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

NCT01462942 | Completed Phase 3 Results

• 1 other identifier: M/40464/30
• Study Type: interventional
• Target: 2,443
• Locations: 22 countries
• Sites: 197

Brief 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).

Conditions

Chronic Obstructive Pulmonary Disease (COPD)

Keywords

COPD; Bronchitis; Chronic; Emphysema

Outcome Measures

Primary Outcomes (2)

• Change From Baseline in 1-hour Morning Post-dose Forced Expiratory Volume in One Second (FEV1)

  Baseline and Week 24

• Change From Baseline in Morning Pre-dose (Trough) Forced Expiratory Volume in One Second (FEV1)

  Baseline and Week 24

Secondary Outcomes (2)

• Change in Transition Dyspnoea Index (TDI) Focal Score

  Baseline and Week 24

• Change From Baseline in St. George´s Respiratory Questionnaire (SGRQ) Total Score

  Baseline and Week 24

Study Arms (5)

Aclidinium/Formoterol 400/6 μg

EXPERIMENTAL

24 week, double blind treatment period

Drug: Aclidinium Bromide/Formoterol Fumarate

Aclidinium/Formoterol 400/12 μg

EXPERIMENTAL

24 week, double blind treatment period

Drug: Aclidinium Bromide/Formoterol Fumarate

Aclidinium monotherapy 400 μg

EXPERIMENTAL

24 week, double blind treatment period

Drug: Aclidinium Bromide

Formoterol monotherapy 12 μg

ACTIVE COMPARATOR

24 week, double blind treatment period

Drug: Formoterol Fumarate

Placebo

PLACEBO COMPARATOR

24 week, double blind treatment period

Drug: Placebo

Interventions

Aclidinium Bromide/Formoterol Fumarate DRUG

Inhaled Aclidinium/formoterol Fixed Dose Combination (FDC) low dose (400/6 μg), twice per day

Aclidinium/Formoterol 400/6 μg

Aclidinium Bromide DRUG

Inhaled Aclidinium 400 μg, twice per day

Aclidinium monotherapy 400 μg

Placebo DRUG

Inhaled dose-matched placebo, twice per day

Placebo

Formoterol Fumarate DRUG

Inhaled Formoterol 12 μg, twice per day

Formoterol monotherapy 12 μg

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.
• Patients who in the Investigator's opinion might have needed to start a pulmonary rehabilitation program during the study and/or patients who started/finished it within 3 months prior to screening.
• Use of long-term oxygen therapy (≥ 15 hours/day).
• Patients who did not maintain regular day/night, waking/sleeping cycles including night shift workers (eg, history of sleep apnoea syndrome, any condition related to sleep disturbances such as restless-legs syndrome or somnambulism).
• Clinically significant cardiovascular conditions defined as:
• Myocardial infarction within the 6 months prior to screening.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (197)

Almirall Investigational Site #2

Graz, 8036, Austria

Location

Almirall Investigational Site #3

Salzburg, 5020, Austria

Location

Almirall Investigational Site #3

Edegem, 2650, Belgium

Location

Almirall Investigational Site #2

Genk, 3600, Belgium

Location

Almirall Investigational Site #6

Rousse, 7002, Bulgaria

Location

Almirall Investigational Site #10

Sevlievo, 5400, Bulgaria

Location

Almirall Investigational Site #8

Sofia, 1000, Bulgaria

Location

Almirall Investigational Site #2

Sofia, 1431, Bulgaria

Location

Almirall Investigational Site #11

Sofia, 1709, Bulgaria

Location

Almirall Investigational Site #2

Zagreb, 10000, Croatia

Location

Almirall Investigational Site #4

Zagreb, 10000, Croatia

Location

Almirall Investigational Site #8

Brno, 65691, Czechia

Location

Almirall Investigational Site #3

Jindřichův Hradec, 377 01, Czechia

Location

Almirall Investigational Site #10

Karlovy Vary, 360 00, Czechia

Location

Almirall Investigational Site #9

Liberec, 460 63, Czechia

Location

Almirall Investigational Site #16

Ostrava Hrabuvka, 700 30, Czechia

Location

Almirall Investigational Site #2

Prague, 130 00, Czechia

Location

Almirall Investigational Site #12

Prague, 155 00, Czechia

Location

Almirall Investigational Site #15

Prague, 163 00, Czechia

Location

Almirall Investigational Site #14

Prague, 18200, Czechia

Location

Almirall Investigational Site #6

Praha 5 - Radotin, 153 00, Czechia

Location

Almirall Investigational Site #11

Strakonice, 386 01, Czechia

Location

Almirall Investigational Site #1

Tábor, 390 01, Czechia

Location

Almirall Investigational Site #4

Hillerød, 3400, Denmark

Location

Almirall Investigational Site #1

København NV, 2400, Denmark

Location

Almirall Investigational Site #5

Odense, 5000, Denmark

Location

Almirall Investigational Site #2

Silkeborg, 8600, Denmark

Location

Almirall Investigational Site #7

Espoo, 2740, Finland

Location

Almirall Investigational Site #8

Jyväskylä, 40100, Finland

Location

Almirall Investigational Site #1

Tampere, 33520, Finland

Location

Almirall Investigational Site #6

Tampere, 33520, Finland

Location

Almirall Investigational Site #3

Turku, 20520, Finland

Location

Almirall Investigational Site #6

Lille, 59037, France

Location

Almirall Investigational Site #10

Marseille, 13291, France

Location

Almirall Investigational Site #11

Montpellier, 34295, France

Location

Almirall Investigational Site #1

Pessac, 33604, France

Location

Almirall Investigational Site #3

Rennes, 35033, France

Location

Almirall Investigational Site #8

Toulouse, 31059, France

Location

Almirall Investigational Site #12

Vieux-Condé, 59690, France

Location

Almirall Investigational Site #2

Berlin, 10117, Germany

Location

Almirall Investigational Site #12

Berlin, 10629, Germany

Location

Almirall Investigational Site #19

Berlin, 12627, Germany

Location

Almirall Investigational Site #11

Berlin, 13125, Germany

Location

Almirall Investigational Site #24

Berlin, 14059, Germany

Location

Almirall Investigational Site #16

Bochum, 44787, Germany

Location

Almirall Investigational Site #23

Bonn, 53123, Germany

Location

Almirall Investigational Site #15

Dresden, 1067, Germany

Location

Almirall Investigational Site #10

Dresden, 1307, Germany

Location

Almirall Investigational Site #5

Frankfurt, 60389, Germany

Location

Almirall Investigational Site #13

Frankfurt, 60596, Germany

Location

Almirall Investigational Site #33

Haltern am See, 44263, Germany

Location

Almirall Investigational Site #7

Hamburg, 20253, Germany

Location

Almirall Investigational Site #21

Hamburg, 22143, Germany

Location

Almirall Investigational Site #36

Hessen, 60596, Germany

Location

Almirall Investigational Site #32

Land Niedersachsen, 30159, Germany

Location

Almirall Investigational Site #1

Lübeck, 23538, Germany

Location

Almirall Investigational Site #6

Mainz, 55131, Germany

Location

Almirall Investigational Site #20

Marburg, 35037, Germany

Location

Almirall Investigational Site #34

München, 80539, Germany

Location

Almirall Investigational Site #18

Nuremberg, 90402, Germany

Location

Almirall Investigational Site #22

Reinfeld, 23858, Germany

Location

Almirall Investigational Site #35

Sachsen, 1067, Germany

Location

Almirall Investigational Site #27

Sachsen, 2826, Germany

Location

Almirall Investigational Site #28

Sachsen, 39104, Germany

Location

Almirall Investigational Site #25

Sachsen, 4103, Germany

Location

Almirall Investigational Site #8

Schwerin, 19055, Germany

Location

Almirall Investigational Site #4

Witten, 58452, Germany

Location

Almirall Investigational Site #4

Balassagyarmat, 2660, Hungary

Location

Almirall Investigational Site #16

Budapest, 1033, Hungary

Location

Almirall Investigational Site #12

Budapest, 1036, Hungary

Location

Almirall Investigational Site #17

Budapest, 1036, Hungary

Location

Almirall Investigational Site #6

Budapest, 1125, Hungary

Location

Almirall Investigational Site #14

Budapest, 1221, Hungary

Location

Almirall Investigational Site #5

Budapest, 1529, Hungary

Location

Almirall Investigational Site #1

Deszk, 6772, Hungary

Location

Almirall Investigational Site #9

Komárom, 2900, Hungary

Location

Almirall Investigational Site #2

Miskolc, 3534, Hungary

Location

Almirall Investigational Site #15

Mosonmagyaróvár, 9200, Hungary

Location

Almirall Investigational Site #13

Nagykanizsa, 8800, Hungary

Location

Almirall Investigational Site #3

Nyíregyháza, 4400, Hungary

Location

Almirall Investigational Site #7

Törökbálint, 2045, Hungary

Location

Almirall Investigational Site #11

Zalaegerszeg, 8900, Hungary

Location

Almirall Investigational Site #15

Genova, 16132, Italy

Location

Almirall Investigational Site #3

Parma, 43100, Italy

Location

Almirall Investigational Site #5

Pisa, 56124, Italy

Location

Almirall Investigational Site #1

Siena, 53100, Italy

Location

Almirall Investigational Site #8

Beek, 6191 JW, Netherlands

Location

Almirall Investigational Site #7

Breda, 4811 VL, Netherlands

Location

Almirall Investigational Site #13

Eindhoven, 5632 EJ, Netherlands

Location

Almirall Investigational Site #1

Leiderdorp, 2352 RA, Netherlands

Location

Almirall Investigational Site #9

Rotterdam, 3021 HC, Netherlands

Location

Almirall Investigational Site #11

Velp, 6883 ES, Netherlands

Location

Almirall Investigational Site #10

Zoetermeer, 2724 EK, Netherlands

Location

Almirall Investigational Site #26

Bialystok, 15-003, Poland

Location

Almirall Investigational Site #3

Bialystok, 15-540, Poland

Location

Almirall Investigational Site #19

Bielsko-Biala, 43-316, Poland

Location

Almirall Investigational Site #23

Bydgoszcz, 85-079, Poland

Location

Almirall Investigational Site #21

Gdynia, 81-384, Poland

Location

Almirall Investigational Site #5

Katowice, 40-748, Poland

Location

Almirall Investigational Site #22

Katowice, 40-751, Poland

Location

Almirall Investigational Site #7

Krakow, 31-024, Poland

Location

Almirall Investigational Site #9

Krakow, 31-159, Poland

Location

Almirall Investigational Site #6

Lodz, 92-216, Poland

Location

Almirall Investigational Site #1

Lodz, 93-319, Poland

Location

Almirall Investigational Site #14

Lublin, 20-718, Poland

Location

Almirall Investigational Site #8

Oława, 55-200, Poland

Location

Almirall Investigational Site #2

Poznan, 60-214, Poland

Location

Almirall Investigational Site #11

Poznan, 60-693, Poland

Location

Almirall Investigational Site #4

Poznan, 60-823, Poland

Location

Almirall Investigational Site #13

Torun, 87-100, Poland

Location

Almirall Investigational Site #18

Torun, 87-100, Poland

Location

Almirall Investigational Site #10

Warsaw, 01-138, Poland

Location

Almirall Investigational Site #15

Warsaw, 01-138, Poland

Location

Almirall Investigational Site #16

Warsaw, 01-868, Poland

Location

Almirall Investigational Site #1

Brasov, 500075, Romania

Location

Almirall Investigational Site #9

Bucharest, 21382, Romania

Location

Almirall Investigational Site #18

Bucharest, 21659, Romania

Location

Almirall Investigational Site #7

Bucharest, 30303, Romania

Location

Almirall Investigational Site #10

Bucharest, 50554, Romania

Location

Almirall Investigational Site #17

Constanța, 900002, Romania

Location

Almirall Investigational Site #2

Constanța, 900002, Romania

Location

Almirall Investigational Site #3

Craiova, 200515, Romania

Location

Almirall Investigational Site #8

Deva, 330084, Romania

Location

Almirall Investigational Site #6

Iași, 700115, Romania

Location

Almirall Investigational Site #16

Iași, 700381, Romania

Location

Almirall Investigational Site #5

Târgu Mureş, RO540136, Romania

Location

Almirall Investigational Site #2

Moscow, 109240, Russia

Location

Almirall Investigational Site #1

Moscow, 119620, Russia

Location

Almirall Investigational Site #9

Novosibirsk, 630089, Russia

Location

Almirall Investigational Site #7

Saint Petersburg, 194044, Russia

Location

Almirall Investigational Site #12

Saint Petersburg, 194354, Russia

Location

Almirall Investigational Site #6

Banská Bystrica, 975 17, Slovakia

Location

Almirall Investigational Site #5

Bardejov, 8501, Slovakia

Location

Almirall Investigational Site #3

Bratislava, 821 06, Slovakia

Location

Almirall Investigational Site #1

Nové Zámky, 940 01, Slovakia

Location

Almirall Investigational Site #4

Spišská Nová Ves, 5201, Slovakia

Location

Almirall Investigational Site #9

Štúrovo, 943 01, Slovakia

Location

Almirall Investigational Site #10

Vyšné Hágy, 059 84, Slovakia

Location

Almirall Investigational Site #16

Cape Town, 7500, South Africa

Location

Almirall Investigational Site #2

Cape Town, 7500, South Africa

Location

Almirall Investigational Site #15

Cape Town, Western Cape, 7700, South Africa

Location

Almirall Investigational Site #1

eManzimtoti, 4126, South Africa

Location

Almirall Investigational Site #12

Pretoria, 2, South Africa

Location

Almirall Investigational Site #13

Pretoria, 2, South Africa

Location

Almirall Investigational Site #3

Pretoria, 84, South Africa

Location

Almirall Investigational Site #8

Roodepoort, 1724, South Africa

Location

Almirall Investigational Site #5

Somerset West, 7129, South Africa

Location

Almirall Investigational Site #7

Buchon-si, 420-767, South Korea

Location

Almirall Investigational Site #4

Gyeonggi-do, 431-070, South Korea

Location

Almirall Investigational Site #8

Seoul, 110-744, South Korea

Location

Almirall Investigational Site #6

Seoul, 120-752, South Korea

Location

Almirall Investigational Site #3

Seoul, 136-705, South Korea

Location

Almirall Investigational Site #5

Seoul, 137-710, South Korea

Location

Almirall Investigational Site #2

Seoul, 152-703, South Korea

Location

Almirall Investigational Site #1

Seoul, 158-710, South Korea

Location

Almirall Investigational Site #7

Barcelona, 8003, Spain

Location

Almirall Investigational Site #12

Barcelona, 8916, Spain

Location

Almirall Investigational Site #3

Canet de Mar, 8360, Spain

Location

Almirall Investigational Site #10

Cáceres, 10003, Spain

Location

Almirall Investigational Site #1

Málaga, 29010, Spain

Location

Almirall Investigational Site #9

Oviedo, 33006, Spain

Location

Almirall Investigational Site #8

Seville, 41071, Spain

Location

Almirall Investigational Site #2

Gothenburg, 41263, Sweden

Location

Almirall Investigational Site #1

Lund, 22185, Sweden

Location

Almirall Investigational Site #6

Lund, 22222, Sweden

Location

Almirall Investigational Site #3

Malmo, 21152, Sweden

Location

Almirall Investigational Site #4

Vällingby, 16268, Sweden

Location

Almirall Investigational Site #18

Crimea Oblast, 98603, Ukraine

Location

Almirall Investigational Site #12

Dnipropetrovsk, 49051, Ukraine

Location

Almirall Investigational Site #9

Donetsk, 83099, Ukraine

Location

Almirall Investigational Site #11

Ivano-Frankivsk, 76012, Ukraine

Location

Almirall Investigational Site #1

Kharkiv, 61035, Ukraine

Location

Almirall Investigational Site #17

Kharkiv, 61039, Ukraine

Location

Almirall Investigational Site #15

Kyiv, 03680, Ukraine

Location

Almirall Investigational Site #2

Kyiv, 3680, Ukraine

Location

Almirall Investigational Site #3

Kyiv, 3680, Ukraine

Location

Almirall Investigational Site #4

Kyiv, 3680, Ukraine

Location

Almirall Investigational Site #5

Kyiv, 4050, Ukraine

Location

Almirall Investigational Site #6

Luhansk, 91045, Ukraine

Location

Almirall Investigational Site #8

Mykolaiv, 54003, Ukraine

Location

Almirall Investigational Site #10

Vinnytsia, 21029, Ukraine

Location

Almirall Investigational Site #6

Birmingham, B15 2SQ, United Kingdom

Location

Almirall Investigational Site #12

Bradford, BD9 6RJ, United Kingdom

Location

Almirall Investigational Site #10

Cambridge, CB2 2QQ, United Kingdom

Location

Almirall Investigational Site #13

Cardiff, CF14 5GJ, United Kingdom

Location

Almirall Investigational Site #5

Chorley, PR7 7NA, United Kingdom

Location

Almirall Investigational Site #2

Glasgow, G81 2DR, United Kingdom

Location

Almirall Investigational Site #11

Hull, HU16 5JQ, United Kingdom

Location

Almirall Investigational Site #14

Liverpool, L22 0LG, United Kingdom

Location

Almirall Investigational Site #1

London, E2 9JX, United Kingdom

Location

Almirall Investigational Site #4

Manchester, M15 6SX, United Kingdom

Location

Almirall Investigational Site #8

Manchester, M23 9QZ, United Kingdom

Location

Almirall Investigational Site #17

Metropolitan Borough of Wirral, CH49 5PE, United Kingdom

Location

Almirall Investigational Site #18

Newcastle upon Tyne, NE7 7DN, United Kingdom

Location

Almirall Investigational Site #7

Reading, RG2 7AG, United Kingdom

Location

Almirall Investigational Site #16

Stockton-on-Tees, TS19 8PE, United Kingdom

Location

Almirall Investigational Site #15

West Midlands, WV10 0QP, United Kingdom

Location

Related Publications (4)

• Singh D, D'Urzo AD, Donohue JF, Kerwin EM, Molins E, Chuecos F, Ribera A, Jarreta D. An Evaluation Of Single And Dual Long-Acting Bronchodilator Therapy As Effective Interventions In Maintenance Therapy-Naive Patients With COPD. Int J Chron Obstruct Pulmon Dis. 2019 Dec 6;14:2835-2848. doi: 10.2147/COPD.S217710. eCollection 2019.

  PMID: 31827323 DERIVED

• Singh D, D'Urzo AD, Chuecos F, Munoz A, Garcia Gil E. Reduction in clinically important deterioration in chronic obstructive pulmonary disease with aclidinium/formoterol. Respir Res. 2017 May 30;18(1):106. doi: 10.1186/s12931-017-0583-0.

  PMID: 28558833 DERIVED

• Bateman ED, Chapman KR, Singh D, D'Urzo AD, Molins E, Leselbaum A, Gil EG. Aclidinium bromide and formoterol fumarate as a fixed-dose combination in COPD: pooled analysis of symptoms and exacerbations from two six-month, multicentre, randomised studies (ACLIFORM and AUGMENT). Respir Res. 2015 Aug 2;16(1):92. doi: 10.1186/s12931-015-0250-2.

  PMID: 26233481 DERIVED

• Singh D, Jones PW, Bateman ED, Korn S, Serra C, Molins E, Caracta C, Gil EG, Leselbaum A. Efficacy and safety of aclidinium bromide/formoterol fumarate fixed-dose combinations compared with individual components and placebo in patients with COPD (ACLIFORM-COPD): a multicentre, randomised study. BMC Pulm Med. 2014 Nov 18;14:178. doi: 10.1186/1471-2466-14-178.

  PMID: 25404569 DERIVED

Related Links

• CSRsynopsis

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive; Bronchitis; Bronchiolitis Obliterans Syndrome; Emphysema

Interventions

aclidinium bromide; Formoterol Fumarate

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Respiratory Tract Infections; Infections; Bronchial Diseases; Organizing Pneumonia; Bronchiolitis Obliterans; Bronchiolitis; Graft vs Host Disease; Immune System Diseases

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines

Results Point of Contact

• Title: Esther Garcia
• Organization: AstraZeneca

ClinicalTrialTransparency@astrazeneca.com

Study Officials

• Esther Garcia, Ph.D.

  AstraZeneca

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 26, 2011
• First Posted: November 1, 2011
• Study Start: October 1, 2011
• Primary Completion: January 1, 2013
• Study Completion: January 1, 2013
• Last Updated: February 15, 2017
• Results First Posted: February 15, 2017

Record last verified: 2016-12

Locations

RO (12); DE (28); BU (5); GB (16); ZA (9); HU (15); CR (2); CZ (12); AU (2); DK (4); FI (5); PL (21); RU (5); SL (7); KR (8); SE (5); UA (14); FR (7); ES (7); BE (2); IT (4); NL (7)