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

NCT00877383 | Completed Phase 3 Results

• 1 other identifier: CQAB149B2351
• Study Type: interventional
• Target: 1,142
• Locations: 9 countries
• Sites: 176

Brief 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).

Conditions

Chronic Obstructive Pulmonary Disease (COPD)

Keywords

chronic obstructive pulmonary disease; COPD; indacaterol; tiotropium; bronchodilation

Outcome Measures

Primary Outcomes (1)

• 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)

Secondary Outcomes (5)

• Trough Forced Expiratory Volume in 1 Second (FEV1) 24 Hours Post-dose at the End of the Study (Week 12 + 1 Day, Day 85)

  End of the study (Week 12 + 1 day, Day 85)

• 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

  From 5 minutes to 8 hours post-dose on Day 1

• Trough Forced Expiratory Volume in 1 Second (FEV1) 24 Hours Post-dose on Day 2

  24 hours post-dose on Day 2

• 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

  From 5 minutes to 4 hours post-dose on Day 1

• 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)

  From 5 minutes to 4 hours post-dose at the end of the study (Week 12, Day 84)

Study Arms (2)

Indacaterol 150 μg and tiotropium 18 μg

EXPERIMENTAL

Patients inhaled indacaterol 150 μg and tiotropium 18 μg once daily in the morning between 8:00 AM and 11:00 AM for 12 weeks. Indacaterol was delivered blinded via a single-dose dry-powder inhaler (SDDPI). Tiotropium was delivered open-label via the manufacturer's proprietary inhalation device (HandiHaler®). Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.

Drug: Indacaterol 150 μg; Drug: Tiotropium 18 μg

Tiotropium 18 μg

ACTIVE COMPARATOR

Patients inhaled placebo to indacaterol 150 μg and tiotropium 18 μg once daily in the morning between 8:00 AM and 11:00 AM for 12 weeks. Placebo to indacaterol was delivered blinded via a single-dose dry-powder inhaler (SDDPI). Tiotropium was delivered open-label via the manufacturer's proprietary inhalation device (HandiHaler®). Daily inhaled corticosteroid treatment (if applicable) was to remain stable throughout the study. The short-acting β2-agonist salbutamol/albuterol was available for rescue use throughout the study.

Drug: Tiotropium 18 μg; Drug: Placebo to indacaterol

Interventions

Indacaterol 150 μg DRUG

Indacaterol was supplied in powder filled capsules together with a single-dose dry-powder inhaler (SDDPI) device.

Indacaterol 150 μg and tiotropium 18 μg

Tiotropium 18 μg DRUG

Tiotropium was supplied in powder filled capsules together with the manufacturer's proprietary inhalation device (HandiHaler®).

Indacaterol 150 μg and tiotropium 18 μg; Tiotropium 18 μg

Placebo to indacaterol DRUG

Placebo to indacaterol was supplied in powder filled capsules together with a single-dose dry-powder inhaler (SDDPI) device.

Tiotropium 18 μg

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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%

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (176)

Novartis Investigator Site

Anniston, Alabama, 36207-5710, United States

Location

Novartis Investigator Site

Birmingham, Alabama, 35249-2181, United States

Location

Novartis Investigator Site

Jasper, Alabama, 35501, United States

Location

Novartis Investigator Site

Mobile, Alabama, 36608-1128, United States

Location

Novartis Investigator Site

Glendale, Arizona, 85306, United States

Location

Novartis Investigator Site

Phoenix, Arizona, 85006, United States

Location

Novartis Investigator Site

Phoenix, Arizona, 85013, United States

Location

Novartis Investigator Site

Scottsdale, Arizona, 85251, United States

Location

Novartis Investigator Site

Little Rock, Arkansas, 72205, United States

Location

Novartis Investigator Site

Buena Park, California, 90620, United States

Location

Novartis Investigator Site

Fullerton, California, 92835, United States

Location

Novartis Investigator Site

Mission Viejo, California, 92691, United States

Location

Novartis Investigator Site

San Ramon, California, 94583, United States

Location

Novartis Investigator Site

Santa Barbara, California, 93110, United States

Location

Novartis Investigator Site

Sepulveda, California, 91343, United States

Location

Novartis Investigator Site

Spring Valley, California, 91978, United States

Location

Novartis Investigator Site

Torrance, California, 90502, United States

Location

Novartis Investigator Site

Torrance, California, 90505, United States

Location

Novartis Investigator Site

Vista, California, 92083, United States

Location

Novartis Investigator Site

Boulder, Colorado, 80304, United States

Location

Novartis Investigator Site

Centennial, Colorado, 80112, United States

Location

Novartis Investigator Site

Colorado Springs, Colorado, 80907, United States

Location

Novartis Investigator Site

Denver, Colorado, 80206, United States

Location

Novartis Investigative Site

Glastonbury, Connecticut, 06033, United States

Location

Novartis Investigative Site

Waterbury, Connecticut, 06708, United States

Location

Novartis Investigator Site

Clearwater, Florida, 33765, United States

Location

Novartis Investigator Site

Destin, Florida, 32541, United States

Location

Novartis Investigator Site

Maitland, Florida, 32751, United States

Location

Novartis Investigator Site

Miami, Florida, 33125, United States

Location

Novartis Investigator Site

Miami Beach, Florida, 33140, United States

Location

Novartis Investigator Site

Ocala, Florida, 34471, United States

Location

Novartis Investigator Site

Pensacola, Florida, 32503, United States

Location

Novartis Investigator Site

Pensacola, Florida, 32504, United States

Location

Novartis Investigator Site

Pensacola, Florida, 32514, United States

Location

Novartis Investigator Site

Port Orange, Florida, 32127, United States

Location

Novartis Investigator Site

South Miami, Florida, 33143, United States

Location

Novartis Investigator Site

Tamarac, Florida, 33321, United States

Location

Novartis Investigator Site

Tampa, Florida, 33603, United States

Location

Novartis Investigator Site

Tampa, Florida, 33613, United States

Location

Novartis Investigator Site

Couer D'Alene, Idaho, 98314, United States

Location

Novartis Investigator Site

Downers Grove, Illinois, 60515, United States

Location

Novartis Investigator Site

Elk Grove Village, Illinois, 60007, United States

Location

Novartis Investigator Site

River Forest, Illinois, 60305, United States

Location

Novartis Investigator Site

Springfield, Illinois, 62781, United States

Location

Novartis Investigator Site

Shawnee, Kansas, 66217, United States

Location

Novartis Investigator Site

Crescent Springs, Kentucky, 41017, United States

Location

Novartis Investigator Site

Lexington, Kentucky, 40504, United States

Location

Novartis Investigator Site

Louisville, Kentucky, 40202, United States

Location

Novartis Investigator Site

Shreveport, Louisiana, 71103, United States

Location

Novartis Investigative Site

Waldorf, Maryland, 20602, United States

Location

Novartis Investigative Site

Burlington, Massachusetts, 01803, United States

Location

Novartis Investigator Site

Troy, Michigan, 48085, United States

Location

Novartis Investigator Site

Chaska, Minnesota, 55318, United States

Location

Novartis Investigator Site

Edina, Minnesota, 55435, United States

Location

Novartis Investigative Site

Minneapolis, Minnesota, 55402, United States

Location

Novartis Investigator Site

Rochester, Minnesota, 55905, United States

Location

Novartis Investigator Site

Saint Paul, Minnesota, 55130, United States

Location

Novartis Investigator Site

Columbia, Missouri, 65212, United States

Location

Novartis Investigator Site

Kansas City, Missouri, 64128, United States

Location

Novartis Investigator Site

Ozark, Missouri, 65721, United States

Location

Novartis Investigator Site

St Louis, Missouri, 63110, United States

Location

Novartis Investigator Site

St Louis, Missouri, 63141, United States

Location

Novartis Investigator Site

St Louis, Missouri, 63317, United States

Location

Novartis Investigator Site

Billings, Montana, 59102, United States

Location

Novartis Investigator Site

Kalispell, Montana, 59901, United States

Location

Novartis Investigator Site

Bellevue, Nebraska, 68005, United States

Location

Novartis Investigator Site

Lincoln, Nebraska, 68516, United States

Location

Novartis Investigator Site

Papillion, Nebraska, 68046, United States

Location

Novartis Investigator Site

Henderson, Nevada, 89014, United States

Location

Novartis Investigative Site

Brick, New Jersey, 08723, United States

Location

Novartis Investigative Site

New Brunswick, New Jersey, 08902, United States

Location

Novartis Investigative Site

Ocean City, New Jersey, 07712, United States

Location

Novartis Investigative Site

Bayside, New York, 11361, United States

Location

Novartis Investigative Site

Great Neck, New York, 11023, United States

Location

Novartis Investigative site

Larchmont, New York, 10538, United States

Location

Novartis Investigative Site

Burlington, North Carolina, 27215, United States

Location

Novartis Investigator Site

Charlotte, North Carolina, 28207, United States

Location

Novartis Investigator Site

Charlotte, North Carolina, 28277, United States

Location

Novartis Investigative Center

Raleigh, North Carolina, 27607, United States

Location

Novartis Investigative Site

Shelby, North Carolina, 28150, United States

Location

Novartis Investigator Site

Statesville, North Carolina, 28625, United States

Location

Novartis Investigative Site

Winston-Salem, North Carolina, 27103, United States

Location

Novartis Investigator Site

Fargo, North Dakota, 58103, United States

Location

Novartis Investigator Site

Grand Forks, North Dakota, 58201, United States

Location

Novartis Investigative Site

Akron, Ohio, 44313, United States

Location

Novartis Investigator Site

Cincinnati, Ohio, 45231, United States

Location

Novartis Investigator Site

Cincinnati, Ohio, 45242, United States

Location

Novartis Investigator Site

Cleveland, Ohio, 44109, United States

Location

Novartis Investigator Site

Toledo, Ohio, 43608, United States

Location

Novartis Investigator Site

Oklahoma City, Oklahoma, 73104, United States

Location

Novartis Investigator Site

Eugene, Oregon, 97401, United States

Location

Novartis Investigative Site

Allentown, Pennsylvania, 18103, United States

Location

Novartis Investigative Site

Beaver, Pennsylvania, 15009, United States

Location

Novartis Investigative Site

Erie, Pennsylvania, 16506, United States

Location

Novartis Investigative site

Philadelphia, Pennsylvania, 19104, United States

Location

Novartis Investigative Site

Philadelphia, Pennsylvania, 19140, United States

Location

Novartis Investigative Site

Phoenixville, Pennsylvania, 19460, United States

Location

Novartis Investigative Site

Pawtucket, Rhode Island, 02860, United States

Location

Novartis Investigative Site

Providence, Rhode Island, 02903, United States

Location

Novartis Investigator Site

Charleston, South Carolina, 29407, United States

Location

Novartis Investigator Site

Easley, South Carolina, 26940, United States

Location

Novartis Investigator Site

Greenville, South Carolina, 29615, United States

Location

Novartis Investigator Site

North Charleston, South Carolina, 29406-7108, United States

Location

Novartis Investigator Site

Spartanburg, South Carolina, 29303, United States

Location

Novartis Investigator Site

Union, South Carolina, 29379, United States

Location

Novartis Investigator Site

Dallas, Texas, 75216, United States

Location

Novartis Investigator Site

Dallas, Texas, 75246, United States

Location

Novartis Investigator Site

Fort Worth, Texas, 76109, United States

Location

Novartis Investigator Site

Houston, Texas, 77030, United States

Location

Novartis Investigator Site

Tyler, Texas, 75708, United States

Location

Novartis Investigator Site

Salt Lake City, Utah, 84107, United States

Location

Novartis Investigative Site

Abingdon, Virginia, 24210, United States

Location

Novartis Investigative Site

Fredericks, Virginia, 22401, United States

Location

Novartis Investigator Site

Renton, Washington, 98055, United States

Location

Novartis Investigator Site

Spokane, Washington, 99204, United States

Location

Novartis Investigative Site

Morgantown, West Virginia, 26505, United States

Location

Novartis Investigator Site

Gatineau, Canada

Location

Novartis Investigator Site

Joliette, Canada

Location

Novartis Investigator Site

Mirabel, Canada

Location

Novartis Investigator Site

Mississauga, Canada

Location

Novartis Investigator Site

Montreal, Canada

Location

Novartis Investigative Site

Québec, Canada

Location

Novartis Investigator Site

Saint-Jérôme, Canada

Location

Novartis Investigator Site

Sainte-Foy, Canada

Location

Novartis Investigator Site

Sherbrooke, Canada

Location

Novartis Investigator Site

Toronto, Canada

Location

Novartis Investigator Site

Trois-Rivières, Canada

Location

Novartis Investigator Site

Windsor, Canada

Location

Novartis Investigative Site

Armenia, Colombia

Location

Novartis Investigator Site

Barranquilla, Colombia

Location

Novartis Investigative Site

Bogotá, Colombia

Location

Novartis Investigator Site

Cali, Colombia

Location

Novartis Investigative Site

Karlovy Vary, Czechia

Location

Novartis Investigative Site

Kladno, Czechia

Location

Novartis Investigative Site

Kroměříž, Czechia

Location

Novartis Investigative SIte

Liberec, Czechia

Location

Novartis Investigative Site

Rokycany, Czechia

Location

Novartis Investigative Site

Strakonice, Czechia

Location

Novartis Investigative Site

Třebíč, Czechia

Location

Novartis Investigative Site

Érd, Hungary

Location

Novartis Investigative Site

Füzesabony, Hungary

Location

Novartis Investigator Site

Győr, Hungary

Location

Novartis Investgative Site

Százhalombatta, Hungary

Location

Novartis Investigator Site

Ahmedabad, India

Location

Novartis Investigator Site

Bangalore, India

Location

Novartis Investigator Site

Coimbatore, India

Location

Novartis Investigative Site

Hyderabad, India

Location

Novartis Investigative Site

Indore, India

Location

Novartis Investigative Site

Jaipur, India

Location

Novartis Investigator Site

Ludhiana, India

Location

Novartis Investigative Site

Panjim, India

Location

Novartis Investigator Site

Trivandrum, India

Location

Novartis Investigative Site

Almelo, Netherlands

Location

Novartis Investigative Site

Breda, Netherlands

Location

Novartis Investigative Site

Heerlen, Netherlands

Location

Novartis Investigative Site

Helmond, Netherlands

Location

Novartis Investigative Site

Veldhoven, Netherlands

Location

Novartis Investigative Site

Zutphen, Netherlands

Location

Novartis Investigative Site

Banská Bystrica, Slovakia

Location

Novartis Investigative Site

Bardejov, Slovakia

Location

Novartis Investigative Site

Bratislava, Slovakia

Location

Novartis Investigator Site

Bratislava, Slovakia

Location

Novartis Investigative Site

Martin, Slovakia

Location

Novartis Investigative Site

Poprad, Slovakia

Location

Novartis Investigative Site

Považská Bystrica, Slovakia

Location

Novartis Investigative Site

Štúrovo, Slovakia

Location

Novartis Investigative Site

Alicante, Spain

Location

Novartis Investigative Site

Almería, Spain

Location

Novartis Investigative Site

Barakaldo, Spain

Location

Novartis Investigator Site

Madrid, Spain

Location

Novartis Investigative Site

Palma de Mallorca, Spain

Location

Novartis Investigator Site

Pozuelo de Alarcón, Spain

Location

Novartis Investigator Site

Riudecols, Spain

Location

Novartis Investigative Site

San Boi de Llobregat, Spain

Location

Novartis Investigator Site

Seville, Spain

Location

Novartis Investigative Site

Vilassar de Mar, Spain

Location

Related Publications (1)

• Mahler DA, D'Urzo A, Bateman ED, Ozkan SA, White T, Peckitt C, Lassen C, Kramer B; INTRUST-1 and INTRUST-2 study investigators. Concurrent use of indacaterol plus tiotropium in patients with COPD provides superior bronchodilation compared with tiotropium alone: a randomised, double-blind comparison. Thorax. 2012 Sep;67(9):781-8. doi: 10.1136/thoraxjnl-2011-201140. Epub 2012 Apr 27.

  PMID: 22544891 DERIVED

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

indacaterol; Tiotropium Bromide

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Scopolamine Derivatives; Tropanes; Azabicyclo Compounds; Aza Compounds; Organic Chemicals; Alkaloids; Heterocyclic Compounds; Bridged Bicyclo Compounds, Heterocyclic; Heterocyclic Compounds, Bridged-Ring

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

862 778-8300

Study Officials

• Novartis Pharmaceticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 6, 2009
• First Posted: April 7, 2009
• Study Start: April 1, 2009
• Primary Completion: February 1, 2010
• Study Completion: February 1, 2010
• Last Updated: August 25, 2011
• Results First Posted: August 19, 2011

Record last verified: 2011-08

Locations

CZ (7); ES (10); HU (4); US (116); CA (12); IN (9); NL (6); SL (8); CO (4)