Long-term Efficacy and Safety of Aclidinium Bromide/Formoterol Fumarate Fixed-Dose Combination

Chronic Obstructive Pulmonary Disease (COPD) Clinical Trial

Official title:

Efficacy and Safety of Aclidinium Bromide/Formoterol Fumarate Fixed-dose Combinations Compared With Individual Components and Placebo When Administered to Patients With Stable Chronic Obstructive Pulmonary Disease.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01462942
• Other study ID #: M/40464/30
• Status: Completed
• Phase: Phase 3
• First received: October 26, 2011
• Last updated: June 9, 2016
• Start date: October 2011
• Est. completion date: January 2013

Study information

• Verified date: June 2016
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical DevicesSouth Korea: Korea Food and Drug Administration (KFDA)Netherlands: Medicines Evaluation Board (MEB)Belgium: Federal Agency for Medicinal Products and Health ProductsSweden: Institutional Review BoardAustria: EthikkommissionFinland: Finnish Medicines AgencyDenmark: Ethics CommitteeFrance: Institutional Ethical CommitteeCzech Republic: Ethics CommitteeHungary: Scientific and Medical Research Council Ethics CommitteeSpain: Agencia Española de Medicamentos y Productos SanitariosItaly: National Monitoring Centre for Clinical Trials - Ministry of HealthRussia: Ethics CommitteeSlovak Republic: Ethics CommitteeUkraine: Ethics CommitteeRomania: National Medicines AgencySouth Africa: Human Research Ethics CommitteeBulgaria: Bulgarian Drug AgencyUnited Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial Summary

The objective is to provide data supporting the use of LAS40464 as an efficacious and safe maintenance bronchodilator treatment of patients with Chronic Obstructive Pulmonary Disease (COPD).

Description:

This Phase III study seeks to confirm the long-term bronchodilator efficacy and effects on COPD related health status and other secondary parameters as well as the safety of two doses of the combination of aclidinium bromide/formoterol FDC (FDC 400/12 μg and 400/6 μg) compared with aclidinium bromide monotherapy 400 μg, formoterol monotherapy 12 μg and placebo.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1731
• Est. completion date: January 2013
• Est. primary completion date: December 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years and older

Eligibility

Inclusion Criteria:

• Adult male or non-pregnant, non-lactating female aged =40. Women of childbearing potential are allowed to enter the trial if they show to have a negative serum pregnancy test at the Screening Visit and are using, during the last two months before the Screening Visit, at least one medically approved and highly effective method of birth control defined as those which result in a low failure rate (i.e less than 1% per year) when used consistently and correctly such as implants, injectables, oral contraceptives combined with at least one barrier method, hormonal Intrauterine Devices (IUDs), sexual abstinence or vasectomy of the partner.

• Current or ex-cigarette smoker, with a smoking history of at least 10 pack-years.

• Patient with a clinical diagnosis of stable COPD according to the Global Initiative for Chronic Lung Disease "GOLD" Guidelines at the Screening Visit.

• Patient whose FEV1/FVC (Forced Vital Capacity) at the Screening Visit measured between 10-15 minutes post inhalation of 400 micrograms of salbutamol is < 70% (i.e., 100 x Post-salbutamol FEV1 /FVC < 70%).

• Patient with a diagnosis of moderate to severe COPD according to the GOLD Guidelines classification (stages II and III) at the Screening Visit: FEV1 measured between 10-15 minutes post inhalation of 400 micro grams of salbutamol is 30% < FEV1 < 80% of the predicted normal value (i.e., 100 x Post-salbutamol FEV1/ Predicted FEV1 must be < 80% and = 30%).

• Patient must be able to perform repeatable pulmonary function testing for FEV1 according to American Thoracic Society/European Respiratory Society "ATS/ERS" 2005 criteria at Screening Visit.

• Patient who is eligible and able to participate in the trial and who consent to do so in writing after the purpose and nature of the investigation have been explained.

Exclusion Criteria:

• History or current diagnosis of asthma.

• Any respiratory tract infection (including the upper respiratory tract) or COPD exacerbation in the 6 weeks before Screening Visit.

• Patient hospitalised for COPD exacerbation within 3 months prior to Screening Visit.

• Clinically significant respiratory conditions defined as: Known active tuberculosis.

• History of interstitial lung or massive pulmonary thromboembolic disease.

• Pulmonary resection or lung volume reduction surgery within 12 months prior to Screening Visit.

• History of lung transplantation.

• History of bronchiectasis secondary to respiratory diseases others than COPD (e.g., cystic fibrosis, Kartagener's syndrome, etc).

• Known a1-antitrypsin deficiency.

• Use of long-term oxygen therapy (= 15 hours/day).

• Clinically significant cardiovascular conditions changes in the pharmacological therapy or other intervention within 12 months prior to Screening Visit, or newly diagnosed arrhythmia within the previous 3 months prior to Screening Visit.

• Hospitalisation within 12 months prior to Screening Visit for heart failure functional classes III (marked limitation of activity and only comfortable at rest) and IV (need of complete rest, confinement to bed or chair, discomfort at any physical activity and presence of symptoms at rest) as per the New York Heart Association.

• Patient with interval corrected for heart rate "QTc" [calculated according to formulae (QTc=QT/RR1/2) > 470 msec as indicated in the centralised reading report assessed at Screening Visit.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Obstructive Pulmonary Disease (COPD)
• Lung Diseases
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• Aclidinium Bromide/Formoterol Fumarate
Inhaled Aclidinium/formoterol Fixed Dose Combination (FDC) low dose, twice per day
• Aclidinium Bromide/Formoterol Fumarate
Inhaled Aclidinium/formoterol FDC high dose, twice per day
• Aclidinium Bromide
Inhaled Aclidinium 400 µg, twice per day
• Placebo
Inhaled dose-matched placebo, twice per day
• Formoterol Fumarate
Inhaled Formoterol 12 µg, twice per day

Locations

Country	Name	City	State
Austria	Almirall Investigational Site #2	Graz
Austria	Almirall Investigational Site #3	Salzburg
Belgium	Almirall Investigational Site #3	Edegem
Belgium	Almirall Investigational Site #2	Genk
Bulgaria	Almirall Investigational Site #6	Ruse
Bulgaria	Almirall Investigational Site #10	Sevlievo
Bulgaria	Almirall Investigational Site #11	Sofia
Bulgaria	Almirall Investigational Site #2	Sofia
Bulgaria	Almirall Investigational Site #8	Sofia
Croatia	Almirall Investigational Site #2	Zagreb
Croatia	Almirall Investigational Site #4	Zagreb
Czech Republic	Almirall Investigational Site #8	Brno
Czech Republic	Almirall Investigational Site #3	Jindrichuv Hradec
Czech Republic	Almirall Investigational Site #10	Karlovy Vary
Czech Republic	Almirall Investigational Site #9	Liberec
Czech Republic	Almirall Investigational Site #16	Ostrava Hrabuvka
Czech Republic	Almirall Investigational Site #2	Praha 3
Czech Republic	Almirall Investigational Site #12	Praha 5
Czech Republic	Almirall Investigational Site #6	Praha 5 - Radotin
Czech Republic	Almirall Investigational Site #15	Praha 6
Czech Republic	Almirall Investigational Site #14	Praha 8
Czech Republic	Almirall Investigational Site #11	Strakonice
Czech Republic	Almirall Investigational Site #1	Tabor
Denmark	Almirall Investigational Site #4	Hillerød
Denmark	Almirall Investigational Site #1	København NV
Denmark	Almirall Investigational Site #5	Odense
Denmark	Almirall Investigational Site #2	Silkeborg
Finland	Almirall Investigational Site #7	Espoo
Finland	Almirall Investigational Site #8	Jyväskylä
Finland	Almirall Investigational Site #1	Tampere
Finland	Almirall Investigational Site #6	Tampere
Finland	Almirall Investigational Site #3	Turku
France	Almirall Investigational Site #6	Lille cedex
France	Almirall Investigational Site #10	Marseille cedex 6
France	Almirall Investigational Site #11	Montpellier cedex 5
France	Almirall Investigational Site #1	Pessac
France	Almirall Investigational Site #3	Rennes
France	Almirall Investigational Site #8	Toulouse
France	Almirall Investigational Site #12	Vieux Conde
Germany	Almirall Investigational Site #11	Berlin
Germany	Almirall Investigational Site #12	Berlin
Germany	Almirall Investigational Site #19	Berlin
Germany	Almirall Investigational Site #2	Berlin
Germany	Almirall Investigational Site #24	Berlin
Germany	Almirall Investigational Site #16	Bochum
Germany	Almirall Investigational Site #23	Bonn
Germany	Almirall Investigational Site #10	Dresden
Germany	Almirall Investigational Site #15	Dresden
Germany	Almirall Investigational Site #13	Frankfurt
Germany	Almirall Investigational Site #5	Frankfurt
Germany	Almirall Investigational Site #33	Haltern in Westfalen
Germany	Almirall Investigational Site #21	Hamburg
Germany	Almirall Investigational Site #7	Hamburg
Germany	Almirall Investigational Site #36	Hessen
Germany	Almirall Investigational Site #32	Land Niedersachsen
Germany	Almirall Investigational Site #1	Luebeck
Germany	Almirall Investigational Site #6	Mainz
Germany	Almirall Investigational Site #20	Marburg
Germany	Almirall Investigational Site #34	Muenchen
Germany	Almirall Investigational Site #18	Nuernberg
Germany	Almirall Investigational Site #22	Reinfeld
Germany	Almirall Investigational Site #25	Sachsen
Germany	Almirall Investigational Site #27	Sachsen
Germany	Almirall Investigational Site #28	Sachsen
Germany	Almirall Investigational Site #35	Sachsen
Germany	Almirall Investigational Site #8	Schwerin
Germany	Almirall Investigational Site #4	Witten
Hungary	Almirall Investigational Site #4	Balassagyarmat
Hungary	Almirall Investigational Site #12	Budapest
Hungary	Almirall Investigational Site #14	Budapest
Hungary	Almirall Investigational Site #16	Budapest
Hungary	Almirall Investigational Site #17	Budapest
Hungary	Almirall Investigational Site #5	Budapest
Hungary	Almirall Investigational Site #6	Budapest
Hungary	Almirall Investigational Site #1	Deszk
Hungary	Almirall Investigational Site #9	Komarom
Hungary	Almirall Investigational Site #2	Miskolc
Hungary	Almirall Investigational Site #15	Mosonmagyarovar
Hungary	Almirall Investigational Site #13	Nagykanizsa
Hungary	Almirall Investigational Site #3	Nyiregyhaza
Hungary	Almirall Investigational Site #7	Torokbalint
Hungary	Almirall Investigational Site #11	Zalaegerszeg
Italy	Almirall Investigational Site #15	Genova
Italy	Almirall Investigational Site #3	Parma
Italy	Almirall Investigational Site #5	Pisa
Italy	Almirall Investigational Site #1	Siena
Korea, Republic of	Almirall Investigational Site #7	Buchon-si
Korea, Republic of	Almirall Investigational Site #4	Gyeonggi-do
Korea, Republic of	Almirall Investigational Site #1	Seoul
Korea, Republic of	Almirall Investigational Site #2	Seoul
Korea, Republic of	Almirall Investigational Site #3	Seoul
Korea, Republic of	Almirall Investigational Site #5	Seoul
Korea, Republic of	Almirall Investigational Site #6	Seoul
Korea, Republic of	Almirall Investigational Site #8	Seoul
Netherlands	Almirall Investigational Site #8	Beek
Netherlands	Almirall Investigational Site #7	Breda
Netherlands	Almirall Investigational Site #13	Eindhoven
Netherlands	Almirall Investigational Site #1	Leiderdorp
Netherlands	Almirall Investigational Site #9	Rotterdam
Netherlands	Almirall Investigational Site #11	Velp
Netherlands	Almirall Investigational Site #10	Zoetermeer
Poland	Almirall Investigational Site #26	Bialystok
Poland	Almirall Investigational Site #3	Bialystok
Poland	Almirall Investigational Site #19	Bielsko-Biala
Poland	Almirall Investigational Site #23	Bydgoszcz
Poland	Almirall Investigational Site #21	Gdynia
Poland	Almirall Investigational Site #22	Katowice
Poland	Almirall Investigational Site #5	Katowice
Poland	Almirall Investigational Site #7	Krakow
Poland	Almirall Investigational Site #9	Krakow
Poland	Almirall Investigational Site #1	Lodz
Poland	Almirall Investigational Site #6	Lodz
Poland	Almirall Investigational Site #14	Lublin
Poland	Almirall Investigational Site #8	Olawa
Poland	Almirall Investigational Site #11	Poznan
Poland	Almirall Investigational Site #2	Poznan
Poland	Almirall Investigational Site #4	Poznan
Poland	Almirall Investigational Site #13	Torun
Poland	Almirall Investigational Site #18	Torun
Poland	Almirall Investigational Site #10	Warszawa
Poland	Almirall Investigational Site #15	Warszawa
Poland	Almirall Investigational Site #16	Warszawa
Romania	Almirall Investigational Site #1	Brasov
Romania	Almirall Investigational Site #10	Bucuresti
Romania	Almirall Investigational Site #18	Bucuresti
Romania	Almirall Investigational Site #7	Bucuresti
Romania	Almirall Investigational Site #9	Bucuresti
Romania	Almirall Investigational Site #17	Constanta
Romania	Almirall Investigational Site #2	Constanta
Romania	Almirall Investigational Site #3	Craiova
Romania	Almirall Investigational Site #8	Deva
Romania	Almirall Investigational Site #16	Iasi
Romania	Almirall Investigational Site #6	Iasi
Romania	Almirall Investigational Site #5	Targu Mures
Russian Federation	Almirall Investigational Site #1	Moscow
Russian Federation	Almirall Investigational Site #2	Moscow
Russian Federation	Almirall Investigational Site #9	Novosibirsk
Russian Federation	Almirall Investigational Site #12	St. Petersburg
Russian Federation	Almirall Investigational Site #7	St. Petersburg
Slovakia	Almirall Investigational Site #6	Banska Bystrica
Slovakia	Almirall Investigational Site #5	Bardejov
Slovakia	Almirall Investigational Site #3	Bratislava
Slovakia	Almirall Investigational Site #1	Nove Zamky
Slovakia	Almirall Investigational Site #4	Spisska Nova Ves
Slovakia	Almirall Investigational Site #9	Sturovo
Slovakia	Almirall Investigational Site #10	Vysne Hagy
South Africa	Almirall Investigational Site #1	Amanzimtoti
South Africa	Almirall Investigational Site #16	Cape Town
South Africa	Almirall Investigational Site #2	Cape Town
South Africa	Almirall Investigational Site #15	Cape Town, Western Cape
South Africa	Almirall Investigational Site #12	Pretoria
South Africa	Almirall Investigational Site #13	Pretoria
South Africa	Almirall Investigational Site #3	Pretoria
South Africa	Almirall Investigational Site #8	Roodepoort
South Africa	Almirall Investigational Site #5	Somerset West
Spain	Almirall Investigational Site #12	Barcelona
Spain	Almirall Investigational Site #7	Barcelona
Spain	Almirall Investigational Site #10	Caceres
Spain	Almirall Investigational Site #3	Canet de Mar
Spain	Almirall Investigational Site #1	Malaga
Spain	Almirall Investigational Site #9	Oviedo
Spain	Almirall Investigational Site #8	Sevilla
Sweden	Almirall Investigational Site #2	Göteborg
Sweden	Almirall Investigational Site #1	Lund
Sweden	Almirall Investigational Site #6	Lund
Sweden	Almirall Investigational Site #3	Malmö
Sweden	Almirall Investigational Site #4	Vällingby
Ukraine	Almirall Investigational Site #18	Crimea Oblast
Ukraine	Almirall Investigational Site #12	Dnipropetrovsk
Ukraine	Almirall Investigational Site #9	Donetsk
Ukraine	Almirall Investigational Site #11	Ivano-Frankivsk
Ukraine	Almirall Investigational Site #17	Kharkiv
Ukraine	Almirall Investigational Site #1	Kharkov
Ukraine	Almirall Investigational Site #15	Kyiv
Ukraine	Almirall Investigational Site #2	Kyiv
Ukraine	Almirall Investigational Site #3	Kyiv
Ukraine	Almirall Investigational Site #4	Kyiv
Ukraine	Almirall Investigational Site #5	Kyiv
Ukraine	Almirall Investigational Site #6	Lugansk
Ukraine	Almirall Investigational Site #8	Mykolaiv
Ukraine	Almirall Investigational Site #10	Vinnytsya
United Kingdom	Almirall Investigational Site #6	Birmingham
United Kingdom	Almirall Investigational Site #12	Bradford
United Kingdom	Almirall Investigational Site #10	Cambridge
United Kingdom	Almirall Investigational Site #13	Cardiff
United Kingdom	Almirall Investigational Site #5	Chorley
United Kingdom	Almirall Investigational Site #2	Glasgow
United Kingdom	Almirall Investigational Site #11	Hull
United Kingdom	Almirall Investigational Site #14	Liverpool
United Kingdom	Almirall Investigational Site #1	London
United Kingdom	Almirall Investigational Site #4	Manchester
United Kingdom	Almirall Investigational Site #8	Manchester
United Kingdom	Almirall Investigational Site #18	Newcastle upon Tyne
United Kingdom	Almirall Investigational Site #7	Reading
United Kingdom	Almirall Investigational Site #16	Stockton on Tees
United Kingdom	Almirall Investigational Site #15	West midlands
United Kingdom	Almirall Investigational Site #17	Wirral

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

Austria,  Belgium,  Bulgaria,  Croatia,  Czech Republic,  Denmark,  Finland,  France,  Germany,  Hungary,  Italy,  Korea, Republic of,  Netherlands,  Poland,  Romania,  Russian Federation,  Slovakia,  South Africa,  Spain,  Sweden,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline in morning pre-dose (through) Forced Expiratory Volume in one second (FEV1)	Forced Expiratory Volume in one second (FEV1)will be measured	Change from Baseline (Week 0) to 24 Weeks	No
Primary	Change from baseline in 1-hour post-morning dose Forced Expiratory Volume in one second (FEV1)	Forced Expiratory Volume in one second (FEV1)will be measured	Change from Baseline (Week 0) to 24 Weeks	No
Secondary	Improvement of Transition Dyspnoea Index (TDI) focal score	Transition Dyspnoea Index will be recorded	Change from Baseline (Week 0) to 24 Weeks	No
Secondary	Change from baseline in St. George´s Respiratory Questionnaire(SGRQ) total score	St. George´s Respiratory Questionnaire will be used to record the total score	Change from Baseline (Week 0) to 24 Weeks	No

External Links

•   CSRsynopsis