Efficacy, Safety, and Tolerability of Once Daily Indacaterol in Chronic Obstructive Pulmonary Disease (COPD) Using Formoterol Twice Daily as Active Control

Chronic Obstructive Pulmonary Disease Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00393458
• Other study ID #: CQAB149B2334
• Status: Completed
• Phase: Phase 3
• First received: October 25, 2006
• Last updated: July 22, 2011
• Start date: October 2006
• Est. completion date: July 2008

Study information

• Verified date: July 2011
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia MedicaBelgium: Federal Agency for Medicinal Products and Health ProductsSwitzerland: Federal Office of Public HealthChile: Instituto de Salud Pública de ChileColombia: INVIMA Instituto Nacional de Vigilancia de Medicamentos y AlimentosCzech Republic: State Institute for Drug ControlGermany: Federal Institute for Drugs and Medical DevicesDenmark: Danish Medicines AgencyEcuador: Public Health MinistryEgypt: Ministry of Health and PopulationSpain: Spanish Agency of MedicinesEstonia: The State Agency of MedicineFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)United Kingdom: Medicines and Healthcare Products Regulatory AgencyHungary: National Institute of PharmacyIsrael: Ministry of HealthItaly: National Monitoring Centre for Clinical Trials - Ministry of HealthKorea: Food and Drug AdministrationLithuania: State Medicine Control Agency - Ministry of HealthLatvia: State Agency of MedicinesNetherlands: Medicines Evaluation Board (MEB)Peru: Ministry of HealthRomania: Ministry of Public HealthRussia: Ministry of Health of the Russian FederationSlovakia: State Institute for Drug ControlSweden: Medical Products AgencyTurkey: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1732
• Est. completion date: July 2008
• Est. primary completion date: July 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years and older

Eligibility

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.

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
• Lung Diseases
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• Indacaterol
Indacaterol was supplied in powder-filled capsules with a single-dose dry-powder inhaler (SDDPI).
• Formoterol
Formoterol was supplied in powder-filled capsules with the manufacturer's proprietary inhalation device (Aerolizer®).
• Placebo to indacaterol
Placebo to indacaterol was supplied in powder-filled capsules with a single-dose dry-powder inhaler (SDDPI).
• Placebo to formoterol
Placebo to formoterol was supplied in powder-filled capsules with the manufacturer's proprietary inhalation device (Aerolizer®).

Locations

Country	Name	City	State
Argentina	Novartis	Buenos Aires
Argentina	Novartis Investigator Site	Buenos Aires
Argentina	Novartis Investigator Site	Mendoza
Argentina	Novartis Investigator Site	San Miguel
Argentina	Novartis Investigator Site	Santa Fe
Chile	Novartis Investigator Site	Rancagua
Chile	Novartis	Santiago
Chile	Novartis Investigator Site	Vina del Mar
Colombia	Novartis Investigator Site	Barranquilla
Colombia	Novartis	Bogota
Colombia	Novartis Investigator Site	Medellin
Czech Republic	Novartis Investigator Site	Cvikov
Czech Republic	Novartis Investigator Site	Kyjov
Czech Republic	Novartis Investigator Site	Ostrava Poruba
Czech Republic	Novartis Investigator Site	Pardubice
Czech Republic	Novartis	Praha
Czech Republic	Novartis Investigator Site	Tabor
Czech Republic	Novartis Investigator Site	Zatec
Denmark	Novartis Investigator Site	Aarhus
Denmark	Novartis	Copenhagen
Denmark	Novartis Investigator Site	Hellerup
Denmark	Novartis Investigator Site	Hvidovre
Denmark	Novartis Investigator Site	Molleparkvej
Denmark	Novartis Investigator Site	Odense
Ecuador	Novartis Investigator Site	Guayaquil
Ecuador	Novartis	Quito
Ecuador	Novartis Investigator Site	Quito
Egypt	Novartis Investigator Site	Alexandria
Egypt	Novartis Investigator Site	Assiut
Egypt	Novartis	Cairo
Egypt	Novartis Investigator Site	Cairo
Estonia	Novartis Investigator Site	Tallinn
Estonia	Novartis	Tartu
France	Novartis Investigator Site	Beuvry
France	Novartis Investigator Site	Chamalieres
France	Novartis Investigator Site	Ferolles-Attilly
France	Novartis Investigator Site	Grasse
France	Novartis Investigator Site	Marseilles
France	Novartis Investigator Site	Montpellier Cedex
France	Novartis Investigator Site	Nice
France	Novartis Investigator Site	Nimes
France	Novartis Investigator Site	Paris
France	Novartis Investigator Site	Perpignan
France	Novartis Investigator Site	Pessac Cedex
France	Novartis Investigator Site	Strasbourg
Germany	Novartis Investigator Site	Augsburg
Germany	Novartis Investigator Site	Bad Segeberg
Germany	Novartis Investigator Site	Bad Worishofen
Germany	Novartis Investigator Site	Berlin
Germany	Novartis Investigator Site	Bielefeld
Germany	Novartis Investigator Site	Bochum
Germany	Novartis Investigator Site	Bonn
Germany	Novartis Investigator Site	Borstel
Germany	Novartis Investigator Site	Darmstadt
Germany	Novartis Investigator Site	Dortmund
Germany	Novartis Investigator Site	Erfurt
Germany	Novartis Investigator Site	Forchheim
Germany	Novartis Investigator Site	Frankfurt
Germany	Novartis Investigator Site	Gauting
Germany	Novartis Investigator Site	Geesthacht
Germany	Novartis Investigator Site	Gelsenkirchen
Germany	Novartis Investigator Site	Grosshansdorf
Germany	Novartis Investigator Site	Gummersbach
Germany	Novartis Investigator Site	Hagen
Germany	Novartis Investigator Site	Hamburg
Germany	Novartis Investigator Site	Hannover
Germany	Novartis Investigator Site	Ilvesheim
Germany	Novartis Investigator Site	Kassel
Germany	Novartis Investigator Site	Kiel
Germany	Novartis Investigator Site	Leipzig
Germany	Novartis Investigator Site	Luebeck
Germany	Novartis Investigator Site	Luedenscheid
Germany	Novartis Investigator Site	Mainz
Germany	Novartis Investigator Site	Marburg
Germany	Novartis Investigator Site	Muenchen
Germany	Novartis Investigator Site	Neumunster
Germany	Novartis	Nürnberg
Germany	Novartis Investigator Site	Oschersleben
Germany	Novartis Investigator Site	Ruedersdorf
Germany	Novartis Investigator Site	Schoenefeld
Germany	Novartis Investigator Site	Strausberg
Germany	Novartis Investigator Site	Witten
Germany	Novartis Investigator Site	Wuppertal
Hungary	Novartis	Budapest
Hungary	Novartis Investigator Site	Budapest
Hungary	Novartis Investigator Site	Deszk
Hungary	Novartis Investigator Site	Matrahaza
Hungary	Novartis Investigator Site	Mosdos
Hungary	Novartis Investigator Site	Sopron
Israel	Novartis Investigator Site	Jerusalem
Israel	Novartis	Petach-Tikva
Israel	Novartis Investigator Site	Rehovot
Israel	Novartis Investigator Site	Tel-Hashomer
Italy	Novartis Investigator Site	Ancona
Italy	Novartis Investigator Site	Catania
Italy	Novartis Investigator Site	Ferrara
Italy	Novartis Investigator Site	Firenze
Italy	Novartis Investigator Site	Foggia
Italy	Novartis Investigator Site	Genova
Italy	Novartis	Milano
Italy	Novartis Investigator Site	Milano
Italy	Novartis Investigator Site	Pisa
Italy	Novartis Investigator Site	Roma
Italy	Novartis Investigator Site	Siena
Korea, Republic of	Novartis Investigator Site	Kyunggi
Korea, Republic of	Novartis	Seoul
Korea, Republic of	Novartis Investigator Site	Seoul
Korea, Republic of	Novartis Investigator Site	Suwon
Korea, Republic of	Novartis Investigator Site	Uijeongbu-si
Latvia	Novartis Investigator Site	Daugavpils
Latvia	Novartis Investigator Site	Jekabpils
Latvia	Novartis	Riga
Latvia	Novartis Investigator Site	Riga
Lithuania	Novartis Investigator Site	Alytus
Lithuania	Novartis	Kaunas
Lithuania	Novartis Investigator Site	Kaunas
Lithuania	Novartis Investigator Site	Klaipeda
Lithuania	Novartis Investigator Site	Vilnius
Netherlands	Novartis Investigator Site	Almelo
Netherlands	Novartis Investigator Site	Amersfoort
Netherlands	Novartis	Arnhem
Netherlands	Novartis Investigator Site	Breda
Netherlands	Novartis Investigator Site	Ede
Netherlands	Novartis Investigator Site	Eindhoven
Netherlands	Novartis Investigator Site	Harderwijk
Netherlands	Novartis Investigator Site	Helmond
Netherlands	Novartis Investigator Site	Hengelo
Netherlands	Novartis Investigator Site	Hoorn
Netherlands	Novartis Investigator Site	Leeuwarden
Netherlands	Novartis Investigator Site	Rotterdam
Netherlands	Novartis Investigator Site	Sneek
Netherlands	Novartis Investigator Site	Veldhoven
Netherlands	Novartis Investigator Site	Zutphen
Peru	Novartis	Lima
Peru	Novartis Investigator Site	Lima
Romania	Novartis	Bucharest
Romania	Novartis Investigator Site	Cluj-Napoca
Romania	Novartis Investigator Site	Iasi
Romania	Novartis Investigator Site	Timisoara
Russian Federation	Novartis Investigator Site	Kazan
Russian Federation	Novartis	Moscow
Russian Federation	Novartis Investigator Site	Moscow
Russian Federation	Novartis Investigator Site	Samara
Russian Federation	Novartis Investigator Site	St Petersburg
Russian Federation	Novartis Investigator Site	Yekaterinburg
Slovakia	Novartis Investigator Site	Banska Bystrica
Slovakia	Novartis	Bratislava
Slovakia	Novartis Investigator Site	Bratislava
Slovakia	Novartis Investigator Site	Kosice
Slovakia	Novartis Investigator Site	Partizanske
Spain	Novartis Investigator Site	Alicante
Spain	Novartis	Barcelona
Spain	Novartis Investigator Site	Barcelona
Spain	Novartis Investigator Site	Begonte
Spain	Novartis Investigator Site	Caceres
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigator Site	Mataro
Spain	Novartis Investigator Site	Petrel
Spain	Novartis Investigator Site	Ponferrada
Spain	Novartis Investigator Site	Terrassa
Spain	Novartis Investigator Site	Valencia
Switzerland	Novartis Investigator Site	Aarau
Switzerland	Novartis Investigator Site	Basel
Switzerland	Novartis Investigator Site	Locarno
Switzerland	Novartis Investigator Site	Munchenstein
Switzerland	Novartis Investigator Site	Zuerich
Turkey	Novartis Investigator Site	Ankara
Turkey	Novartis Investigator Site	Bursa
Turkey	Novartis	Istanbul
Turkey	Novartis Investigator Site	Izmir
Turkey	Novartis Investigator Site	Mersin
Turkey	Novartis Investigator Site	Yenisehir
United Kingdom	Novartis Investigator Site	Belfast
United Kingdom	Novartis Investigator Site	Bexhill-on-Sea
United Kingdom	Novartis Investigator Site	Blackpool
United Kingdom	Novartis Investigator Site	Chertsey
United Kingdom	Novartis Investigator Site	Glasgow
United Kingdom	Novartis Investigator Site	Leicester
United Kingdom	Novartis Investigator Site	London
United Kingdom	Novartis Investigator Site	Manchester
United Kingdom	Novartis Investigator Site	Newcastle-upon-Tyne
United Kingdom	Novartis Investigator Site	Slough
United Kingdom	Novartis Investigator Site	Swansea

Sponsors (1)

Lead Sponsor	Collaborator
Novartis

Countries where clinical trial is conducted

Argentina,  Chile,  Colombia,  Czech Republic,  Denmark,  Ecuador,  Egypt,  Estonia,  France,  Germany,  Hungary,  Israel,  Italy,  Korea, Republic of,  Latvia,  Lithuania,  Netherlands,  Peru,  Romania,  Russian Federation,  Slovakia,  Spain,  Switzerland,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Trough Forced Expiratory Volume in 1 Second (FEV1) at 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 treatment. The analysis included baseline FEV1, FEV1 pre-dose and 30 minutes post-dose of salbutamol/albuterol during screening, and FEV1 pre-dose and 1 hour post-dose of ipratropium during screening as covariates.	Week 12 + 1 day, Day 85	No
Secondary	Percentage of Days of Poor Control During 52 Weeks of Treatment	Percentage of days of poor control was defined as the number of days in the patient diary with a score = 2 (scale of 0-3, a higher number means more severe symptoms) for at least 2 of 5 symptoms (cough, wheeze, production of sputum, color of sputum, breathlessness) over 52 weeks divided by the number of evaluable days (days with = 2 symptoms with scores). The analysis included baseline percentage of days of poor control, FEV1 pre-dose and 30 minutes post-dose of salbutamol/albuterol during screening, and FEV1 pre-dose and 1 hour post-dose of ipratropium during screening as covariates.	Baseline to end of study (Week 52)	No