Evaluation of the Efficacy and Safety of QVA149 (110/50 μg o.d.) vs Tiotropium (18 µg o.d.) + Salmeterol/Fluticasone Propionate FDC (50/500 µg b.i.d.) in Patients With Moderate to Severe COPD

Chronic Obstructive Pulmonary Disease (COPD) Clinical Trial

Official title:

A 26-week, Randomized, Double Blind, Parallel-group Multicenter Study to Assess the Efficacy and Safety of QVA149 (110/50 μg o.d.) vs Tiotropium (18 µg o.d.) + Salmeterol/Fluticasone Propionate FDC (50/500 µg b.i.d.) in Patients With Moderate to Severe COPD

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02603393
• Other study ID #: CQVA149A2316
• Secondary ID: 2015-000114-22
• Status: Completed
• Phase: Phase 4
• Start date: November 20, 2015
• Est. completion date: July 18, 2017

Study information

• Verified date: January 2019
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will evaluate the efficacy and safety of QVA149 (110/50 μg o.d.) vs tiotropium (18 µg o.d.) + salmeterol/fluticasone propionate FDC (50/500 µg b.i.d.) in patients with moderate to severe COPD

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1053
• Est. completion date: July 18, 2017
• Est. primary completion date: July 18, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years and older

Eligibility

Inclusion Criteria:

• Patients who have signed Informed Consent Form prior to initiation of any study-related procedure.

• Male and female adults aged = 40 years.

• Patients with moderate to severe airflow obstruction with stable COPD (Stage 2 or Stage 3) according to the 2014 GOLD Guidelines.

• Patients with a post-bronchodilator FEV1 =40 and < 80% of the predicted normal value, and post-bronchodilator FEV1/FVC < 0.70 at run-in Visit 101. (Post refers to 15 min after inhalation of 400 µg of salbutamol).

• Current or ex-smokers who have a smoking history of at least 10 pack years (e.g. 10 pack years = 1 pack /day x 10 years, or ½ pack/day x 20 years). An ex-smoker is defined as a patient who has not smoked for = 6 months at screening.

• Patients who are on triple treatment at least for the last 6 months (LAMA +LABA/ICS).

Exclusion Criteria:

• Patients who have not achieved acceptable spirometry results at Visit 101 in accordance with ATS (American Thoracic Society)/ERS (European Respiratory Society) criteria for acceptability (one retest may be performed for patients that don't meet the acceptability criteria) .

• Patients who have had more than one COPD exacerbation that required treatment with antibiotics and/or oral corticosteroids and/or hospitalization in the last year prior to Visit 1.

• Patients who developed a COPD exacerbation of any severity either 6 weeks before the screening (Visit 1) or between screening (Visit 1) and treatment (Visit 201) will not be eligible but will be permitted to be re-screened after a minimum of 6 weeks after the resolution of the COPD exacerbation.

Other protocol-defined inclusion/exclusion criteria may apply

Related Conditions & MeSH terms

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

Intervention

Drug:
• QVA149
QVA149 will be supplied in a capsule form in blister packs for use in the Novartis Concept 1 SDDPI
• Tiotropium
Tiotropium will be supplied as commercially available blisters, delivered via HandiHaler®
• Salmeterol/fluticasone
Salmeterol/fluticasone propionate dry inhalation powder delivered via Accuhaler™

Locations

Country	Name	City	State
Argentina	Novartis Investigative Site	Caba
Argentina	Novartis Investigative Site	Caba	Buenos Aires
Argentina	Novartis Investigative Site	Ciudad Autonoma de Bs As
Argentina	Novartis Investigative Site	Concepcion del Uruguay	Entre Rios
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	Quilmes	Buenos Aires
Argentina	Novartis Investigative Site	San Miguel de Tucuman	Tucuman
Argentina	Novartis Investigative Site	San Miguel de Tucuman	Tucuman
Austria	Novartis Investigative Site	Amstetten
Austria	Novartis Investigative Site	Feldbach
Austria	Novartis Investigative Site	Feldkirch
Austria	Novartis Investigative Site	Grieskirchen
Austria	Novartis Investigative Site	Thalheim bei Wels
Belgium	Novartis Investigative Site	Antwerpen
Belgium	Novartis Investigative Site	Eghezee
Belgium	Novartis Investigative Site	Erpent
Belgium	Novartis Investigative Site	Hasselt
Belgium	Novartis Investigative Site	Turnhout
Bulgaria	Novartis Investigative Site	Gabrovo
Bulgaria	Novartis Investigative Site	Ruse
Bulgaria	Novartis Investigative Site	Stara Zagora
Bulgaria	Novartis Investigative Site	Varna
Canada	Novartis Investigative Site	Burlington	Ontario
Canada	Novartis Investigative Site	Gatineau	Quebec
Canada	Novartis Investigative Site	Moncton	New Brunswick
Canada	Novartis Investigative Site	Quebec
Canada	Novartis Investigative Site	Quebec
Canada	Novartis Investigative Site	Quebec
Canada	Novartis Investigative Site	St-Charles-Borromée	Quebec
Canada	Novartis Investigative Site	Toronto	Ontario
Canada	Novartis Investigative Site	Toronto	Ontario
Canada	Novartis Investigative Site	Vancouver	British Columbia
Canada	Novartis Investigative Site	Victoriaville	Quebec
Croatia	Novartis Investigative Site	Rijeka	HRV
Croatia	Novartis Investigative Site	Zagreb
Czechia	Novartis Investigative Site	Benesov
Czechia	Novartis Investigative Site	Brandys nad Labem
Czechia	Novartis Investigative Site	Kyjov
Czechia	Novartis Investigative Site	Melnik	Czech Republic
Czechia	Novartis Investigative Site	Plzen
Denmark	Novartis Investigative Site	Copenhagen NV
Denmark	Novartis Investigative Site	Hvidovre
Estonia	Novartis Investigative Site	Kohtla-Jarve
Estonia	Novartis Investigative Site	Tallinn
Estonia	Novartis Investigative Site	Tallinn
Estonia	Novartis Investigative Site	Tartu
Germany	Novartis Investigative Site	Bad Woerishofen
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Bonn
Germany	Novartis Investigative Site	Cottbus	Sachsen
Germany	Novartis Investigative Site	Dresden
Germany	Novartis Investigative Site	Erlangen
Germany	Novartis Investigative Site	Frankfurt
Germany	Novartis Investigative Site	Frankfurt am Main
Germany	Novartis Investigative Site	Hagen
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Hannover	Niedersachsen
Germany	Novartis Investigative Site	Koblenz	Rheinland-Pfalz
Germany	Novartis Investigative Site	Leipzig
Germany	Novartis Investigative Site	Leipzig
Germany	Novartis Investigative Site	Leipzig
Germany	Novartis Investigative Site	Leipzig
Germany	Novartis Investigative Site	Lubeck
Germany	Novartis Investigative Site	Magdeburg
Germany	Novartis Investigative Site	Marburg
Germany	Novartis Investigative Site	Menden
Germany	Novartis Investigative Site	Neu Isenburg
Germany	Novartis Investigative Site	Oschatz
Germany	Novartis Investigative Site	Peine	Niedersachsen
Germany	Novartis Investigative Site	Potsdam
Germany	Novartis Investigative Site	Potsdam
Germany	Novartis Investigative Site	Rudersdorf
Germany	Novartis Investigative Site	Schleswig
Germany	Novartis Investigative Site	Solingen
Germany	Novartis Investigative Site	Warendorf	Nordrhein-Westfalen
Germany	Novartis Investigative Site	Wiesloch
Greece	Novartis Investigative Site	Athens
Greece	Novartis Investigative Site	Heraklion - Crete
Greece	Novartis Investigative Site	Thessaloniki	GR
Hungary	Novartis Investigative Site	Balassagyarmat
Hungary	Novartis Investigative Site	Budapest
Hungary	Novartis Investigative Site	Szazhalombatta	HUN
Hungary	Novartis Investigative Site	Szekszard
Hungary	Novartis Investigative Site	Torokbalint	Pest
Latvia	Novartis Investigative Site	Balvi	LVA
Latvia	Novartis Investigative Site	Daugavpils
Latvia	Novartis Investigative Site	Jurmala	LVA
Latvia	Novartis Investigative Site	Kraslava
Latvia	Novartis Investigative Site	Liepaja	LV
Latvia	Novartis Investigative Site	Riga	LV
Latvia	Novartis Investigative Site	Riga
Latvia	Novartis Investigative Site	Riga
Lithuania	Novartis Investigative Site	Kaunas	LT
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
Netherlands	Novartis Investigative Site	Alkmaar
Netherlands	Novartis Investigative Site	Breda
Netherlands	Novartis Investigative Site	Eindhoven
Netherlands	Novartis Investigative Site	Zutphen
Poland	Novartis Investigative Site	Bialystok
Poland	Novartis Investigative Site	Bialystok
Poland	Novartis Investigative Site	Bialystok
Poland	Novartis Investigative Site	Bienkowka
Poland	Novartis Investigative Site	Krakow
Poland	Novartis Investigative Site	Lodz
Poland	Novartis Investigative Site	Lublin
Poland	Novartis Investigative Site	Ostrów Wielkopolski
Poland	Novartis Investigative Site	Ostrowiec Swietokrzyskie	Swietokrzyskie
Poland	Novartis Investigative Site	Poznan
Poland	Novartis Investigative Site	Poznan
Poland	Novartis Investigative Site	Sopot
Poland	Novartis Investigative Site	Tarnow
Poland	Novartis Investigative Site	Wroclaw
Poland	Novartis Investigative Site	Wroclaw	Dolnoslaskie
Romania	Novartis Investigative Site	Arad
Romania	Novartis Investigative Site	Arad
Romania	Novartis Investigative Site	Brasov
Romania	Novartis Investigative Site	Bucharest
Romania	Novartis Investigative Site	Bucharest
Romania	Novartis Investigative Site	Bucuresti
Romania	Novartis Investigative Site	Bucuresti	District 1
Romania	Novartis Investigative Site	Cluj Napoca
Romania	Novartis Investigative Site	Deva
Romania	Novartis Investigative Site	Timisoara	Timis
Serbia	Novartis Investigative Site	Belgrade
Serbia	Novartis Investigative Site	Beograd
Serbia	Novartis Investigative Site	Knez Selo
Serbia	Novartis Investigative Site	Kragujevac
Serbia	Novartis Investigative Site	Valjevo
Slovakia	Novartis Investigative Site	Humenne
Slovakia	Novartis Investigative Site	Poprad
Slovakia	Novartis Investigative Site	Presov
Slovakia	Novartis Investigative Site	Spisska Nova Ves
Spain	Novartis Investigative Site	Alzira	Comunidad Valenciana
Spain	Novartis Investigative Site	Canet de Mar	Cataluna
Spain	Novartis Investigative Site	Centelles	Barcelona
Spain	Novartis Investigative Site	L´Hospitalet de Llobregat	Cataluña
Spain	Novartis Investigative Site	Malaga	Andalucia
Spain	Novartis Investigative Site	Merida	Extremadura
Spain	Novartis Investigative Site	Ponferrada	Castilla Y Leon
Spain	Novartis Investigative Site	San Juan de Alicante	Comunidad Valenciana
United Kingdom	Novartis Investigative Site	Bath
United Kingdom	Novartis Investigative Site	Birmingham
United Kingdom	Novartis Investigative Site	Birmingham
United Kingdom	Novartis Investigative Site	Bradford	West Yorkshire
United Kingdom	Novartis Investigative Site	Coventry
United Kingdom	Novartis Investigative Site	Crawley	West Sussex
United Kingdom	Novartis Investigative Site	Leamington Spa	Warwickshire
United Kingdom	Novartis Investigative Site	Plymouth
United Kingdom	Novartis Investigative Site	Wolverhampton

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

Argentina,  Austria,  Belgium,  Bulgaria,  Canada,  Croatia,  Czechia,  Denmark,  Estonia,  Germany,  Greece,  Hungary,  Latvia,  Lithuania,  Netherlands,  Poland,  Romania,  Serbia,  Slovakia,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean Change From Baseline in Post-dose Trough FEV1	Mean change from baseline in post-dose trough forced expiratory volume in 1 second (FEV1) following 26 weeks of treatment. Trough FEV1 is defined as the mean of the two FEV1 values measured at 23 hr 15 min and 23 hr 45 min after the morning dose taken at site on Day 181. Baseline FEV1 is defined as the average of the pre-dose FEV1 measured at -45 min and -15 min at Day 1.	Baseline, 26 weeks
Secondary	Annualized Rate of Moderate or Severe COPD Exacerbations	Moderate or severe COPD exacerbations starting between first dose and one day after last treatment are included. COPD exacerbations that occurred within 7 days of each other are collapsed as one event.	26 weeks
Secondary	Annualized Rate of COPD Exacerbations Requiring Treatment With Systemic Glucocorticosteroids and/or Antibiotics, Moderate Exacerbations Only	COPD exacerbations starting between first dose and one day after last treatment are included. COPD exacerbations that occurred within 7 days of each other are collapsed as one event	26 weeks
Secondary	Annualized Rate of COPD Exacerbations Requiring Hospitalisation	COPD exacerbations starting between first dose and one day after last treatment are included. COPD exacerbations that occurred within 7 days of each other are collapsed as one event.	26 weeks
Secondary	Mean Change From Baseline in Pre-dose Trough FEV1	Trough FEV1 is defined as the average of the pre-dose FEV1 measurements at -45 min and -15 min prior to dosing at each visit except Day 182 which is the average of the post-dose FEV1 measurements at 23h15min and 23h45min after dosing at Day 181. Baseline FEV1 is considered the Day 1 average of pre-dose measurements.	26 weeks
Secondary	Mean Change From Baseline in St. George's Respiratory Questionnaire	The St. George Respiratory Questionnaire C (SGRQ-C) is used to provide the health status measurements in this study. Baseline SGRQ-C is defined as the assessment taken right before the first dose of the double-blind drug on Day 1. Higher values correspond to greater impairment of health status. The SGRQ contains 50 items divided into 2 parts covering 3 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 was calculated for each of these 3 subscales and a "Total" score was calculated. In each case the lowest possible value is zero and the highest 100. Higher values correspond to greater impairment of health status.	Baseline, 12 weeks
Secondary	Mean Change From Baseline in St. George's Respiratory Questionnaire	The St. George Respiratory Questionnaire C (SGRQ-C) is used to provide the health status measurements in this study. Baseline SGRQ-C is defined as the assessment taken right before the first dose of the double-blind drug on Day 1. Higher values correspond to greater impairment of health status. The SGRQ contains 50 items divided into 2 parts covering 3 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 was calculated for each of these 3 subscales and a "Total" score was calculated. In each case the lowest possible value is zero and the highest 100. Higher values correspond to greater impairment of health status.	Baseline, 26 weeks
Secondary	Transition Dyspnea Index (TDI) Score	Transitional Dyspnea Index (TDI) score presents the degree of impairment due to dyspnea. The lower the score the worse the severity of dyspnea. The Baseline Dyspnea Index (BDI) / TDI is an instrument used to assess a participant's level of dyspnea. The BDI and TDI each have three domains: functional impairment, magnitude of task and magnitude of effort. BDI domains were rated from 0 (severe) to 4 (unimpaired) and rates summed for baseline focal score ranged from 0 to 12; lower scores mean worse severity. TDI domains were rated from -3 (major deterioration) to 3 (major improvement) and rates summed for transition focal score ranged from -9 to 9; negative scores indicate deterioration. A TDI focal score of =1 was defined as a clinically important improvement from baseline.	12 weeks
Secondary	Transition Dyspnea Index (TDI) Score	Transitional Dyspnea Index (TDI) score presents the degree of impairment due to dyspnea. The lower the score the worse the severity of dyspnea. The Baseline Dyspnea Index (BDI) / TDI is an instrument used to assess a participant's level of dyspnea. The BDI and TDI each have three domains: functional impairment, magnitude of task and magnitude of effort. BDI domains were rated from 0 (severe) to 4 (unimpaired) and rates summed for baseline focal score ranged from 0 to 12; lower scores mean worse severity. TDI domains were rated from -3 (major deterioration) to 3 (major improvement) and rates summed for transition focal score ranged from -9 to 9; negative scores indicate deterioration. A TDI focal score of =1 was defined as a clinically important improvement from baseline.	26 weeks
Secondary	Change From Baseline in the Mean Daily Number of Puffs of Rescue Medication	Change from baseline in mean daily number of puffs of rescue medication (number of puffs taken in the previous 12 hours) over 26 weeks of treatment.	Baseline, 26 weeks
Secondary	Mean Change From Baseline in Forced Vital Capacity (FVC)	Change from baseline in forced vital capacity following 26 weeks of treatment. Trough FVC is defined as the average of the pre-dose FVC measurements at -45 min and -15 min prior to dosing at each visit except Day 182 which is the average of the post-dose FVC measurements at 23h15min and 23h45min after dosing at Day 181. Baseline is considered the Day 1 average of pre-dose measurements.	Baseline, 26 weeks