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

Chronic Obstructive Pulmonary Disease (COPD) Clinical Trial

— INTRUST1  

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: NCT00846586
• Other study ID #: CQAB149B2341
• Status: Completed
• Phase: Phase 3
• First received: February 15, 2009
• Last updated: July 22, 2011
• Start date: March 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 AdministrationDenmark: Danish Medicines AgencySpain: Spanish Agency of MedicinesTurkey: Ministry of HealthAustralia: Department of Health and Ageing Therapeutic Goods AdministrationSouth Africa: Medicines Control CouncilPhilippines: Bureau of Food and DrugsColombia: INVIMA Instituto Nacional de Vigilancia de Medicamentos y AlimentosGuatemala: Comisión para la Evaluación de Ensayos Clínicos Ministerio de Salud Pública y Asistencia SocialArgentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
• 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: 1134
• 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 chronic obstructive pulmonary disease (COPD) (moderate-to-severe as classified by the Global Initiative for Chronic Obstructive Lung Disease [GOLD] Guidelines, 2007) and:

1. Smoking history of at least 10 pack-years

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

3. Post-bronchodilator FEV1/FVC (force vital capacity) < 70%

Exclusion Criteria:

• Patients who have had a COPD exacerbation requiring systemic glucocorticosteroid treatment or antibiotics and/or hospitalization 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 or during the run-in period

• Patients with a body mass index less than 15 or more than 40 kg/m^2

• 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 the manufacture'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
Argentina	Novartis Investigative Site	Buenos Aires
Argentina	Novartis Investigative Site	Cordoba
Argentina	Novartis Investigative Site	Corrientes
Argentina	Novartis Investigative SIte	Mendoza
Argentina	Novartis Investigative Site	Rosario
Australia	Novartis Investigator Site	Box Hill
Australia	Novartis Investigator Site	Clayton
Australia	Novartis Investigator Site	Garran
Australia	Novartis Investigator Site	Glebe
Australia	Novartis Investigator Site	Kogarah
Australia	Novartis Investigator Site	Nedlands
Colombia	Novartis Investigative Site	Barranquilla
Colombia	Novartis Investigative Site	Bogota
Colombia	Novartis Investigator Site	Bogota
Colombia	Novartis Investigative Site	Medellin
Denmark	Novartis Investigator Site	Copenhagen
Denmark	Novartis Investigator Site	Fredericia
Denmark	Novartis Investigator Site	Silkeborg
Denmark	Novartis Investigator Site	Soeborg
Denmark	Novartis Investigator Site	Vejle
Germany	Novartis Investigator Site	Berlin
Germany	Novartis Investigator Site	Cottbus
Germany	Novartis Investigator Site	Donaustauf
Germany	Novartis Investigator Site	Dortmund
Germany	Novartis Investigator Site	Erfurt
Germany	Novartis Investigator Site	Frankfurt
Germany	Novartis Investigator Site	Gelnhausen
Germany	Novartis Investigator Site	Grosshansdorf
Germany	Novartis Investigator Site	Hannover
Germany	Novartis Investigator Site	Heidelberg
Germany	Novartis Investigator Site	Leipzig
Germany	Novartis Investigator Site	Mainz
Germany	Novartis Investigator Site	Neu-Ulm
Germany	Novartis Investigator Site	Neuss
Germany	Novartis Investigator Site	Potsdam
Germany	Novartis Investigator Site	Rostock
Germany	Novartis Investigator Site	Schwabach
Germany	Novartis Investigator Site	Schwetzingen
Germany	Novartis Investigator Site	Straussberg
Germany	Novartis Investigative Site	Wiesbaden
Germany	Novartis Investigator Site	Wuppertal
Guatemala	Novartis Investigative Site	Guatemala
Guatemala	Novartis Investigative Site	Guatemala City
Mexico	Novartis Investigative Site	Guadalajara
Mexico	Novartis Investigator Site	Mexico City
Mexico	Novartis Investigative Site	Monterrey
Mexico	Novartis Investigative Site	Zapopan
Philippines	Novartis Investigator Site	Manila
South Africa	Novartis Investigator Site	Amanzimtoti
South Africa	Novartis Investigator Site	Cape Town
South Africa	Novartis Investigator Site	Johannesburg
South Africa	Novartis Investigator Site	Midrand
South Africa	Novartis Investigator Site	Umkomaas
Spain	Novartis Investigative Site	Alicante
Spain	Novartis Investigator Site	Barcelona
Spain	Novartis Investigator Site	Begonte
Spain	Novartis Investigator Site	Cadiz
Spain	Novartis Investigator Site	Granollers
Spain	Novartis Investigative Site	Jaén
Spain	Novartis Investigator Site	La Coruna
Spain	Novartis Investigator Site	Leon
Spain	Novartis Investigator Site	Madrid
Spain	Novartis Investigator Site	Pamplona
Spain	Novartis Investigator Site	Torrelavega
Spain	Novartis Investigator Site	Valencia
Spain	Novartis Investigator Site	Vigo
Turkey	Novartis Investigator Site	Antalya
Turkey	Novartis Investigator Site	Canakkale
Turkey	Novartis Investigator Site	Isparta
Turkey	Novartis Investigator Site	Istanbul
Turkey	Novartis Investigator Site	Kartal
Turkey	Novartis Investigator Site	Kayseri
Turkey	Novartis Investigator Site	Kozlu / Zonguldak
Turkey	Novartis Investigator Site	Malatya
Turkey	Novartis Investigator Site	Manisa
Turkey	Novartis Investigator Site	Mecidiyekoy/Istanbul
Turkey	Novartis Investigator Site	Yenisehir/Izmir
United States	Novartis Investigator Site	Asbury Park	New Jersey
United States	Novartis Investigative Site	Atlanta	Georgia
United States	Novartis Investigator Site	Bethlehem	Pennsylvania
United States	Novartis Investigator Site	Birmingham	Alabama
United States	Novartis Investigator Site	Boys Town	Nebraska
United States	Novartis Investigator Site	Brockton	Massachusetts
United States	Novartis Investigator Site	Clarkston	Michigan
United States	Novartis Investigative Site	Clearwater	Florida
United States	Novartis Investigator Site	Columbia	Maryland
United States	Novartis Investigator Site	Conyers	Georgia
United States	Novartis Investigative Site	Cumberland	Rhode Island
United States	Novartis Investigator Site	Detroit	Michigan
United States	Novartis Investigator Site	El Paso	Texas
United States	Novartis Investigator Site	Fountain Valley	California
United States	Novartis Investigator Site	Ft. Walton Beach	Florida
United States	Novartis Investigator Site	Greenville	South Carolina
United States	Novartis Investigative Site	Hartford	Connecticut
United States	Novartis Investigative Site	Houston	Texas
United States	Novartis Investigative Site	Houston	Texas
United States	Novartis Investigative Site	Iowa City	Iowa
United States	Novartis Investigative Site	Kansas City	Kansas
United States	Novartis Investigator Site	Knoxville	Tennessee
United States	Novartis Investigator Site	Lafayette	Louisiana
United States	Novartis Investigative Site	Las Vegas	Nevada
United States	Novartis Investigator Site	Lebanon	New Hampshire
United States	Novartis Investigative Site	Lenexa	Kansas
United States	Novartis Investigator Site	Long Beach	California
United States	Novartis Investigative Site	Los Angeles	California
United States	Novartis Investigative Site	Medford	Oregon
United States	Novartis Investigator Site	Metaire	Louisiana
United States	Novartis Investigative Site	Miami	Florida
United States	Novartis Investigative Site	Miami	Florida
United States	Novartis Investigator Site	Missoula	Montana
United States	Novartis Investigator Site	Mobile	Alabama
United States	Novartis Investigator Site	Mooresville	North Carolina
United States	Novartis Investigative Site	Naranja	Florida
United States	Novartis Investigator Site	National City	California
United States	Novartis Investigative Center	New Braunfels	Texas
United States	Novartis Investigator Site	New Orleans	Louisiana
United States	Novartis Investigator Site	Newport News	Virginia
United States	Novartis Investigative Site	Normal	Illinois
United States	Novartis Investigative Site	Omaha	Nebraska
United States	Novartis Investigative site	Omaha	Nebraska
United States	Novartis Investigator Site	Palmdale	California
United States	Novartis Investigator Site	Pensacola	Florida
United States	Novartis Investigator Site	Pine Bluff	Arkansas
United States	Novartis Investigative Site	Richmond	Virginia
United States	Novartis Investigator Site	Richmond	Virginia
United States	Novartis Investigative Site	Rochester	New York
United States	Novartis Investigator Site	Sarasota	Florida
United States	Novartis Investigative Site	Scottsdale	Arizona
United States	Novartis Investigator Site	Slidell	Louisiana
United States	Novartis Investigative Site	Spartanburg	South Carolina
United States	Novartis Investigative Site	St Charles	Missouri
United States	Novartis Investigative Site	Stockton	California
United States	Novartis Investigator Site	Temecula	California
United States	Novartis Investigative Site	Topeka	Kansas
United States	Novartis Investigative Site	Tucson	Arizona
United States	Novartis Investigative Site	Tucson	Arizona
United States	Novartis Investigator Site	Tulsa	Oklahoma
United States	Novartis Investigative Site	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Colombia,  Denmark,  Germany,  Guatemala,  Mexico,  Philippines,  South Africa,  Spain,  Turkey, 

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 Treatment (Week 12)	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). Standardized FEV1 AUC was calculated by the trapezoidal rule. 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 treatment (Week 12, Day 84)	No
Secondary	Trough Forced Expiratory Volume in 1 Second (FEV1) 24 Hours Post-dose at the End of Treatment (Week 12 + 1 Day, Day 85)	FEV1 was measured with spirometry conducted according to internationally accepted standards. Measurements were made at 23 hours 10 minutes and 23 hours 45 minutes post-dose at the end of the study (Week 12 + 1 day, Day 85). 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 at the end of treatment (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. Standardized FEV1 AUC was calculated by the trapezoidal rule. 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. Measurements were made at 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. Standardized FEV1 AUC was calculated by the trapezoidal rule. 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 Treatment (Week 12)	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 treatment (Week 12). Standardized FEV1 AUC was calculated by the trapezoidal rule. 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 treatment (Week 12)	No