A Study to Compare the Lung Effect of Indacaterol and Tiotropium in Chronic Obstructive Pulmonary Disease (COPD)

Chronic Obstructive Pulmonary Disease Clinical Trial

— INTENSITY  

Official title:

A 12-week Treatment, Multicenter, Randomized, Parallel-group, Blinded, Double-dummy Study to Compare the Efficacy and Safety of Indacaterol (150 µg Once Daily [od]) Delivered Via a Single Dose Dry Powder Inhaler (SDDPI) With Tiotropium (18 µg od) Delivered Via a HandiHaler®, in Patients With Moderate-to-severe COPD

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00900731
• Other study ID #: CQAB149B2350
• Status: Completed
• Phase: Phase 3
• First received: May 12, 2009
• Last updated: July 22, 2011
• Start date: June 2009
• Est. completion date: March 2010

Study information

• Verified date: July 2011
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationSlovakia: State Institute for Drug ControlBelgium: Federal Agency for Medicinal Products and Health ProductsNorway: Norwegian Medicines AgencySwitzerland: EthikkommissionUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyAustria: Federal Office for Safety in Health CareColombia: INVIMA Instituto Nacional de Vigilancia de Medicamentos y AlimentosFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Germany: Federal Institute for Drugs and Medical DevicesGreece: National Organization of MedicinesHungary: National Institute of PharmacyIsrael: Ethics CommissionMexico: Ministry of HealthPoland: Office for Registration of Medicinal Products, Medical Devices and Biocidal ProductsRussia: Ministry of Health of the Russian FederationCanada: Health Canada
• Study type: Interventional

Clinical Trial Summary

This study compared the lung effects of indacaterol to those of tiotropium in patients with moderate to severe chronic obstructive pulmonary disease (COPD) over a 12 week period.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1598
• Est. completion date: March 2010
• Est. primary completion date: March 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years and older

Eligibility

Inclusion Criteria:

• Diagnosis of COPD (moderate-to-severe as classified by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) Guidelines, 2007) and:

• a) Smoking history of at least 10 pack-years

• b) Post-bronchodilator forced expiratory volume in 1 second (FEV1) < 80% and = 30% of the predicted normal value

• c) Post-bronchodilator FEV1/FVC (forced vital capacity) < 70%

Exclusion Criteria:

• Patients who have received systemic corticosteroids or antibiotics and/or was hospitalized for a COPD exacerbation in the 6 weeks prior to screening

• Patients who have had a respiratory tract infection within 6 weeks prior to screening

• Patients with concomitant pulmonary disease

• Patients with a history of asthma

• Patients with diabetes Type I or uncontrolled diabetes Type II

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

• Patients with a history of certain cardiovascular comorbid conditions

Other protocol-defined inclusion/exclusion criteria applied to the study.

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Obstructive Pulmonary Disease
• Lung Diseases
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• Indacaterol 150 µg
Indacaterol 150 µg was provided in powder filled capsules with a single dose dry powder inhaler (SDDPI).
• Tiotropium 18 µg
Tiotropium 18 µg was provided in powder filled capsules with the manufacturer's proprietary inhalation device (HandiHaler®).
• Placebo to indacaterol
Placebo to indacaterol was provided in powder filled capsules with a single dose dry powder inhaler (SDDPI).
• Placebo to tiotropium
Placebo to tiotropium was provided in powder filled capsules with the manufacturer's proprietary inhalation device (HandiHaler®).

Locations

Country	Name	City	State
Austria	Novartis Investigator Site	Feldbach
Austria	Novartis Investigator Site	Gänserndorf
Austria	Novartis Investigator Site	Hallein
Belgium	Novartis Investigator Site	Bruxelles
Belgium	Novartis Investigator Site	Gilly
Belgium	Novartis Investigator Site	Jambes
Belgium	Novartis Investigator Site	Jette
Belgium	Novartis Investigator Site	Liège
Belgium	Novartis Investigator Site	Montigny-le-tilleul
Belgium	Novartis Investigator Site	Oostende
Belgium	Novartis Investigator Site	Saint Vith
Belgium	Novartis Investigator Site	Yvoir
Canada	Novartis Investigator Site	Calgary
Canada	Novartis Investigative Site	Mississauga
Canada	Novartis Investigative Site	Moncton
Canada	Novartis Investigative Site	New Market
Canada	Novartis Investigative SIte	Quebec
Canada	Novartis Investigative Site	St-Romuald
Canada	Novartis Investigative Site	Sudbury
Colombia	Novartis Investigator Site	Barranquilla
Colombia	Novartis Investigator Site	Bogota
Colombia	Novartis Investigator Site	Medellin
Denmark	Novartis Investigator Site	Aalborg
Denmark	Novartis Investigator Site	Frederiksberg
Denmark	Novartis Investigator Site	Næstved
Denmark	Novartis Investigator Site	Roskilde
Denmark	Novartis Investigator Site	Sønderborg
Denmark	Novartis Investigator Site	Vaerlose
Denmark	Novartis Investigator Site	Viborg
Finland	Novartis Investigator Site	Helsinki
Finland	Novartis Investigator Site	Jyväskylä
Finland	Novartis Investigator Site	Lahti
Finland	Novartis Investigator Site	OYS
Finland	Novartis Investigator Site	Pori
Finland	Novartis Investigator Site	Turku
France	Novartis Investigative Site	Ambroise
France	Novartis Investigative Site	Antibes
France	Novartis Investigator Site	Beuvry
France	Novartis Investigator Site	Ferolles-Attily
France	Novartis Investigative Site	Montpellier
France	Novartis Investigator Site	Nantes
France	Novartis Investigative Site	Nice
France	Novartis Investigative Site	Nimes
France	Novartis Investigative Site	Paris
France	Novartis Investigator Site	Paris
France	Novartis Investigative Site	Pessac
France	Novartis Investigator Site	Pierre Benite
France	Novartis Investigative Site	Suresnes
France	Novartis Investigator Site	Vandoeuvre Les Nancys
Germany	Novartis Investigator Site	Bergisch Gladbach
Germany	Novartis Investigator Site	Berlin
Germany	Novartis Investigator Site	Bochum
Germany	Novartis Investigator Site	Bonn
Germany	Novartis Investigator Site	Buchholz
Germany	Novartis Investigator Site	Coburg
Germany	Novartis Investigator Site	Dueren
Germany	Novartis Investigator Site	Eggenfelden
Germany	Novartis Investigator Site	Eschwege
Germany	Novartis Investigator Site	Euskirchen
Germany	Novartis Investigator Site	Freudenberg
Germany	Novartis Investigator Site	Fürth
Germany	Novartis Investigator Site	Gelsenkirchen
Germany	Novartis Investigator Site	Gummersbach
Germany	Novartis Investigator Site	Hagen
Germany	Novartis Investigator Site	Halle
Germany	Novartis Investigator Site	Hamburg
Germany	Novartis Investigator Site	Hannover
Germany	Novartis Investigator Site	Hoyerswerda
Germany	Novartis Investigator Site	Kassel
Germany	Novartis Investigative Site	Landsberg
Germany	Novartis Investigator Site	Leipzig
Germany	Novartis Investigator Site	Mainz
Germany	Novartis Investigator Site	Munich
Germany	Novartis Investigator Site	Oranienburg
Germany	Novartis Investigator Site	Radebeul
Germany	Novartis Investigator Site	Ratingen
Germany	Novartis Investigator Site	Ruhmannsfelden
Germany	Novartis Investigator Site	Rüsselsheim
Germany	Novartis Investigator Site	Solingen
Germany	Novartis Investigator Site	Stockach
Germany	Novartis Investigator Site	Teterow
Germany	Novartis Investigator Site	Vilshofen
Germany	Novartis Investigator Site	Wallerfing
Germany	Novartis Investigator Site	Wissen
Greece	Novartis Investigator Site	Athens
Hungary	Novartis Investigative Site	Budapest
Hungary	Novartis Investigator Site	Budapest
Hungary	Novartis Investigator Site	Debrecen
Hungary	Novartis Investigative Site	Farkasgyepu
Hungary	Novartis Investigative Site	Godollo
Hungary	Novartis Investigator Site	Szolnok
Israel	Novartis Investigator Site	Haifa
Israel	Novartis Investigator Site	Petach-Tikva
Italy	Novartis Investigator Site	Ancona
Italy	Novartis Investigator Site	Foggia
Italy	Novartis Investigative Site	Milano
Italy	Novartis Investigator Site	Milano
Italy	Novartis Investigative Site	Pavia
Italy	Novartis Investigator Site	Pavia
Italy	Novartis Investigative Site	Pisa
Italy	Novartis Investigator Site	Pisa
Mexico	Novartis Investigative Site	Huxquilucan
Mexico	Novartis Investigator Site	Mexico City
Mexico	Novartis Investigative Site	San Luis Potosi
Norway	Novartis Investigative Site	Ålesund
Norway	Novartis Investigator Site	Ålesund
Norway	Novartis Investigator Site	Drammen
Norway	Novartis Investigator Site	Follebu
Norway	Novartis Investigative Site	Kongsberg
Norway	Novartis Investigator Site	Kongsberg
Norway	Novartis Investigator Site	Kongsvinger
Norway	Novartis Investigator Site	Lierskogen
Norway	Novartis Investigative Site	Oslo
Norway	Novartis Investigator Site	Oslo
Norway	Novartis Investigator Site	Sandvika
Norway	Novartis Investigative Site	Skedsmokorset
Norway	Novartis Investigator Site	Stavanger
Norway	Novartis Investigative Site	Trondheim
Norway	Novartis Investigator Site	Trondheim
Poland	Novartis Investigator Site	Gdansk
Poland	Novartis Investigator Site	Katowice
Poland	Novartis Investigative Site	Krakow
Poland	Novartis Investigator Site	Krakow
Poland	Novartis Investigator Site	Piekary Slaskie
Poland	Novartis Investigator Site	Warszawa
Poland	Novartis Investigator Site	Wroclaw
Russian Federation	Novartis Investigator Site	Barnaul
Russian Federation	Novartis Investigator Site	Ekaterinburg
Russian Federation	Novartis Investigator Site	Kazan
Russian Federation	Novartis Investigator Site	Novosibirsk
Russian Federation	Novartis Investigator Site	Petrozavodsk
Russian Federation	Novartis Investigator Site	Ryazan
Russian Federation	Novartis Investigative Site	Saint-Petersburg
Russian Federation	Novartis Investigator Site	Saint-Petersburg
Russian Federation	Novartis Investigator Site	Samara
Slovakia	Novartis Investigator Site	Bratislava
Slovakia	Novartis Investigative Site	Kosice
Slovakia	Novartis Investigator Site	Kosice
Slovakia	Novartis Investigator Site	Kralovsky Chlmec
Slovakia	Novartis Investigator Site	Nitra
Slovakia	Novartis Investigative Site	Presov
Slovakia	Novartis Investigator Site	Zvolen
Spain	Novartis Investigative Site	Alcorcón
Spain	Novartis Investigator Site	Alicante
Spain	Novartis Investigator Site	Badalona
Spain	Novartis Investigative Site	Barcelona
Spain	Novartis Investigative Site	Begonte
Spain	Novartis Investigator Site	Burgos
Spain	Novartis Investigator Site	Caceres
Spain	Novartis Investigator Site	Canet de Mar
Spain	Novartis Investigative Site	Fuenlabrada
Spain	Novartis Investigative Site	Girona
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigator Site	Mataro
Spain	Novartis Investigator Site	Plasencia
Spain	Novartis Investigative Site	Ponferrada
Spain	Novartis Investigative Site	Pontevedra
Spain	Novartis Investigator Site	Prat de Llobregat
Spain	Novartis Investigative Site	Santander
Spain	Novartis Investigative Site	Valencia
Spain	Novartis Investigative Site	Vila-real
Switzerland	Novartis Investigator Site	Basel
Switzerland	Novartis Investigator Site	Bellinzona
Switzerland	Novartis Investigator Site	Lugano
Switzerland	Novartis Investigator Site	Muenchenstein
Switzerland	Novartis Investigative Site	Zuerich
Turkey	Novartis Investigator Site	Altunizade
Turkey	Novartis Investigator Site	Ankara
Turkey	Novartis Investigative Site	Aydin
Turkey	Novartis Investigator Site	Büyükçekmece / Ýstanbul
Turkey	Novartis Investigative Site	Fatih / Istanbul
Turkey	Novartis Investigator Site	Istanbul
Turkey	Novartis Investigator Site	Kahramanmaras
Turkey	Novartis Investigative Site	Mecidiyekoy/Istanbul
Turkey	Novartis Investigative Site	Mersin
Turkey	Novartis Investigative Site	Soke / Aydin
Turkey	Novartis Investigative Site	Yenisehir/Izmir
United Kingdom	Novartis Investigator Site	Ash Vale
United Kingdom	Novartis Investigator Site	Ashford
United Kingdom	Novartis Investigator Site	Bolton
United Kingdom	Novartis Investigator Site	Boscastle
United Kingdom	Novartis Investigator Site	Bradford
United Kingdom	Novartis Investigator Site	Chertsey
United Kingdom	Novartis Investigator Site	East Horsley
United Kingdom	Novartis Investigator Site	Newcastle-upon-Tyne
United Kingdom	Novartis Investigator Site	Plymouth
United Kingdom	Novartis Investigator Site	Watford
United States	Novartis Investigative Site	Albany	New York
United States	Novartis Investigator Site	Anaheim	California
United States	Novartis Investigative Site	Birmingham	Alabama
United States	Novartis Investigative Site	Charlotte	North Carolina
United States	Novartis Investigative Site	Columbus	Ohio
United States	Novartis Investigative Site	Evansville	Indiana
United States	Novartis Investigator Site	Fort Collins	Colorado
United States	Novartis Investigative Site	Henderson	Nevada
United States	Novartis Investigator Site	Jasper	Alabama
United States	Novartis Investigative Site	Lafayette	Louisiana
United States	Novartis Investigative Site	Larchmont	New York
United States	Novartis Investigative Site	Lincoln	Nebraska
United States	Novartis Investigative Site	New York	New York
United States	Novartis Investigator Site	Normal	Illinois
United States	Novartis Investigative Site	Phoenix	Arizona
United States	Novartis Investigative Site	Richmond	Virginia
United States	Novartis Investigative Site	San Antonio	Texas
United States	Novartis Investigative Site	South Miami	Florida
United States	Novartis Investigative Center	St Charles	Missouri
United States	Novartis Investigative Site	St Louis	Missouri
United States	Novartis Investigator Site	Stockton	California
United States	Novartis Investigative Site	Topeka	Kansas
United States	Novartis Investigative Site	Tucson	Arizona
United States	Novartis Investigator Site	Walnut Creek	California
United States	Novartis Investigator Site	Wheat Ridge	Colorado

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Austria,  Belgium,  Canada,  Colombia,  Denmark,  Finland,  France,  Germany,  Greece,  Hungary,  Israel,  Italy,  Mexico,  Norway,  Poland,  Russian Federation,  Slovakia,  Spain,  Switzerland,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Trough Forced Expiratory Volume in 1 Second (FEV1) at End of Treatment (Week 12)	Spirometry was conducted according to internationally accepted standards. Trough FEV1 was defined as the average of the 23 hour 10 minute and 23 hour 45 minute post-dose FEV1 readings. Mixed model used baseline FEV1, FEV1 prior to and 10-15 minutes post inhalation of salbutamol/albuterol, FEV1 prior to and 1 hour post inhalation of ipratropium, and inhaled corticosteroid use at baseline as covariates.	End of treatment (Week 12)	No
Secondary	Forced Expiratory Volume in 1 Second (FEV1) Standardized (With Respect to Time) Area Under the Curve (AUC) From 5 Minutes to 4 Hours Post-dose at the End of Treatment (Week 12)	Spirometry was conducted according to internationally accepted standards. FEV1 was measured at 5 and 30 minutes; and 1, 2, and 4 hours post-dose on Week 12. Standardized FEV1 AUC (5 minutes-4 hour) post-dose at week 12 was calculated based on the trapezoidal rule, and was adjusted for the area per time unit by using the scheduled time of measurements for FEV1. Mixed model used baseline FEV1, FEV1 prior to and 10-15 minutes post inhalation of salbutamol/albuterol, FEV1 prior to and 1 hour post inhalation of ipratropium, and inhaled corticosteroid use at baseline as covariates.	5 minutes to 4 hours post-dose at the end of treatment (week 12)	No
Secondary	Transition Dyspnea Index (TDI) Focal Score After 12 Weeks of Treatment	TDI focal score is based on three domains: functional impairment, magnitude of task and magnitude of effort. Each domain is scored from -3 (major deterioration) to 3 (major improvement) to give an overall TDI focal score of -9 to 9 with a negative score indicating a deterioration from baseline. A 1 unit difference in the TDI focal score is clinically significant. Mixed model used baseline dyspnea index, FEV1 prior to and 10-15 minutes post inhalation of salbutamol/albuterol, FEV1 prior to and 1 hour post inhalation of ipratropium, and inhaled corticosteroid use at baseline as covariates.	12 weeks	No
Secondary	Quality of Life Assessment With St. George's Respiratory Questionnaire (SGRQ) Total Score After 12 Weeks of Treatment	SGRQ is a health related quality of life questionnaire consisting of 50 items in three domains: symptoms (frequency and severity), activity (that cause or are limited by breathlessness) and impacts (social functioning & psychological disturbances resulting from airway disease). The total score is 0 to 100 with a higher score indicating greater impairment of health status. Mixed model used baseline SGRQ, FEV1 prior to and 10-15 minutes post inhalation of salbutamol/albuterol, FEV1 prior to and 1 hour post inhalation of ipratropium, and inhaled corticosteroid use at baseline as covariates.	12 weeks	No
Secondary	Change From Baseline in the Mean Number of Puffs Per Day of Rescue Medication Over the Study Duration (From Day 1 to Week 12)	Participants recorded the number of puffs of rescue medication taken in the previous 12 hours each morning and evening in an electronic diary. The number of puffs per day over the 12 weeks of treatment was divided by the number of days to derive the mean number per day of puffs of rescue medication for each participant. Mixed model used baseline number of puffs per day of rescue medication, FEV1 prior to and 10-15 minutes post inhalation of salbutamol/albuterol, FEV1 prior to and 1 hour post inhalation of ipratropium, and inhaled corticosteroid use at baseline as covariates.	Baseline, up to 12 weeks	No
Secondary	Change From Baseline in the Mean Number Per Day of Daytime Puffs of Rescue Medication Over the Study Duration (From Day 1 to Week 12)	Participants recorded the number of puffs of rescue medication taken in the previous 12 hours each evening in an electronic diary. The number of daytime puffs per day over the 12 weeks of treatment was divided by the number of days to derive the mean number per day of daytime puffs of rescue medication for each participant. Mixed model used baseline number of daytime puffs per day of rescue medication, FEV1 prior to and 10-15 minutes post inhalation of salbutamol/albuterol, FEV1 prior to and 1 hour post inhalation of ipratropium, and inhaled corticosteroid use at baseline as covariates.	Baseline, up to 12 weeks	No
Secondary	Change From Baseline in the Mean Number Per Day of Nighttime Puffs of Rescue Medication Over the Study Duration (From Day 1 to Week 12)	Participants recorded the number of puffs of rescue medication taken in the previous 12 hours each morning in an electronic diary. The number of nighttime puffs per day over the 12 weeks of treatment was divided by the number of days to derive the mean number per day of nighttime puffs of rescue medication for each participant. Mixed model used baseline number of nighttime puffs per day of rescue medication, FEV1 prior to and 10-15 minutes post inhalation of salbutamol/albuterol, FEV1 prior to and 1 hour post inhalation of ipratropium, and inhaled corticosteroid use at baseline as covariates.	Baseline, up to 12 weeks	No
Secondary	Percentage of Days With no Rescue Medication Use During the 12 Weeks of Treatment	A day with no rescue medication was defined as any day in the diary that the participant used no puffs of rescue medication. The percentage of days with no rescue medication was calculated by dividing the number of days with no rescue medication over the 12 week treatment period by the number of evaluable days and multiplying by 100. Mixed model used baseline percentage of days with no rescue medication, FEV1 prior to and 10-15 minutes post inhalation of salbutamol/albuterol, FEV1 prior to and 1 hour post inhalation of ipratropium, and inhaled corticosteroid use at baseline as covariates.	Up to 12 weeks	No