Clinical trial NCT00393458: Efficacy, Safety, and Tolerability of Once Daily Indacaterol in Chronic Obstructive Pulmonary Disease (COPD) Using Formoterol Twice Daily as Active Control
Official title: A 52-week Treatment, Multicenter, Randomized, Double-blind, Double-dummy, Placebo-controlled, Parallel-group Study to Assess the Efficacy, Safety, and Tolerability of Indacaterol (300 and 600 µg Once Daily) in Patients With Chronic Obstructive Pulmonary Disease, Using Formoterol (12 µg Twice Daily) as an Active Control
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Obstructive Pulmonary Disease
Keywords: chronic obstructive pulmonary disease
COPD
indacaterol
long-acting β2 agonist
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2006-10-27
Enrollment: 1732
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study was designed to assess the efficacy and long-term safety of 300 and 600 µg doses of indacaterol when delivered via a single-dose dry-powder inhaler (SDDPI) in patients with chronic obstructive pulmonary disease (COPD). Patients were randomized to receive either indacaterol 300 µg once daily, indacaterol 600 µg once daily, formoterol 12 µg twice daily, or placebo.


Eligibility criteria: Inclusion Criteria:

* Male and female adults ≥ 40 years, with a diagnosis of chronic obstructive pulmonary disease (COPD) according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines 2005 and:

  1. Smoking history of at least 20 pack years
  2. Post-bronchodilator forced expiratory volume in 1 second (FEV1) \< 80% and ≥ 30% of the predicted normal value
  3. Post-bronchodilator FEV1/FVC (forced volume capacity) \< 70% (Post refers to within 30 minutes after inhalation of 400 μg of salbutamol)

     Exclusion Criteria:
* Patients who were hospitalized for a COPD exacerbation in the 6 weeks prior to screening.
* Patients who 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 co-morbid conditions.

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

Primary outcomes:
measure: Trough Forced Expiratory Volume in 1 Second (FEV1) at Week 12 + 1 Day, Day 85
timeFrame: Week 12 + 1 day, Day 85
Secondary outcomes:
measure: Percentage of Days of Poor Control During 52 Weeks of Treatment
timeFrame: Baseline to end of study (Week 52)
Other outcomes:
Locations:
city: Buenos Aires
country: Argentina
facility: Novartis Investigator Site
city: Buenos Aires
country: Argentina
facility: Novartis
city: Mendoza
country: Argentina
facility: Novartis Investigator Site
city: San Miguel
country: Argentina
facility: Novartis Investigator Site
city: Santa Fe
country: Argentina
facility: Novartis Investigator Site
city: Rancagua
country: Chile
facility: Novartis Investigator Site
city: Santiago
country: Chile
facility: Novartis
city: Vina del Mar
country: Chile
facility: Novartis Investigator Site
city: Barranquilla
country: Colombia
facility: Novartis Investigator Site
city: Bogota
country: Colombia
facility: Novartis
city: Medellin
country: Colombia
facility: Novartis Investigator Site
city: Cvikov
country: Czech Republic
facility: Novartis Investigator Site
city: Kyjov
country: Czech Republic
facility: Novartis Investigator Site
city: Ostrava Poruba
country: Czech Republic
facility: Novartis Investigator Site
city: Pardubice
country: Czech Republic
facility: Novartis Investigator Site
city: Praha
country: Czech Republic
facility: Novartis
city: Tabor
country: Czech Republic
facility: Novartis Investigator Site
city: Zatec
country: Czech Republic
facility: Novartis Investigator Site
city: Aarhus
country: Denmark
facility: Novartis Investigator Site
city: Copenhagen
country: Denmark
facility: Novartis
city: Hellerup
country: Denmark
facility: Novartis Investigator Site
city: Hvidovre
country: Denmark
facility: Novartis Investigator Site
city: Molleparkvej
country: Denmark
facility: Novartis Investigator Site
city: Odense
country: Denmark
facility: Novartis Investigator Site
city: Guayaquil
country: Ecuador
facility: Novartis Investigator Site
city: Quito
country: Ecuador
facility: Novartis Investigator Site
city: Quito
country: Ecuador
facility: Novartis
city: Alexandria
country: Egypt
facility: Novartis Investigator Site
city: Assiut
country: Egypt
facility: Novartis Investigator Site
city: Cairo
country: Egypt
facility: Novartis Investigator Site
city: Cairo
country: Egypt
facility: Novartis
city: Tallinn
country: Estonia
facility: Novartis Investigator Site
city: Tartu
country: Estonia
facility: Novartis
city: Beuvry
country: France
facility: Novartis Investigator Site
city: Chamalieres
country: France
facility: Novartis Investigator Site
city: Ferolles-Attilly
country: France
facility: Novartis Investigator Site
city: Grasse
country: France
facility: Novartis Investigator Site
city: Marseilles
country: France
facility: Novartis Investigator Site
city: Montpellier Cedex
country: France
facility: Novartis Investigator Site
city: Nice
country: France
facility: Novartis Investigator Site
city: Nimes
country: France
facility: Novartis Investigator Site
city: Paris
country: France
facility: Novartis Investigator Site
city: Perpignan
country: France
facility: Novartis Investigator Site
city: Pessac Cedex
country: France
facility: Novartis Investigator Site
city: Strasbourg
country: France
facility: Novartis Investigator Site
city: Augsburg
country: Germany
facility: Novartis Investigator Site
city: Bad Segeberg
country: Germany
facility: Novartis Investigator Site
city: Bad Worishofen
country: Germany
facility: Novartis Investigator Site
city: Berlin
country: Germany
facility: Novartis Investigator Site
city: Bielefeld
country: Germany
facility: Novartis Investigator Site
city: Bochum
country: Germany
facility: Novartis Investigator Site
city: Bonn
country: Germany
facility: Novartis Investigator Site
city: Borstel
country: Germany
facility: Novartis Investigator Site
city: Darmstadt
country: Germany
facility: Novartis Investigator Site
city: Dortmund
country: Germany
facility: Novartis Investigator Site
city: Erfurt
country: Germany
facility: Novartis Investigator Site
city: Forchheim
country: Germany
facility: Novartis Investigator Site
city: Frankfurt
country: Germany
facility: Novartis Investigator Site
city: Gauting
country: Germany
facility: Novartis Investigator Site
city: Geesthacht
country: Germany
facility: Novartis Investigator Site
city: Gelsenkirchen
country: Germany
facility: Novartis Investigator Site
city: Grosshansdorf
country: Germany
facility: Novartis Investigator Site
city: Gummersbach
country: Germany
facility: Novartis Investigator Site
city: Hagen
country: Germany
facility: Novartis Investigator Site
city: Hamburg
country: Germany
facility: Novartis Investigator Site
city: Hannover
country: Germany
facility: Novartis Investigator Site
city: Ilvesheim
country: Germany
facility: Novartis Investigator Site
city: Kassel
country: Germany
facility: Novartis Investigator Site
city: Kiel
country: Germany
facility: Novartis Investigator Site
city: Leipzig
country: Germany
facility: Novartis Investigator Site
city: Luebeck
country: Germany
facility: Novartis Investigator Site
city: Luedenscheid
country: Germany
facility: Novartis Investigator Site
city: Mainz
country: Germany
facility: Novartis Investigator Site
city: Marburg
country: Germany
facility: Novartis Investigator Site
city: Muenchen
country: Germany
facility: Novartis Investigator Site
city: Neumunster
country: Germany
facility: Novartis Investigator Site
city: Nürnberg
country: Germany
facility: Novartis
city: Oschersleben
country: Germany
facility: Novartis Investigator Site
city: Ruedersdorf
country: Germany
facility: Novartis Investigator Site
city: Schoenefeld
country: Germany
facility: Novartis Investigator Site
city: Strausberg
country: Germany
facility: Novartis Investigator Site
city: Witten
country: Germany
facility: Novartis Investigator Site
city: Wuppertal
country: Germany
facility: Novartis Investigator Site
city: Budapest
country: Hungary
facility: Novartis Investigator Site
city: Budapest
country: Hungary
facility: Novartis
city: Deszk
country: Hungary
facility: Novartis Investigator Site
city: Matrahaza
country: Hungary
facility: Novartis Investigator Site
city: Mosdos
country: Hungary
facility: Novartis Investigator Site
city: Sopron
country: Hungary
facility: Novartis Investigator Site
city: Jerusalem
country: Israel
facility: Novartis Investigator Site
city: Petach-Tikva
country: Israel
facility: Novartis
city: Rehovot
country: Israel
facility: Novartis Investigator Site
city: Tel-Hashomer
country: Israel
facility: Novartis Investigator Site
city: Ancona
country: Italy
facility: Novartis Investigator Site
city: Catania
country: Italy
facility: Novartis Investigator Site
city: Ferrara
country: Italy
facility: Novartis Investigator Site
city: Firenze
country: Italy
facility: Novartis Investigator Site
city: Foggia
country: Italy
facility: Novartis Investigator Site
city: Genova
country: Italy
facility: Novartis Investigator Site
city: Milano
country: Italy
facility: Novartis Investigator Site
city: Milano
country: Italy
facility: Novartis
city: Pisa
country: Italy
facility: Novartis Investigator Site
city: Roma
country: Italy
facility: Novartis Investigator Site
city: Siena
country: Italy
facility: Novartis Investigator Site
city: Kyunggi
country: Korea, Republic of
facility: Novartis Investigator Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigator Site
city: Seoul
country: Korea, Republic of
facility: Novartis
city: Suwon
country: Korea, Republic of
facility: Novartis Investigator Site
city: Uijeongbu-si
country: Korea, Republic of
facility: Novartis Investigator Site
city: Daugavpils
country: Latvia
facility: Novartis Investigator Site
city: Jekabpils
country: Latvia
facility: Novartis Investigator Site
city: Riga
country: Latvia
facility: Novartis Investigator Site
city: Riga
country: Latvia
facility: Novartis
city: Alytus
country: Lithuania
facility: Novartis Investigator Site
city: Kaunas
country: Lithuania
facility: Novartis Investigator Site
city: Kaunas
country: Lithuania
facility: Novartis
city: Klaipeda
country: Lithuania
facility: Novartis Investigator Site
city: Vilnius
country: Lithuania
facility: Novartis Investigator Site
city: Almelo
country: Netherlands
facility: Novartis Investigator Site
city: Amersfoort
country: Netherlands
facility: Novartis Investigator Site
city: Arnhem
country: Netherlands
facility: Novartis
city: Breda
country: Netherlands
facility: Novartis Investigator Site
city: Ede
country: Netherlands
facility: Novartis Investigator Site
city: Eindhoven
country: Netherlands
facility: Novartis Investigator Site
city: Harderwijk
country: Netherlands
facility: Novartis Investigator Site
city: Helmond
country: Netherlands
facility: Novartis Investigator Site
city: Hengelo
country: Netherlands
facility: Novartis Investigator Site
city: Hoorn
country: Netherlands
facility: Novartis Investigator Site
city: Leeuwarden
country: Netherlands
facility: Novartis Investigator Site
city: Rotterdam
country: Netherlands
facility: Novartis Investigator Site
city: Sneek
country: Netherlands
facility: Novartis Investigator Site
city: Veldhoven
country: Netherlands
facility: Novartis Investigator Site
city: Zutphen
country: Netherlands
facility: Novartis Investigator Site
city: Lima
country: Peru
facility: Novartis Investigator Site
city: Lima
country: Peru
facility: Novartis
city: Bucharest
country: Romania
facility: Novartis
city: Cluj-Napoca
country: Romania
facility: Novartis Investigator Site
city: Iasi
country: Romania
facility: Novartis Investigator Site
city: Timisoara
country: Romania
facility: Novartis Investigator Site
city: Kazan
country: Russian Federation
facility: Novartis Investigator Site
city: Moscow
country: Russian Federation
facility: Novartis Investigator Site
city: Moscow
country: Russian Federation
facility: Novartis
city: Samara
country: Russian Federation
facility: Novartis Investigator Site
city: St Petersburg
country: Russian Federation
facility: Novartis Investigator Site
city: Yekaterinburg
country: Russian Federation
facility: Novartis Investigator Site
city: Banska Bystrica
country: Slovakia
facility: Novartis Investigator Site
city: Bratislava
country: Slovakia
facility: Novartis Investigator Site
city: Bratislava
country: Slovakia
facility: Novartis
city: Kosice
country: Slovakia
facility: Novartis Investigator Site
city: Partizanske
country: Slovakia
facility: Novartis Investigator Site
city: Alicante
country: Spain
facility: Novartis Investigator Site
city: Barcelona
country: Spain
facility: Novartis Investigator Site
city: Barcelona
country: Spain
facility: Novartis
city: Begonte
country: Spain
facility: Novartis Investigator Site
city: Caceres
country: Spain
facility: Novartis Investigator Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Mataro
country: Spain
facility: Novartis Investigator Site
city: Petrel
country: Spain
facility: Novartis Investigator Site
city: Ponferrada
country: Spain
facility: Novartis Investigator Site
city: Terrassa
country: Spain
facility: Novartis Investigator Site
city: Valencia
country: Spain
facility: Novartis Investigator Site
city: Aarau
country: Switzerland
facility: Novartis Investigator Site
city: Basel
country: Switzerland
facility: Novartis Investigator Site
city: Locarno
country: Switzerland
facility: Novartis Investigator Site
city: Munchenstein
country: Switzerland
facility: Novartis Investigator Site
city: Zuerich
country: Switzerland
facility: Novartis Investigator Site
city: Ankara
country: Turkey
facility: Novartis Investigator Site
city: Bursa
country: Turkey
facility: Novartis Investigator Site
city: Istanbul
country: Turkey
facility: Novartis
city: Izmir
country: Turkey
facility: Novartis Investigator Site
city: Mersin
country: Turkey
facility: Novartis Investigator Site
city: Yenisehir
country: Turkey
facility: Novartis Investigator Site
city: Belfast
country: United Kingdom
facility: Novartis Investigator Site
city: Bexhill-on-Sea
country: United Kingdom
facility: Novartis Investigator Site
city: Blackpool
country: United Kingdom
facility: Novartis Investigator Site
city: Chertsey
country: United Kingdom
facility: Novartis Investigator Site
city: Glasgow
country: United Kingdom
facility: Novartis Investigator Site
city: Leicester
country: United Kingdom
facility: Novartis Investigator Site
city: London
country: United Kingdom
facility: Novartis Investigator Site
city: Manchester
country: United Kingdom
facility: Novartis Investigator Site
city: Newcastle-upon-Tyne
country: United Kingdom
facility: Novartis Investigator Site
city: Slough
country: United Kingdom
facility: Novartis Investigator Site
city: Swansea
country: United Kingdom
facility: Novartis Investigator Site
Study officials:
affiliation: Novartis
name: Novartis Investigator Site
role: PRINCIPAL_INVESTIGATOR
References:
citation: Jones PW, Donohue JF, Nedelman J, Pascoe S, Pinault G, Lassen C. Correlating changes in lung function with patient outcomes in chronic obstructive pulmonary disease: a pooled analysis. Respir Res. 2011 Dec 29;12(1):161. doi: 10.1186/1465-9921-12-161.
citation: Bleecker ER, Siler T, Owen R, Kramer B. Bronchodilator efficacy and safety of indacaterol 150 mug once daily in patients with COPD: an analysis of pooled data. Int J Chron Obstruct Pulmon Dis. 2011;6:431-8. doi: 10.2147/COPD.S21073. Epub 2011 Aug 18.
citation: Jones PW, Mahler DA, Gale R, Owen R, Kramer B. Profiling the effects of indacaterol on dyspnoea and health status in patients with COPD. Respir Med. 2011 Jun;105(6):892-9. doi: 10.1016/j.rmed.2011.02.013. Epub 2011 Mar 11.
citation: Worth H, Chung KF, Felser JM, Hu H, Rueegg P. Cardio- and cerebrovascular safety of indacaterol vs formoterol, salmeterol, tiotropium and placebo in COPD. Respir Med. 2011 Apr;105(4):571-9. doi: 10.1016/j.rmed.2010.11.027. Epub 2011 Jan 11.
citation: Dahl R, Chung KF, Buhl R, Magnussen H, Nonikov V, Jack D, Bleasdale P, Owen R, Higgins M, Kramer B; INVOLVE (INdacaterol: Value in COPD: Longer Term Validation of Efficacy and Safety) Study Investigators. Efficacy of a new once-daily long-acting inhaled beta2-agonist indacaterol versus twice-daily formoterol in COPD. Thorax. 2010 Jun;65(6):473-9. doi: 10.1136/thx.2009.125435.