III) according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) Guideline. Current or ex-smokers who have a smoking history of at least 10 pack years. Patients with a post-bronchodilator Forced Expiratory Volume in one second (FEV1) ≥ 30% and \< 80% of the predicted normal, and post-bronchodilator FEV1/FVC \< 0.7. Modified Medical Research Council (mMRC) grade of at least 2 at Visit 2. Exclusion Criteria: * Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive Human Chorionic Gonadotropin (hCG) laboratory test. Patents with narrow-angle glaucoma, symptomatic benign prostatic hyperplasia (BPH), bladder-neck obstruction, moderate to severe renal impairment or urinary retention. BPH patients who are stable on treatment can be considered. Patients with a history of long QT syndrome or whose QTc measured at run-in (Visit 2) (Fridericia method) is prolonged (\>450 ms for males and females) as confirmed by the central Electrocardiogram (ECG) assessor. Patients with Type I or uncontrolled Type II diabetes. Patients who have not achieved spirometry result at Visit 2 in accordance with American Thoracic Society/European Respiratory Society (ATS/ERS) criteria for acceptability and repeatability. Patients with, a) any history of asthma or, b) onset of respiratory symptoms prior to age 40 years. Patients with concomitant pulmonary disease (e.g. lung fibrosis, primary bronchiectasis, sarcoidosis, interstitial lung disorder, pulmonary hypertension). Other protocol-defined inclusion/exclusion criteria may apply

Locations (55)

Outcomes

Primary Outcomes

Trough Forced Expiratory Volume in One Second (FEV1) Following 26 Weeks of Treatment to Demonstrate the Non-inferiority of QVA149 110/50 μg o.d. to Fluticasone/Salmeterol 500/50 μg b.i.d

Measurement of QVA149 110/50 μg o.d. to fluticasone/salmeterol 500/50 μg b.i.d. in terms of trough FEV1 (mean of 23 h 15 min and 23 h 45 min post QVA149 dose) following 26 weeks of treatment in patients with moderate to severe COPD.

Time frame: 26 weeks

Secondary Outcomes

Trough Forced Expiratory Volume in One Second (FEV1) Following 26 Weeks of Treatment to Demonstrate the Superiority of QVA 110/50μg o.d. to Fluticasone/Salmeterol 500/50 μg b.i.d

Time frame: 26 weeks

Standardized Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) 0-4 Hours

Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC) 0-4h at Day 1 was measured via spirometry conducted according to internationally accepted standards. Measurements were made at 0, 5, 15, and 30 minutes; and 1, 2, 3 and 4 hours post-dose. The standardized AUC FEV1 was calculated as the sum of trapezoids divided by the length of time. Mixed model used: AUC FEV1 = treatment + baseline FEV1 + FEV1 reversibility components + baseline smoking status + baseline ICS use + country + center (country) + error. Center was included as a random effect nested within country.

Time frame: Day 1, 12 and 26 weeks

Analysis of FEV1 (L) Trough Response (Pre-dose) Over the Whole Treatment Period

Average of Trough Forced Expiratory Volume in one second (FEV1)

Time frame: 6,12,18 and 26 weeks

Analysis of Trough FVC (L) Over the Whole Treatment Period

Average of Trough Forced Vital Capacity (FVC) at 23 hours 15 min and the 23 hours 45 min post dose

Time frame: 12 and 26 weeks

Data from ClinicalTrials.gov

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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

Caba, Buenos Aires, Argentina

Novartis Investigative Site

La Plata, Buenos Aires, Argentina

Novartis Investigative Site

Mar del Plata, Buenos Aires, Argentina

Novartis Investigative Site

Rojas, Buenos Aires, Argentina

...and 45 more locations