A Dose Ranging Trial of 4 Doses of Indacaterol Delivered Via the TWISTHALER® Device in Patients With Chronic Obstructive Pulmonary Disease (COPD)

NCT00557466 | Completed Phase 2 Results

• 1 other identifier: CQMF149B2201
• Study Type: interventional
• Target: 568
• Locations: 17 countries
• Sites: 75

Brief Summary

This study will evaluate the dose response relationship among four doses of indacaterol as well as placebo delivered via the TWISTHALER® device.

Conditions

COPD

Keywords

QMF; indacaterol; TWISTHALER® device

Outcome Measures

Primary Outcomes (1)

• The Mean Change From Baseline to 24 Hour Post-dose (Trough) Forced Expiratory Volume in 1 Second (FEV1)

  FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. Change from baseline to 24 hour post dose trough FEV1 after 14 days of treatment was analyzed using Analysis of Covariance (ANCOVA) adjusting for treatment and region with baseline FEV1 as a covariate.

  Baseline (prior to first dose) and Day 15 (24 hours after last dose)

Secondary Outcomes (6)

• Standardized Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC) Between Baseline (Predose) and 4 Hours Post-dose

  Day 14, pre-dose and at 5, 20, 30 minutes and 1, 2, 3, and 4 hours post-dose.

• The Mean Change From Baseline to 24 Hour Post-dose (Trough) Forced Expiratory Volume in 1 Second (FEV1) on Day 1

  Day 1 Baseline (prior to first dose) and 24 hours post-dose.

• Standardized Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC) Between Baseline (Predose) and 4 Hours Post-dose on Day 1

  Day 1; pre-dose and at 5, 20, 30 minutes and 1, 2, 3, and 4 hours post-dose.

• Time to Peak Forced Expiratory Volume in 1 Second (FEV1) on Day 1 and Day 14

  Day 1 and Day 14 measured pre-dose and up to 4 hours post-dose

• Change From Baseline in Morning and Evening Peak Expiratory Flow

  Baseline (recorded during the screening period) and Days 1-14 (treatment period).

Study Arms (6)

indacaterol 62.5 μg

EXPERIMENTAL

Indacaterol 62.5 μg delivered by the TWISTHALER® device once a day and placebo to formoterol (placebo AEROLIZER® device) twice a day for 14 days. All participants were supplied with salbutamol/albuterol to use throughout the study as rescue medication.

Drug: indacaterol; Drug: placebo to formoterol; Drug: short acting β2- agonist

indacaterol 125 μg

EXPERIMENTAL

Indacaterol 125 μg delivered by the TWISTHALER® device once a day and placebo to formoterol (placebo AEROLIZER® device) twice a day for 14 days. All participants were supplied with salbutamol/albuterol to use throughout the study as rescue medication.

Drug: indacaterol; Drug: placebo to formoterol; Drug: short acting β2- agonist

Indacaterol 250 μg

EXPERIMENTAL

Indacaterol 250 μg delivered by the TWISTHALER® device once a day and placebo to formoterol (placebo AEROLIZER® device) twice a day for 14 days. All participants were supplied with salbutamol/albuterol to use throughout the study as rescue medication.

Drug: indacaterol; Drug: placebo to formoterol; Drug: short acting β2- agonist

indacaterol 500 μg

EXPERIMENTAL

Indacaterol 500 μg delivered by the TWISTHALER® device once a day and placebo to formoterol (placebo AEROLIZER® device) twice a day for 14 days. All participants were supplied with salbutamol/albuterol to use throughout the study as rescue medication.

Drug: indacaterol; Drug: placebo to formoterol; Drug: short acting β2- agonist

formoterol

ACTIVE COMPARATOR

Formoterol 12 μg delivered by the AEROLIZER® device twice a day and placebo to indacaterol (placebo TWISTHALER® device) once a day for 14 days. All participants were supplied with salbutamol/albuterol to use throughout the study as rescue medication.

Drug: formoterol; Drug: placebo to indacaterol; Drug: short acting β2- agonist

placebo

PLACEBO COMPARATOR

Placebo to indacaterol (placebo TWISTHALER® device) once a day and placebo to formoterol (placebo AEROLIZER® device) twice a day for 14 days. All participants were supplied with salbutamol/albuterol to use throughout the study as rescue medication.

Drug: placebo to indacaterol; Drug: placebo to formoterol; Drug: short acting β2- agonist

Interventions

indacaterol DRUG

Indacaterol delivered by multiple dose dry powder inhaler (TWISTHALER® device).

Indacaterol 250 μg; indacaterol 125 μg; indacaterol 500 μg; indacaterol 62.5 μg

formoterol DRUG

Formoterol delivered by oral inhalation via AEROLIZER® inhalation device.

formoterol

placebo to indacaterol DRUG

Placebo TWISTHALER® device

formoterol; placebo

placebo to formoterol DRUG

Placebo AEROLIZER® device

Indacaterol 250 μg; indacaterol 125 μg; indacaterol 500 μg; indacaterol 62.5 μg; placebo

short acting β2- agonist DRUG

100 μg / 90 μg salbutamol/albuterol Metered Dose Inhaler (MDI) or equivalent dose of Dry Powder Inhaler (DPI).

Indacaterol 250 μg; formoterol; indacaterol 125 μg; indacaterol 500 μg; indacaterol 62.5 μg; placebo

Eligibility Criteria

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

You may qualify if:

• Male and female adults aged ≥ 40 years, who have signed an Informed Consent Form prior to initiation of any study-related procedure (which include any adjustment to their current COPD treatment)
• Cooperative outpatients with a diagnosis of COPD (moderate to severe as classified by the Global Initiative for Obstructive Lung Disease (GOLD) Guidelines, 2006) and:
• Smoking history of at least 10 pack years
• Post-bronchodilator Forced Expiratory Volume in one second (FEV1) \< 80% and ≥30% of the predicted normal value.
• Post-bronchodilator FEV1/Forced vital capacity (FVC) \< 70%

You may not qualify if:

• Pregnant women, nursing mothers, or females of childbearing potential, regardless of whether or not sexually active, if they are not using acceptable methods of contraception.
• Patients who have been hospitalized for an exacerbation of their airways disease within 6 weeks prior to Visit 1 or between Visit 1 and Visit 2.
• Patients with a history of asthma.
• Patients with an acute respiratory tract infection within 4 weeks prior to Visit 1, will be not allowed to enter the study.
• Other clinically significant conditions which may interfere with the study conduct or patient safety as specified in the protocol.

Sponsors & Collaborators

• Novartis: lead
• Schering-Plough: collaborator

Study Sites (75)

Novartis Investigator site

Buenos Aires, Argentina

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Rosario, Argentina

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Santillán, Argentina

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Liège, Belgium

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Santiago, Chile

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Val Pariso, Chile

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Bois-Guillaume, France

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Clermot Ferand, France

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Lille, France

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Marseille, France

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Nantes, France

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Toulouse, France

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Berlin, Germany

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Bibertal, Germany

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Bochum, Germany

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Novartis Investigator Site - 2 sites

Bonn, Germany

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Cologne, Germany

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Frankfurt, Germany

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Hamburg, Germany

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Heidelberg, Germany

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Koblenz, Germany

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Marburg, Germany

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Solingen, Germany

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Budapest, Hungary

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Debrecen, Hungary

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Pécs, Hungary

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Dublin, Ireland

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Genova, Italy

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Napoli, Italy

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Pordenone, Italy

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Daugavpils, Latvia

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Riga, Latvia

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Kaunas, Lithuania

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Klaipėda, Lithuania

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Vilnius, Lithuania

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Tronheim, Norway

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Lima, Peru

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Izabelin, Poland

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Lodz, Poland

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Lublin, Poland

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Mrozy, Poland

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Olsztyn, Poland

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Rzeszów, Poland

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Wejhrowo, Poland

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Włocławek, Poland

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Bucharest, Romania

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Cluj-Napoca, Romania

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Iași, Romania

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Timișoara, Romania

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Bloemfontain, South Africa

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Bloemfontein, South Africa

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Cape Town, South Africa

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Durban, South Africa

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eManzimtoti, South Africa

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George, South Africa

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Johannesburg, South Africa

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Port Elizabeth, South Africa

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Pretoria, South Africa

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Tygerberg, South Africa

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Erzurum, Turkey (Türkiye)

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Isparta, Turkey (Türkiye)

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Istanbul, Turkey (Türkiye)

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Kahramanmaraş, Turkey (Türkiye)

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Kayseri, Turkey (Türkiye)

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Malatya, Turkey (Türkiye)

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Manisa, Turkey (Türkiye)

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Sanliurfa, Turkey (Türkiye)

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Trabzon, Turkey (Türkiye)

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Belfast, United Kingdom

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Chesterfield, United Kingdom

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Glasgow, United Kingdom

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Plymouth, United Kingdom

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Warminster, United Kingdom

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Watford, United Kingdom

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Whitstable, United Kingdom

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MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

indacaterol; Formoterol Fumarate

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)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

862-778-8300

Study Officials

• Novartis Pharma AG

  Novartis Pharmaceuticals

  STUDY CHAIR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• 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: November 13, 2007
• First Posted: November 14, 2007
• Study Start: October 1, 2007
• Primary Completion: May 1, 2008
• Study Completion: May 1, 2008
• Last Updated: January 18, 2013
• Results First Posted: January 18, 2013

Record last verified: 2012-11

Locations

FR (6); CL (2); AR (3); TU (9); PE (1); GB (7); IT (3); NO (1); DE (11); LA (2); IE (1); ZA (10); LI (3); HU (3); PL (8); RO (4); BE (1)