Clinical trial NCT01709903: A 26-week Treatment Randomized, Double-blind, Double Dummy Study to Assess the Efficacy and Safety of QVA149
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Obstructive Pulmonary Disease
Keywords: chronic obstructive pulmonary disease
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2012-10-18
Enrollment: 744
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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

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.

Eligibility 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

Primary outcomes:
measure: 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
timeFrame: 26 weeks
Secondary outcomes:
measure: 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
timeFrame: 26 weeks
measure: Standardized Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) 0-4 Hours
timeFrame: Day 1, 12 and 26 weeks
measure: Analysis of FEV1 (L) Trough Response (Pre-dose) Over the Whole Treatment Period
timeFrame: 6,12,18 and 26 weeks
measure: Analysis of Trough FVC (L) Over the Whole Treatment Period
timeFrame: 12 and 26 weeks
measure: Health Related Quality of Life Analysis of SGRQ Total Score After 26 Weeks of Treatment
timeFrame: 26 weeks
measure: Analysis of the TDI Focal Score Over the Whole Treatment Period
timeFrame: 12 and 26 weeks
measure: Rescue Medication Use: Summary of the Mean Daily, Daytime and Nighttime Number of Puffs of Rescue Medication, by 4 Weekly Intervals
timeFrame: 12 and 26 weeks
measure: Symptoms Reported Using E-diary Over 12 and 26 Weeks of Treatment
timeFrame: 26 weeks
Other outcomes:
Locations:
city: Caba
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Caba
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Caba
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Caba
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Caba
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Caba
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: La Plata
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Mar del Plata
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Rojas
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: San Miguel de Tucuman
country: Argentina
facility: Novartis Investigative Site
state: Tucuman
city: Buenos Aires
country: Argentina
facility: Novartis Investigative Site
city: Cordoba
country: Argentina
facility: Novartis Investigative Site
city: Santiago
country: Chile
facility: Novartis Investigative Site
state: Region Metropolitana
city: Santiago
country: Chile
facility: Novartis Investigative Site
state: Region Metropolitana
city: Viña del Mar
country: Chile
facility: Novartis Investigative Site
state: Vina del Mar
city: Santiago
country: Chile
facility: Novartis Investigative Site
city: Santiago
country: Chile
facility: Novartis Investigative Site
city: Beijing
country: China
facility: Novartis Investigative Site
state: Beijing
city: Beijing
country: China
facility: Novartis Investigative Site
state: Beijing
city: Nanning
country: China
facility: Novartis Investigative Site
state: Guangxi
city: Shijiazhuang
country: China
facility: Novartis Investigative Site
state: Hebei
city: Wuhan
country: China
facility: Novartis Investigative Site
state: Hubei
city: Changsha City
country: China
facility: Novartis Investigative Site
state: Hunan
city: Changsha
country: China
facility: Novartis Investigative Site
state: Hunan
city: Nanjing
country: China
facility: Novartis Investigative Site
state: Jiangsu
city: Suzhou
country: China
facility: Novartis Investigative Site
state: Jiangsu
city: Nanchang
country: China
facility: Novartis Investigative Site
state: Jiangxi
city: Shengyang
country: China
facility: Novartis Investigative Site
state: Liaoning
city: Shenyang
country: China
facility: Novartis Investigative Site
state: Liaoning
city: Qingdao
country: China
facility: Novartis Investigative Site
state: Shandong
city: Shanghai
country: China
facility: Novartis Investigative Site
state: Shanghai
city: Xi'an
country: China
facility: Novartis Investigative Site
state: Shanxi
city: Xi'an
country: China
facility: Novartis Investigative Site
state: Shanxi
city: Chengdu
country: China
facility: Novartis Investigative Site
state: Sichuan
city: Hangzhou
country: China
facility: Novartis Investigative Site
state: Zhejiang
city: Hangzhou
country: China
facility: Novartis Investigative Site
state: Zhejiang
city: Hangzhou
country: China
facility: Novartis Investigative Site
state: Zhejiang
city: Beijing
country: China
facility: Novartis Investigative Site
city: Beijing
country: China
facility: Novartis Investigative Site
city: Beijing
country: China
facility: Novartis Investigative Site
city: Beijing
country: China
facility: Novartis Investigative Site
city: Beijing
country: China
facility: Novartis Investigative Site
city: Chongqing
country: China
facility: Novartis Investigative Site
city: Chongqing
country: China
facility: Novartis Investigative Site
city: Chongqing
country: China
facility: Novartis Investigative Site
city: Jiangyin
country: China
facility: Novartis Investigative Site
city: Nanjing
country: China
facility: Novartis Investigative Site
city: Shanghai
country: China
facility: Novartis Investigative Site
city: Shanghai
country: China
facility: Novartis Investigative Site
city: Shanghai
country: China
facility: Novartis Investigative Site
city: Taipei
country: Taiwan
facility: Novartis Investigative Site
state: Taiwan, ROC
city: Kaohsiung
country: Taiwan
facility: Novartis Investigative Site
city: Lin-Ko
country: Taiwan
facility: Novartis Investigative Site
city: Niaosong Township
country: Taiwan
facility: Novartis Investigative Site
city: Taichung
country: Taiwan
facility: Novartis Investigative Site
city: Taipei County
country: Taiwan
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: Zhong N, Wang C, Zhou X, Zhang N, Humphries M, Wang L, Patalano F, Banerji D. Efficacy and Safety of Indacaterol/Glycopyrronium (IND/GLY) Versus Salmeterol/Fluticasone in Chinese Patients with Moderate-to-Severe Chronic Obstructive Pulmonary Disease: The Chinese Cohort from the LANTERN Study. COPD. 2016 Dec;13(6):686-692. doi: 10.1080/15412555.2016.1182970. Epub 2016 Aug 11.
citation: Zhong N, Wang C, Zhou X, Zhang N, Humphries M, Wang L, Thach C, Patalano F, Banerji D; LANTERN Investigators. LANTERN: a randomized study of QVA149 versus salmeterol/fluticasone combination in patients with COPD. Int J Chron Obstruct Pulmon Dis. 2015 Jun 5;10:1015-26. doi: 10.2147/COPD.S84436. eCollection 2015.