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

Chronic Obstructive Pulmonary Disease (COPD) Clinical Trial

Official title:

A Placebo and Active Controlled Study to Assess the Long-term Safety of Once Daily QVA149 for 52 Weeks in Chronic Obstructive Pulmonary Disease (COPD) Patients With Moderate to Severe Airflow Limitation

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01610037
• Other study ID #: CQVA149A2339
• Secondary ID: 2012-002057-38
• Status: Recruiting
• Phase: Phase 3
• First received: May 30, 2012
• Last updated: October 21, 2014
• Start date: October 2012
• Est. completion date: January 2015

Study information

• Verified date: September 2014
• Source: Novartis
• Contact: Novartis Pharmaceuticals, 1862-778-8300
• Phone: +41613241111
• Is FDA regulated: No
• Health authority: Argentina: Administracion Nacional de Alimentos, Medicamentos y Tecnologia Medica (ANMAT)Croatia: Ministry of HealthDominican Republic: Consejo Nacional de Bioetica en Salud (CONABIOS)Estonia: State Agency of MedicineHungary: Directorate General of National Institute of Pharmacy/ National Institute for Quality and Organisational Development in Healthcare and MedicinesIndia: Drugs Controller General of IndiaIreland: Irish Medicines Board (IMB)Israel: Israeli Ministry of HealthSouth Korea: Korea Food and Drug Administration (KFDA)Latvia: State Agency of Medicines of LatviaMexico: Ministry of HealthPanama: Comite Nacional de Bioetica de la Investigacion con sede en Instituto Conmemorativo Gorgas de Estudios de la Salud (Ministry of Health)Poland: Ministry of HealthRussia: Ministry of Health of the Russian FederationSerbia: Medicines and Medical Devices Agency of SerbiaSlovenia: Public Agency of the Republic of Slovenia for Medicinal Products and Medical DevicesTurkey: Ministry of Health - Turkish Medicines and Medical Devices AgencyUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyVenezuela: Instituto Nacional de Higiene Rafael Rangel
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1224
• Est. completion date: January 2015
• Est. primary completion date: January 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years and older

Eligibility

Inclusion Criteria:

• Male or female adults aged =40 yrs

• Smoking history of at least 10 pack years

• Diagnosis of Chronic Obstructive Pulmonary Disease (COPD) (moderate to severe airflow limitation as classified by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) Guidelines, 2011)

• Post-bronchodilator Forced Expiratory Volume in 1 Second (FEV1)< 80% and = 30% of the predicted normal value and post-bronchodilator FEV1/FVC (forced vital capacity) <70%

• Modified Medical Research Council questionnaire grade of 2 or higher

Exclusion Criteria:

• Patients who have had a respiratory tract infection within 4 weeks prior to Visit 1

• Patients with concomitant pulmonary disease

• Patients with a history of asthma

• Any patient with lung cancer or a history of lung cancer

• Patients with a history of certain cardiovascular co-morbid conditions

• Patients with a known history and diagnosis of alpha-1 antitrypsin deficiency

• Patients in the active phase of a supervised pulmonary rehabilitation program

• Patients contraindicated for inhaled anticholinergic agents and ß2 agonists

• Other protocol-defined inclusion/exclusion criteria may apply

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Obstructive Pulmonary Disease (COPD)
• Lung Diseases
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• QVA149
QVA149 110/50 µg will be supplied as capsules in blister packs for once daily inhalation using the Novartis Concept1 SDDPI
• Tiotropium
Tiotropium 18 µg will be supplied as capsules in blister packs for once daily inhalation using the HandiHaler SDDPI
• placebo
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

Locations

Country	Name	City	State
Argentina	Novartis Investigative Site	Buenos Aires
Argentina	Novartis Investigative Site	Buenos Aires
Argentina	Novartis Investigative Site	Caba	Capital Federal
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	Caba	Buenos Aires
Argentina	Novartis Investigative Site	Concepcion del Uruguay	Entre Rios
Argentina	Novartis Investigative Site	Corrientes
Argentina	Novartis Investigative Site	Corrientes
Argentina	Novartis Investigative Site	Florencio Varela	Buenos Aires
Argentina	Novartis Investigative Site	Florida	Buenos Aires
Argentina	Novartis Investigative Site	La Plata	Buenos Aires
Argentina	Novartis Investigative Site	Lanus	Buenos Aires
Argentina	Novartis Investigative Site	Mar del Plata	Buenos Aires
Argentina	Novartis Investigative Site	Mar del Plata	Buenos Aires
Argentina	Novartis Investigative Site	Mendoza
Argentina	Novartis Investigative Site	Mendoza
Argentina	Novartis Investigative Site	Mendoza
Argentina	Novartis Investigative Site	Quilmes	Buenos Aires
Argentina	Novartis Investigative Site	Rosario	Santa Fe
Argentina	Novartis Investigative Site	Rosario	Santa Fe
Argentina	Novartis Investigative Site	Salta
Argentina	Novartis Investigative Site	San Isidro	Buenos Aires
Argentina	Novartis Investigative Site	San Miguel de Tucuman	Tucuman
Argentina	Novartis Investigative Site	Santa Fe	Rosario
Argentina	Novartis Investigative Site	Santa Fe
Argentina	Novartis Investigative Site	Santa Fe
Argentina	Novartis Investigative Site	Vicente Lopez	Buenos Aires
Colombia	Novartis Investigative Site	Armenia
Colombia	Novartis Investigative Site	Barranquilla
Colombia	Novartis Investigative Site	Bogota
Colombia	Novartis Investigative Site	Bogota
Colombia	Novartis Investigative Site	Bogota	Cundinamarca
Croatia	Novartis Investigative Site	Osijek
Croatia	Novartis Investigative Site	Sisak
Croatia	Novartis Investigative Site	Split
Croatia	Novartis Investigative Site	Zagreb
Croatia	Novartis Investigative Site	Zagreb
Dominican Republic	Novartis Investigative Site	Santo Domingo	Republica Dominicana
Estonia	Novartis Investigative Site	Tallinn
Estonia	Novartis Investigative Site	Tallinn
Estonia	Novartis Investigative Site	Tartu
Guatemala	Novartis Investigative Site	Guatemala City
Hungary	Novartis Investigative Site	Budapest
Hungary	Novartis Investigative Site	Cegled
Hungary	Novartis Investigative Site	Csorna
Hungary	Novartis Investigative Site	Debrecen
Hungary	Novartis Investigative Site	Eger
Hungary	Novartis Investigative Site	Erd
Hungary	Novartis Investigative Site	Godollo
Hungary	Novartis Investigative Site	Monor
Hungary	Novartis Investigative Site	Mosonmagyarovar
Hungary	Novartis Investigative Site	Siofok
Hungary	Novartis Investigative Site	Szarvas
India	Novartis Investigative Site	Ahmedabad
India	Novartis Investigative Site	Bangalore	Karnataka
India	Novartis Investigative Site	Bangalore	Karnataka
India	Novartis Investigative Site	Bikaner	Rajasthan
India	Novartis Investigative Site	Chennai	Tamil Nadu
India	Novartis Investigative Site	Coimbatore	Tamil Nadu
India	Novartis Investigative Site	Coimbatore	TN
India	Novartis Investigative Site	Hyderabad	A.p.
India	Novartis Investigative Site	Hyderabad	Andhra Pradesh
India	Novartis Investigative Site	Hyderabad	Andhra Pradesh
India	Novartis Investigative Site	Jaipur
India	Novartis Investigative Site	Jaipur	Rajasthan
India	Novartis Investigative Site	Jaipur	Rajasthan
India	Novartis Investigative Site	Mangalore	Karnataka
India	Novartis Investigative Site	Mysore	Karnataka
India	Novartis Investigative Site	Nagpur	Maharashtra
India	Novartis Investigative Site	Nagpur - Maharashtra
India	Novartis Investigative Site	Panjim
India	Novartis Investigative Site	Pune	Maharashtra
India	Novartis Investigative Site	Pune	Maharashtra
India	Novartis Investigative Site	Trivandrum	Kerala
India	Novartis Investigative Site	Vellore	Tamil Nadu
Ireland	Novartis Investigative Site	Cork
Ireland	Novartis Investigative Site	Dublin 24
Ireland	Novartis Investigative Site	Dublin 9
Ireland	Novartis Investigative Site	Galway
Israel	Novartis Investigative Site	Haifa
Israel	Novartis Investigative Site	Jerusalem
Israel	Novartis Investigative Site	Jerusalem
Israel	Novartis Investigative Site	Petach Tikva
Israel	Novartis Investigative Site	Rehovot
Korea, Republic of	Novartis Investigative Site	Bucheon-Si	Gyeonggi-Do
Korea, Republic of	Novartis Investigative Site	Daegu
Korea, Republic of	Novartis Investigative Site	Daegu
Korea, Republic of	Novartis Investigative Site	Incheon
Korea, Republic of	Novartis Investigative Site	Incheon
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul	Korea
Korea, Republic of	Novartis Investigative Site	Seoul	Korea
Latvia	Novartis Investigative Site	Daugavpils
Latvia	Novartis Investigative Site	Riga
Latvia	Novartis Investigative Site	Riga
Lithuania	Novartis Investigative Site	Alytus
Lithuania	Novartis Investigative Site	Klaipeda
Lithuania	Novartis Investigative Site	Klaipeda
Lithuania	Novartis Investigative Site	Utena
Lithuania	Novartis Investigative Site	Vilnius
Lithuania	Novartis Investigative Site	Vilnius
Lithuania	Novartis Investigative Site	Vilnius	LT
Mexico	Novartis Investigative Site	León	Guanajuato
Mexico	Novartis Investigative Site	Mexico	Distrito Federal
Mexico	Novartis Investigative Site	Mexico	Distrito Federal
Mexico	Novartis Investigative Site	México	Distrito Federal
Mexico	Novartis Investigative Site	Pachuca	Hidalgo
Panama	Novartis Investigative Site	Panama City	Panamá
Panama	Novartis Investigative Site	Panama City	Panamá
Panama	Novartis Investigative Site	Panama City	Panamá
Poland	Novartis Investigative Site	Bialystok
Poland	Novartis Investigative Site	Katowice
Poland	Novartis Investigative Site	Krakow
Poland	Novartis Investigative Site	Lodz
Poland	Novartis Investigative Site	Lodz
Russian Federation	Novartis Investigative Site	Moscow
Russian Federation	Novartis Investigative Site	Moscow
Russian Federation	Novartis Investigative Site	Moscow
Russian Federation	Novartis Investigative Site	Moscow
Russian Federation	Novartis Investigative Site	N.Novgorod
Russian Federation	Novartis Investigative Site	Nizhny Novgorod
Russian Federation	Novartis Investigative Site	Ryazan
Russian Federation	Novartis Investigative Site	Sankt-Peterburg
Russian Federation	Novartis Investigative Site	Saratov
Russian Federation	Novartis Investigative Site	St-Petersburg
Russian Federation	Novartis Investigative Site	St. Petersburg
Russian Federation	Novartis Investigative Site	St.-Petersburg
Russian Federation	Novartis Investigative Site	Yaroslavl
Serbia	Novartis Investigative Site	Knez Selo
Serbia	Novartis Investigative Site	Kragujevac
Slovenia	Novartis Investigative Site	Golnik
Turkey	Novartis Investigative Site	Istanbul
Turkey	Novartis Investigative Site	Kartal
Turkey	Novartis Investigative Site	Kocaeli
Turkey	Novartis Investigative Site	Mersin
Turkey	Novartis Investigative Site	Pendik / Istanbul
Turkey	Novartis Investigative Site	Yenisehir/Izmir
United Kingdom	Novartis Investigative Site	Birmingham
United Kingdom	Novartis Investigative Site	Birmingham
United Kingdom	Novartis Investigative Site	Bradford
United Kingdom	Novartis Investigative Site	Cheshire
United Kingdom	Novartis Investigative Site	Doncaster
United Kingdom	Novartis Investigative Site	East Sussex	Brighton
United Kingdom	Novartis Investigative Site	Leamington Spa	Warwickshire
United Kingdom	Novartis Investigative Site	Leeds
United Kingdom	Novartis Investigative Site	Merseyside
United Kingdom	Novartis Investigative Site	Newport
United Kingdom	Novartis Investigative Site	Portsmouth
United Kingdom	Novartis Investigative Site	Wolverhampton

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

Argentina,  Colombia,  Croatia,  Dominican Republic,  Estonia,  Guatemala,  Hungary,  India,  Ireland,  Israel,  Korea, Republic of,  Latvia,  Lithuania,  Mexico,  Panama,  Poland,  Russian Federation,  Serbia,  Slovenia,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	overall serious adverse event rate	The overall rate of serious adverse events reported from initiation through 30 days post last dose will be analyzed.	56 weeks	Yes
Secondary	Composite endpoint of all-cause mortality and serious cerebro-cardiovascular events	A composite endpoint of all-cause mortality and serious cerebro-cardiovascular events will be analyzed.	56 weeks	Yes
Secondary	Electrocardiogram	Data from the electrocardiograms will be summarized by treatment at all times.	weeks 1, 26 and 52	Yes
Secondary	Health Status as measured by St. George's Respiratory Questionnaire for COPD patients (SGRQ-C)	The St. George's Respiratory Questionnaire (SGRQ-C) will be used to provide the health status measurement. The SGRQ-C contains 40 items divided into two parts covering three aspects of health related to Chronic Obstructive Pulmonary Disease. A score will be calculated for each of these three parts 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.	52 weeks	No
Secondary	Daily, morning and evening symptom scores	Patients will be provided with an electronic diary (eDiary) to record daily clinical symptoms, or rescue medication. The patients will be instructed to routinely complete the patient diary twice daily. There are 9 total symptom questions for a total possible score of 27 at each timepoint. A higher score means the patient is reporting more symptoms related to Chronic Obstructive Pulmonary Disease.	52 weeks	No
Secondary	Percentage of nights with 'no nighttime awakenings'	A night with 'no nighttime awakenings' is defined from diary data as any night where the patient did not wake up due to symptoms. The percentage of nights with 'no nighttime awakenings' will be analyzed.	52 weeks	No
Secondary	Percentage of days with 'no daytime symptoms'	A day with 'no daytime symptoms' is defined from the diary data as any day where the patient has recorded in the evening no cough, no wheeze, no production of sputum and no feeling of breathlessness (other than when running) during the past 12 hours (approx 8 am to 8 pm). The percentage of days with 'no daytime symptoms' will be analyzed.	52 weeks	No
Secondary	Percentage of 'days able to perform usual daily activities'	A 'day able to perform usual daily activities' is defined from diary data as any day where the patient was not prevented from performing their usual daily activities due to respiratory symptoms. The percentage of 'days able to perform usual daily activities' will be analyzed.	52 weeks	No
Secondary	Pre-Dose forced expiratory volume over in second (FEV1)	The average pre-dose forced expiratory volume in 1 second (FEV1) at visit 4, 5, 6, 7, 8 and 9 will be analyzed.	Weeks 3, 6, 12, 26, 39, and 52	No
Secondary	Pre-Dose forced vital capacity (FVC)	The average pre-dose forced vital capacity (FVC) at visit 4, 5, 6, 7, 8 and 9 will be analyzed.	Weeks 3, 6, 12, 26, 39 and 52	No
Secondary	Post dose forced expiratory volume in one second (FEV1)	The avg 60 min post dose forced expiratory volume in 1 second (FEV1) at visit 4, 5, 6, 7, 8 and 9 will be analyzed.	Weeks 3, 6, 12, 26, 39, and 52	No
Secondary	Post Dose forced vital capacity (FVC)	The avg 60 min post dose forced vital capacity (FVC)at visit 4, 5, 6, 7, 8 and 9 will be analyzed.	Weeks 3, 6, 12, 26, 39, and 52	No
Secondary	Time to discontinuation	Time to premature discontinuation will be displayed graphically for each treatment group.	52 weeks	No
Secondary	Vital Signs	Vital signs (blood pressure and radial pulse rate) data will be summarized by treatment at pre-dose and 30 minute post-dose time points at Visits 3-9.	Weeks 3, 6, 12, 26, 39, and 52	Yes
Secondary	Lab values	All lab data will be listed with abnormal values flagged. The lab values and the change from baseline for continuous lab parameters will be summarized at each visit. A frequency table of results for categorical lab parameters will be produced by visit. Shift tables relative to normal ranges will be used to summarize the change from baseline to post-baseline by visit.	Weeks 6, 12, 26, 39, and 52	Yes