Effect of Roflumilast in Chronic Obstructive Pulmonary Disease (COPD) Patients Treated With Tiotropium: The HELIOS Study (BY217/M2-128)

Chronic Obstructive Pulmonary Disease Clinical Trial

— HELIOS  

Official title:

Effect of Roflumilast in COPD Patients Treated With Tiotropium. A 24-week, Double-blind Study With 500 µg Roflumilast Once Daily Versus Placebo. The HELIOS Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00424268
• Other study ID #: BY217/M2-128
• Secondary ID: 2006-004508-37
• Status: Completed
• Phase: Phase 3
• First received: January 18, 2007
• Last updated: May 4, 2012
• Start date: January 2007
• Est. completion date: July 2008

Study information

• Verified date: August 2011
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Health authority: Austria: Federal Office for Safety in Health CareFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Germany: Federal Institute for Drugs and Medical DevicesHungary: National Institute of PharmacyItaly: The Italian Medicines AgencySpain: Spanish Agency of MedicinesUnited Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial Summary

The aim of the study is to compare the efficacy of roflumilast to placebo on pulmonary function and symptomatic parameters in patients with chronic obstructive pulmonary disease (COPD) during concomitant administration of tiotropium. The study duration will last up to 28 weeks. The study will provide further data on safety and tolerability of roflumilast.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 743
• Est. completion date: July 2008
• Est. primary completion date: January 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years and older

Eligibility

Main Inclusion Criteria:

• History of COPD for at least 12 months prior to baseline visit and chronic productive cough for 3 months in each of the 2 years prior to baseline visit

• FEV1/FVC ratio (post-bronchodilator) = 70%

• FEV1 (post-bronchodilator) between = 40% and = 70% of predicted

• Treated with tiotropium for at least 3 months before enrollment

• At least 28 puffs of rescue medication during last week prior to randomization

Main Exclusion Criteria:

• COPD exacerbation indicated by a treatment with systemic glucocorticosteroids and/or antibiotics not stopped at least 4 weeks prior to baseline visit

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

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

Intervention

Drug:
• Roflumilast
500 µg, once daily, oral administration in the morning
• Placebo
once daily

Locations

Country	Name	City	State
Austria	Altana Pharma/Nycomed Investigational Site	Feldbach
Austria	Altana Pharma/Nycomed Investigational Site	Gänserndorf
Austria	Altana Pharma/Nycomed Investigational Site	Hallein
Austria	Altana Pharma/Nycomed Investigational Site	Linz
Austria	Altana Pharma/Nycomed Investigational Site	Spittal an der Drau
France	Altana Pharma/Nycomed Investigational Site	Beuvry
France	Altana Pharma/Nycomed Investigational Site	Chauny Cedex
France	Altana Pharma/Nycomed Investigational Site	Grasse
France	Altana Pharma/Nycomed Investigational Site	Lyon
France	Altana Pharma/Nycomed Investigational Site	Martigues Cedex
France	Altana Pharma/Nycomed Investigational Site	Montigny-Les-Metz
France	Altana Pharma/Nycomed Investigational Site	Nantes
France	Altana Pharma/Nycomed Investigational Site	Nice
France	Altana Pharma/Nycomed Investigational Site	Nimes
France	Altana Pharma/Nycomed Investigational Site	Nimes Cedex 9
France	Altana Pharma/Nycomed Investigational Site	Ollioules
France	Altana Pharma/Nycomed Investigational Site	Perpignan Cedex
France	Altana Pharma/Nycomed Investigational Site	Saint Laurent Du Var
France	Altana Pharma/Nycomed Investigational Site	Saint-Quentin
France	Altana Pharma/Nycomed Investigational Site	Toulon
Germany	Altana Pharma/Nycomed Investigational Site	Bad Homburg
Germany	Altana Pharma/Nycomed Investigational Site	Dortmund
Germany	Altana Pharma/Nycomed Investigational Site	Geesthacht
Germany	Altana Pharma/Nycomed Investigational Site	Gelnhausen
Germany	Altana Pharma/Nycomed Investigational Site	Göppingen
Germany	Altana Pharma/Nycomed Investigational Site	Hannover
Germany	Altana Pharma/Nycomed Investigational Site	Koblenz
Germany	Altana Pharma/Nycomed Investigational Site	Landsberg/Lech
Germany	Altana Pharma/Nycomed Investigational Site	Leonberg
Germany	Altana Pharma/Nycomed Investigational Site	Marburg
Germany	Altana Pharma/Nycomed Investigational Site	Saarbrücken
Germany	Altana Pharma/Nycomed Investigational Site	Saarlouis
Germany	Altana Pharma/Nycomed Investigational Site	Schwetzingen
Germany	Altana Pharma/Nycomed Investigational Site	Sinsheim
Germany	Altana Pharma/Nycomed Investigational Site	Weyhe
Germany	Altana Pharma/Nycomed Investigational Site	Witten
Hungary	Altana Pharma/Nycomed Investigational Site	Budapest
Hungary	Altana Pharma/Nycomed Investigational Site	Budapest
Hungary	Altana Pharma/Nycomed Investigational Site	Budapest
Hungary	Altana Pharma/Nycomed Investigational Site	Cegled
Hungary	Altana Pharma/Nycomed Investigational Site	Csorna
Hungary	Altana Pharma/Nycomed Investigational Site	Erd
Hungary	Altana Pharma/Nycomed Investigational Site	Györ
Hungary	Altana Pharma/Nycomed Investigational Site	Hódmezovásárhely
Hungary	Altana Pharma/Nycomed Investigational Site	Matrahaza
Hungary	Altana Pharma/Nycomed Investigational Site	Nyiregyháza
Hungary	Altana Pharma/Nycomed Investigational Site	Szentes
Hungary	Altana Pharma/Nycomed Investigational Site	Szolnok
Italy	Altana Pharma/Nycomed Investigational Site	Bassano Del Grappa (VI)
Italy	Altana Pharma/Nycomed Investigational Site	Cisanello (PI)
Italy	Altana Pharma/Nycomed Investigational Site	Foggia
Italy	Altana Pharma/Nycomed Investigational Site	Genova
Italy	Altana Pharma/Nycomed Investigational Site	Milano
Italy	Altana Pharma/Nycomed Investigational Site	Modena
Italy	Altana Pharma/Nycomed Investigational Site	Pavullo nel Frignano (MO)
Italy	Altana Pharma/Nycomed Investigational Site	Pordenone
Italy	Altana Pharma/Nycomed Investigational Site	Reggio Emilia
Italy	Altana Pharma/Nycomed Investigational Site	Verona
Spain	Altana Pharma/Nycomed Investigational Site	Alicante
Spain	Altana Pharma/Nycomed Investigational Site	Baracaldo (Vizcaya)
Spain	Altana Pharma/Nycomed Investigational Site	Candia
Spain	Altana Pharma/Nycomed Investigational Site	Escaldes-Engordany
Spain	Altana Pharma/Nycomed Investigational Site	Galdakao
Spain	Altana Pharma/Nycomed Investigational Site	Guadalajara
Spain	Altana Pharma/Nycomed Investigational Site	Jerez de la Frontera
Spain	Altana Pharma/Nycomed Investigational Site	La Coruna
Spain	Altana Pharma/Nycomed Investigational Site	Lleida
Spain	Altana Pharma/Nycomed Investigational Site	Lugo
Spain	Altana Pharma/Nycomed Investigational Site	Madrid
Spain	Altana Pharma/Nycomed Investigational Site	Madrid
Spain	Altana Pharma/Nycomed Investigational Site	Madrid
Spain	Altana Pharma/Nycomed Investigational Site	Mostoles Madrid
Spain	Altana Pharma/Nycomed Investigational Site	Pozuelo de Alarcón
Spain	Altana Pharma/Nycomed Investigational Site	Requena
Spain	Altana Pharma/Nycomed Investigational Site	Sant Cugat del Valles
Spain	Altana Pharma/Nycomed Investigational Site	Santa Cruz de Tenerife
Spain	Altana Pharma/Nycomed Investigational Site	Sevilla
Spain	Altana Pharma/Nycomed Investigational Site	Valencia
Spain	Altana Pharma/Nycomed Investigational Site	Valencia
Spain	Altana Pharma/Nycomed Investigational Site	Valencia
Spain	Altana Pharma/Nycomed Investigational Site	Valencia
United Kingdom	Altana Pharma/Nycomed Investigational Site	Ashford
United Kingdom	Altana Pharma/Nycomed Investigational Site	Atherstone, Warwick
United Kingdom	Altana Pharma/Nycomed Investigational Site	Barry
United Kingdom	Altana Pharma/Nycomed Investigational Site	Bexhill-on-Sea, East Sussex
United Kingdom	Altana Pharma/Nycomed Investigational Site	Bolton
United Kingdom	Altana Pharma/Nycomed Investigational Site	Bolton Lancs
United Kingdom	Altana Pharma/Nycomed Investigational Site	Chesterfield
United Kingdom	Altana Pharma/Nycomed Investigational Site	Chesterfield Derbyshire
United Kingdom	Altana Pharma/Nycomed Investigational Site	Chippenham
United Kingdom	Altana Pharma/Nycomed Investigational Site	Co. Antrim
United Kingdom	Altana Pharma/Nycomed Investigational Site	Darlington, Co. Durham
United Kingdom	Altana Pharma/Nycomed Investigational Site	East Sussex
United Kingdom	Altana Pharma/Nycomed Investigational Site	Glasgow
United Kingdom	Altana Pharma/Nycomed Investigational Site	Harrow
United Kingdom	Altana Pharma/Nycomed Investigational Site	Keresely End, Coventry
United Kingdom	Altana Pharma/Nycomed Investigational Site	Plymouth
United Kingdom	Altana Pharma/Nycomed Investigational Site	Sheffield
United Kingdom	Altana Pharma/Nycomed Investigational Site	Solihull
United Kingdom	Altana Pharma/Nycomed Investigational Site	Swindon, Wilts
United Kingdom	Altana Pharma/Nycomed Investigational Site	Trowbridge
United Kingdom	Altana Pharma/Nycomed Investigational Site	Watford
United Kingdom	Altana Pharma/Nycomed Investigational Site	Yaxley

Sponsors (1)

Lead Sponsor	Collaborator
Takeda

Countries where clinical trial is conducted

Austria,  France,  Germany,  Hungary,  Italy,  Spain,  United Kingdom, 

References & Publications (1)

Fabbri LM, Calverley PM, Izquierdo-Alonso JL, Bundschuh DS, Brose M, Martinez FJ, Rabe KF; M2-127 and M2-128 study groups. Roflumilast in moderate-to-severe chronic obstructive pulmonary disease treated with longacting bronchodilators: two randomised clin — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pre-bronchodilator Forced Expiratory Volume in First Second (FEV1)	Mean change from baseline during the treatment period in pre-bronchodilator FEV1 [L]	Change from baseline over 24 weeks of treatment	No
Secondary	Post-bronchodilator FEV1	Mean change from baseline during the treatment period in post-bronchodilator FEV1 [L]	Change from baseline over 24 weeks of treatment	No
Secondary	COPD Exacerbation Rate (Moderate or Severe)	Mean rate of COPD exacerbations requiring oral or parenteral glucocorticosteroids (=moderate COPD exacerbations), or requiring hospitalization, or leading to death (=severe COPD exacerbations), per patient per year.; A COPD exacerbation is an event in the natural course of the disease characterized by a change in the patient's baseline dyspnea, cough and/or sputum beyond day-to-day variability sufficient to warrant a change in management [American Thoracic Society (ATS) / European Respiratory Society (ERS) 2005].	24 weeks treatment period	No
Secondary	Transition Dyspnea Index (TDI) Focal Score	The TDI is a recognized questionnaire to measure dyspnea in an out patient COPD population. At baseline, 3 components of dyspnea, each graded with 4 questions, were asked: Functional Impairment; Magnitude of Task; Magnitude of Effort; At each of the post-randomization visits questions from the TDI were asked related to 3 components: Change in; Functional Impairment; Magnitude of Task; Magnitude of Effort; Each question in the TDI is graded from -3 (major deterioration) to +3 (major improvement). This results in a TDI Focal Score ranging from -9 to +9.	Change from baseline over 24 weeks of treatment	No
Secondary	Shortness of Breath Questionnaire (SOBQ) Total Score	Mean change from baseline during the treatment period in SOBQ. This is a 24-item measure that assesses self-reported shortness of breath while performing a variety of activities of daily living.; The questions were administered at visits V0, V2, V3, V4, V5, V6 and Vend to assess the perceived shortness of breath of the patient.; For each activity listed in the questionnaire the patient should rate his/her breathlessness on a scale between zero and five, where zero is "not at all breathless" and five is "maximally breathless or too breathless to do the activity".	Change from baseline over 24 weeks of treatment	No