Efficacy and Safety of Indacaterol Plus Tiotropium Versus Tiotropium Alone in Patients With Chronic Obstructive Pulmonary Disease

Chronic Obstructive Pulmonary Disease (COPD) Clinical Trial

— INTRUST2  

Official title:

A Randomized, Double-blind, Controlled, Parallel-group, 12-week Study to Compare the Efficacy and Safety of the Combination of Indacaterol 150 µg Once Daily With Open Label Tiotropium 18 µg Once Daily Versus Open Label Tiotropium 18 µg Once Daily in Patients With Moderate-to-severe Chronic Obstructive Pulmonary Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00877383
• Other study ID #: CQAB149B2351
• Status: Completed
• Phase: Phase 3
• First received: April 6, 2009
• Last updated: August 23, 2011
• Start date: April 2009
• Est. completion date: February 2010

Study information

• Verified date: August 2011
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationNetherlands: The Central Committee on Research Involving Human Subjects (CCMO)Slovakia: State Institute for Drug ControlCanada: Health CanadaCzech Republic: State Institute for Drug ControlHungary: National Institute of PharmacySpain: Spanish Agency of MedicinesColombia: INVIMA Instituto Nacional de Vigilancia de Medicamentos y AlimentosIndia: Drugs Controller General of India
• Study type: Interventional

Clinical Trial Summary

This study assessed the efficacy and safety of indacaterol (150 µg once daily [od]) when combined with tiotropium (18 µg od) versus tiotropium (18 µg od) treatment alone in patients with chronic obstructive pulmonary disease (COPD).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1142
• Est. completion date: February 2010
• Est. primary completion date: February 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years and older

Eligibility

Inclusion Criteria:

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

• Smoking history of at least 10 pack-years

• Post-bronchodilator forced expiratory volume in 1 second (FEV1) = 65% and = 30% of the predicted normal value

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

Exclusion Criteria:

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

• 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 (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

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

Intervention

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

Locations

Country	Name	City	State
Canada	Novartis Investigator Site	Gatineau
Canada	Novartis Investigator Site	Joliette
Canada	Novartis Investigator Site	Mirabel
Canada	Novartis Investigator Site	Mississauga
Canada	Novartis Investigator Site	Montreal
Canada	Novartis Investigative Site	Quebec
Canada	Novartis Investigator Site	Sainte-Foy
Canada	Novartis Investigator Site	Sherbrooke
Canada	Novartis Investigator Site	St-Jerome
Canada	Novartis Investigator Site	Toronto
Canada	Novartis Investigator Site	Trois-Rivières
Canada	Novartis Investigator Site	Windsor
Colombia	Novartis Investigative Site	Armenia
Colombia	Novartis Investigator Site	Barranquilla
Colombia	Novartis Investigative Site	Bogota
Colombia	Novartis Investigator Site	Cali
Czech Republic	Novartis Investigative Site	Karlovy Vary
Czech Republic	Novartis Investigative Site	Kladno
Czech Republic	Novartis Investigative Site	Kromeriz
Czech Republic	Novartis Investigative SIte	Liberec
Czech Republic	Novartis Investigative Site	Rokycany
Czech Republic	Novartis Investigative Site	Strakonice
Czech Republic	Novartis Investigative Site	Trebic
Hungary	Novartis Investigative Site	Erd
Hungary	Novartis Investigative Site	Füzesabony
Hungary	Novartis Investigator Site	Gyor
Hungary	Novartis Investgative Site	Százhalombatta
India	Novartis Investigator Site	Ahmedabad
India	Novartis Investigator Site	Bangalore
India	Novartis Investigator Site	Coimbatore
India	Novartis Investigative Site	Hyderabad
India	Novartis Investigative Site	Indore
India	Novartis Investigative Site	Jaipur
India	Novartis Investigator Site	Ludhiana
India	Novartis Investigative Site	Panjim
India	Novartis Investigator Site	Trivandrum
Netherlands	Novartis Investigative Site	Almelo
Netherlands	Novartis Investigative Site	Breda
Netherlands	Novartis Investigative Site	Heerlen
Netherlands	Novartis Investigative Site	Helmond
Netherlands	Novartis Investigative Site	Veldhoven
Netherlands	Novartis Investigative Site	Zutphen
Slovakia	Novartis Investigative Site	Štúrovo
Slovakia	Novartis Investigative Site	Banska Bystrica
Slovakia	Novartis Investigative Site	Bardejov
Slovakia	Novartis Investigative Site	Bratislava
Slovakia	Novartis Investigator Site	Bratislava
Slovakia	Novartis Investigative Site	Martin
Slovakia	Novartis Investigative Site	Poprad
Slovakia	Novartis Investigative Site	Povazska Bystrica
Spain	Novartis Investigative Site	Alicante
Spain	Novartis Investigative Site	Almeria
Spain	Novartis Investigative Site	Baracaldo
Spain	Novartis Investigator Site	Madrid
Spain	Novartis Investigative Site	Palma de Mallorca
Spain	Novartis Investigator Site	Pozuelo de Alarcón
Spain	Novartis Investigator Site	Riudecols
Spain	Novartis Investigative Site	San Boi De Llobregat
Spain	Novartis Investigator Site	Sevilla
Spain	Novartis Investigative Site	Vilassar de Mar
United States	Novartis Investigative Site	Abingdon	Virginia
United States	Novartis Investigative Site	Akron	Ohio
United States	Novartis Investigative Site	Allentown	Pennsylvania
United States	Novartis Investigator Site	Anniston	Alabama
United States	Novartis Investigative Site	Bayside	New York
United States	Novartis Investigative Site	Beaver	Pennsylvania
United States	Novartis Investigator Site	Bellevue	Nebraska
United States	Novartis Investigator Site	Billings	Montana
United States	Novartis Investigator Site	Birmingham	Alabama
United States	Novartis Investigator Site	Boulder	Colorado
United States	Novartis Investigative Site	Brick	New Jersey
United States	Novartis Investigator Site	Buena Park	California
United States	Novartis Investigative Site	Burlington	North Carolina
United States	Novartis Investigative Site	Burlington	Massachusetts
United States	Novartis Investigator Site	Centennial	Colorado
United States	Novartis Investigator Site	Charleston	South Carolina
United States	Novartis Investigator Site	Charlotte	North Carolina
United States	Novartis Investigator Site	Charlotte	North Carolina
United States	Novartis Investigator Site	Chaska	Minnesota
United States	Novartis Investigator Site	Cincinnati	Ohio
United States	Novartis Investigator Site	Cincinnati	Ohio
United States	Novartis Investigator Site	Clearwater	Florida
United States	Novartis Investigator Site	Cleveland	Ohio
United States	Novartis Investigator Site	Colorado Springs	Colorado
United States	Novartis Investigator Site	Columbia	Missouri
United States	Novartis Investigator Site	Couer D'Alene	Idaho
United States	Novartis Investigator Site	Crescent Springs	Kentucky
United States	Novartis Investigator Site	Dallas	Texas
United States	Novartis Investigator Site	Dallas	Texas
United States	Novartis Investigator Site	Denver	Colorado
United States	Novartis Investigator Site	Destin	Florida
United States	Novartis Investigator Site	Downers Grove	Illinois
United States	Novartis Investigator Site	Easley	South Carolina
United States	Novartis Investigator Site	Edina	Minnesota
United States	Novartis Investigator Site	Elk Grove Village	Illinois
United States	Novartis Investigative Site	Erie	Pennsylvania
United States	Novartis Investigator Site	Eugene	Oregon
United States	Novartis Investigator Site	Fargo	North Dakota
United States	Novartis Investigator Site	Fort Worth	Texas
United States	Novartis Investigative Site	Fredericks	Virginia
United States	Novartis Investigator Site	Fullerton	California
United States	Novartis Investigative Site	Glastonbury	Connecticut
United States	Novartis Investigator Site	Glendale	Arizona
United States	Novartis Investigator Site	Grand Forks	North Dakota
United States	Novartis Investigative Site	Great Neck	New York
United States	Novartis Investigator Site	Greenville	South Carolina
United States	Novartis Investigator Site	Henderson	Nevada
United States	Novartis Investigator Site	Houston	Texas
United States	Novartis Investigator Site	Jasper	Alabama
United States	Novartis Investigator Site	Kalispell	Montana
United States	Novartis Investigator Site	Kansas City	Missouri
United States	Novartis Investigative site	Larchmont	New York
United States	Novartis Investigator Site	Lexington	Kentucky
United States	Novartis Investigator Site	Lincoln	Nebraska
United States	Novartis Investigator Site	Little Rock	Arkansas
United States	Novartis Investigator Site	Louisville	Kentucky
United States	Novartis Investigator Site	Maitland	Florida
United States	Novartis Investigator Site	Miami	Florida
United States	Novartis Investigator Site	Miami Beach	Florida
United States	Novartis Investigative Site	Minneapolis	Minnesota
United States	Novartis Investigator Site	Mission Viejo	California
United States	Novartis Investigator Site	Mobile	Alabama
United States	Novartis Investigative Site	Morgantown	West Virginia
United States	Novartis Investigative Site	New Brunswick	New Jersey
United States	Novartis Investigator Site	North Charleston	South Carolina
United States	Novartis Investigator Site	Ocala	Florida
United States	Novartis Investigative Site	Ocean	New Jersey
United States	Novartis Investigator Site	Oklahoma City	Oklahoma
United States	Novartis Investigator Site	Ozark	Missouri
United States	Novartis Investigator Site	Papillion	Nebraska
United States	Novartis Investigative Site	Pawtucket	Rhode Island
United States	Novartis Investigator Site	Pensacola	Florida
United States	Novartis Investigator Site	Pensacola	Florida
United States	Novartis Investigator Site	Pensacola	Florida
United States	Novartis Investigative site	Philadelphia	Pennsylvania
United States	Novartis Investigative Site	Philadelphia	Pennsylvania
United States	Novartis Investigator Site	Phoenix	Arizona
United States	Novartis Investigator Site	Phoenix	Arizona
United States	Novartis Investigative Site	Phoenixville	Pennsylvania
United States	Novartis Investigator Site	Port Orange	Florida
United States	Novartis Investigative Site	Providence	Rhode Island
United States	Novartis Investigative Center	Raleigh	North Carolina
United States	Novartis Investigator Site	Renton	Washington
United States	Novartis Investigator Site	River Forest	Illinois
United States	Novartis Investigator Site	Rochester	Minnesota
United States	Novartis Investigator Site	Salt Lake City	Utah
United States	Novartis Investigator Site	San Ramon	California
United States	Novartis Investigator Site	Santa Barbara	California
United States	Novartis Investigator Site	Scottsdale	Arizona
United States	Novartis Investigator Site	Sepulveda	California
United States	Novartis Investigator Site	Shawnee	Kansas
United States	Novartis Investigative Site	Shelby	North Carolina
United States	Novartis Investigator Site	Shreveport	Louisiana
United States	Novartis Investigator Site	South Miami	Florida
United States	Novartis Investigator Site	Spartanburg	South Carolina
United States	Novartis Investigator Site	Spokane	Washington
United States	Novartis Investigator Site	Spring Valley	California
United States	Novartis Investigator Site	Springfield	Illinois
United States	Novartis Investigator Site	St Paul	Minnesota
United States	Novartis Investigator Site	St. Louis	Missouri
United States	Novartis Investigator Site	St. Louis	Missouri
United States	Novartis Investigator Site	St. Louis	Missouri
United States	Novartis Investigator Site	Statesville	North Carolina
United States	Novartis Investigator Site	Tamarac	Florida
United States	Novartis Investigator Site	Tampa	Florida
United States	Novartis Investigator Site	Tampa	Florida
United States	Novartis Investigator Site	Toledo	Ohio
United States	Novartis Investigator Site	Torrance	California
United States	Novartis Investigator Site	Torrance	California
United States	Novartis Investigator Site	Troy	Michigan
United States	Novartis Investigator Site	Tyler	Texas
United States	Novartis Investigator Site	Union	South Carolina
United States	Novartis Investigator Site	Vista	California
United States	Novartis Investigative Site	Waldorf	Maryland
United States	Novartis Investigative Site	Waterbury	Connecticut
United States	Novartis Investigative Site	Winston Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Canada,  Colombia,  Czech Republic,  Hungary,  India,  Netherlands,  Slovakia,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Forced Expiratory Volume in 1 Second (FEV1) Standardized (With Respect to Length of Time) Area Under the Curve (AUC) From 5 Minutes to 8 Hours Post-dose at the End of the Study (Week 12, Day 84)	FEV1 was measured with spirometry conducted according to internationally accepted standards. Measurements were made at 5 and 30 minutes; and 1, 2, 3, 4, 6, and 8 hours post-dose at the end of the study (Week 12, Day 84). The standardized AUC FEV1 was calculated as the sum of trapezoids divided by the length of time. The analysis included baseline FEV1, FEV1 pre-dose and 10-15 minutes post-dose of salbutamol/albuterol during screening, and FEV1 pre-dose and 1 hour post-dose of ipratropium during screening as covariates.	From 5 minutes to 8 hours post-dose at the end of the study (Week 12, Day 84)	No
Secondary	Trough Forced Expiratory Volume in 1 Second (FEV1) 24 Hours Post-dose at the End of the Study (Week 12 + 1 Day, Day 85)	FEV1 was measured with spirometry conducted according to internationally accepted standards. Trough FEV1 was defined as the average of measurements made 23 hours 10 minutes and 23 hours 45 minutes post-dose at the end of the study. The analysis included baseline FEV1, FEV1 pre-dose and 10-15 minutes post-dose of salbutamol/albuterol during screening, and FEV1 pre-dose and 1 hour post-dose of ipratropium during screening as covariates.	End of the study (Week 12 + 1 day, Day 85)	No
Secondary	Forced Expiratory Volume in 1 Second (FEV1) Standardized (With Respect to Length of Time) Area Under the Curve (AUC) From 5 Minutes to 8 Hours Post-dose on Day 1	FEV1 was measured with spirometry conducted according to internationally accepted standards. Measurements were made at 5 and 30 minutes; and 1, 2, 3, 4, 6, and 8 hours post-dose on Day 1. The standardized AUC FEV1 was calculated as the sum of trapezoids divided by the length of time. The analysis included baseline FEV1, FEV1 pre-dose and 10-15 minutes post-dose of salbutamol/albuterol during screening, and FEV1 pre-dose and 1 hour post-dose of ipratropium during screening as covariates.	From 5 minutes to 8 hours post-dose on Day 1	No
Secondary	Trough Forced Expiratory Volume in 1 Second (FEV1) 24 Hours Post-dose on Day 2	FEV1 was measured with spirometry conducted according to internationally accepted standards. Trough FEV1 was defined as the average of measurements made 23 hours 10 minutes and 23 hours 45 minutes post-dose on Day 2. The analysis included baseline FEV1, FEV1 pre-dose and 10-15 minutes post-dose of salbutamol/albuterol during screening, and FEV1 pre-dose and 1 hour post-dose of ipratropium during screening as covariates.	24 hours post-dose on Day 2	No
Secondary	Forced Expiratory Volume in 1 Second (FEV1) Standardized (With Respect to Length of Time) Area Under the Curve (AUC) From 5 Minutes to 4 Hours Post-dose on Day 1	FEV1 was measured with spirometry conducted according to internationally accepted standards. Measurements were made at 5 and 30 minutes; and 1, 2, 3, and 4 hours post-dose on Day 1. The standardized AUC FEV1 was calculated as the sum of trapezoids divided by the length of time. The analysis included baseline FEV1, FEV1 pre-dose and 10-15 minutes post-dose of salbutamol/albuterol during screening, and FEV1 pre-dose and 1 hour post-dose of ipratropium during screening as covariates.	From 5 minutes to 4 hours post-dose on Day 1	No
Secondary	Forced Expiratory Volume in 1 Second (FEV1) Standardized (With Respect to Length of Time) Area Under the Curve (AUC) From 5 Minutes to 4 Hours Post-dose at the End of the Study (Week 12, Day 84)	FEV1 was measured with spirometry conducted according to internationally accepted standards. Measurements were made at 5 and 30 minutes; and 1, 2, 3, and 4 hours post-dose at the end of the study (Week 12, Day 84). The standardized AUC FEV1 was calculated as the sum of trapezoids divided by the length of time. The analysis included baseline FEV1, FEV1 pre-dose and 10-15 minutes post-dose of salbutamol/albuterol during screening, and FEV1 pre-dose and 1 hour post-dose of ipratropium during screening as covariates.	From 5 minutes to 4 hours post-dose at the end of the study (Week 12, Day 84)	No