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

Condition(s) targeted: Chronic Obstructive Pulmonary Disease

Intervention: QVA149 (Drug); Fluticasone/salmeterol (Drug); Placebo to QVA149 (Drug); Placebo to fluticasone/salmeterol (Drug)

Phase: Phase 3

Status: Completed

Sponsored by: Novartis Pharmaceuticals

Official(s) and/or principal investigator(s):
Novartis Pharmaceuticals, Study Director, Affiliation: Novartis Pharmaceuticals

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

Official title: A 26-week Treatment Randomized, Double-blind, Double Dummy, Parallel-group Study to Assess the Efficacy and Safety of QVA149 (Indacaterol / Glycopyrronium Bromide) Compared to Fluticasone/Salmeterol in Patients With Moderate to Severe COPD

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Primary outcome: 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

Secondary outcome:

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

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

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

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

Health Related Quality of Life Analysis of SGRQ Total Score After 26 Weeks of Treatment

Analysis of the TDI Focal Score Over the Whole Treatment Period

Rescue Medication Use: Summary of the Mean Daily, Daytime and Nighttime Number of Puffs of Rescue Medication, by 4 Weekly Intervals

Symptoms Reported Using E-diary Over 12 and 26 Weeks of Treatment

Detailed description: 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.

Minimum age: 40 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

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

Novartis Investigative Site, Buenos Aires C1125ABE, Argentina

Novartis Investigative Site, Cordoba X5016KEH, Argentina

Novartis Investigative Site, Santiago Piso 1, Chile

Novartis Investigative Site, Santiago, Chile

Novartis Investigative Site, Beijing, China

Novartis Investigative Site, Beijing 100029, China

Novartis Investigative Site, Beijing 100034, China

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Novartis Investigative Site, Beijing 100020, China

Novartis Investigative Site, Chongqing 400037, China

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Novartis Investigative Site, Chongqing 400042, China

Novartis Investigative Site, Jiangyin, China

Novartis Investigative Site, Nanjing, China

Novartis Investigative Site, Shanghai 200080, China

Novartis Investigative Site, Shanghai 200433, China

Novartis Investigative Site, Shanghai 200032, China

Novartis Investigative Site, Kaohsiung 81346, Taiwan

Novartis Investigative Site, Lin-Ko 33305, Taiwan

Novartis Investigative Site, Niaosong Township 83301, Taiwan

Novartis Investigative Site, Taichung 40705, Taiwan

Novartis Investigative Site, Taipei County, Taiwan

Novartis Investigative Site, Beijing, Beijing 100023, China

Novartis Investigative Site, Beijing, Beijing 100730, China

Novartis Investigative Site, Caba, Buenos Aires C1424BSF, Argentina

Novartis Investigative Site, Caba, Buenos Aires B8000XAV, Argentina

Novartis Investigative Site, Caba, Buenos Aires C1056ABJ, Argentina

Novartis Investigative Site, Caba, Buenos Aires C1280AEB, Argentina

Novartis Investigative Site, Caba, Buenos Aires C1425BEN, Argentina

Novartis Investigative Site, Caba, Buenos Aires 1122, Argentina

Novartis Investigative Site, La Plata, Buenos Aires 1900, Argentina

Novartis Investigative Site, Mar del Plata, Buenos Aires 7600, Argentina

Novartis Investigative Site, Rojas, Buenos Aires B2705XAE, Argentina

Novartis Investigative Site, Nanning, Guangxi 530021, China

Novartis Investigative Site, Shijiazhuang, Hebei 050000, China

Novartis Investigative Site, Wuhan, Hubei 430022, China

Novartis Investigative Site, Changsha City, Hunan 410011, China

Novartis Investigative Site, Changsha, Hunan 410003, China

Novartis Investigative Site, Nanjing, Jiangsu 210029, China

Novartis Investigative Site, Suzhou, Jiangsu 215004, China

Novartis Investigative Site, Nanchang, Jiangxi 330006, China

Novartis Investigative Site, Shengyang, Liaoning 110016, China

Novartis Investigative Site, Shenyang, Liaoning, China

Novartis Investigative Site, Santiago, Region Metropolitana, Chile

Novartis Investigative Site, Santiago, Region Metropolitana 8431633, Chile

Novartis Investigative Site, Qingdao, Shandong 266011, China

Novartis Investigative Site, Shanghai, Shanghai 200433, China

Novartis Investigative Site, Xi'an, Shanxi 710032, China

Novartis Investigative Site, Xi'an, Shanxi 710061, China

Novartis Investigative Site, Chengdu, Sichuan 610041, China

Novartis Investigative Site, Taipei, Taiwan, ROC 112, Taiwan

Novartis Investigative Site, San Miguel de Tucuman, Tucuman T4000IFL, Argentina

Novartis Investigative Site, Viña del Mar, Vina del Mar 2520024, Chile

Novartis Investigative Site, Hangzhou, Zhejiang 310003, China

Novartis Investigative Site, Hangzhou, Zhejiang 310006, China

Novartis Investigative Site, Hangzhou, Zhejiang 310016, China

Starting date: November 2012
Last updated: March 13, 2015