Efficacy, Safety and Tolerability of Aclidinium Bromide/Formoterol Fumarate Compared With Aclidinium Bromide and Formoterol Fumarate in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD)

A Phase III, Randomized, Double-blind, Placebo-Controlled Study Evaluating the Efficacy, Safety, and Tolerability of Two Fixed Dose Combinations of Aclidinium Bromide/Formoterol Fumarate Compared With Aclidinium Bromide, Formoterol Fumarate and Placebo for 24- Weeks Treatment in Patients With Moderate to Severe, Stable Chronic Obstructive Pulmonary Disease (COPD).

The purpose of this Phase III study is to assess the maintenance bronchodilator effects of the fixed dose combination versus monotherapies. This study will also assess the effects of the fixed dose combination in terms of COPD symptoms, disease related health status and the long-term safety and tolerability of the fixed dose combination. This study will include a 24 week treatment period, preceding by a run-in period, followed by a two week follow up visit. All patients will be randomized to one of four treatment arms or placebo.

Study Overview

• Status: Completed
• Conditions: Chronic Obstructive Pulmonary Disease
• Intervention / Treatment: Drug: Aclidinium Bromide/Formoterol Fumarate; Drug: Aclidinium Bromide/Formoterol Fumarate; Drug: Aclidinium Bromide; Drug: Formoterol Fumarate; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 1692
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • New Lambton, New South Wales, Australia, 2305
      • Forest Investigative Site 1991
  • Queensland
    • Redcliffe, Queensland, Australia, 4020
      • Forest Investigative Site 1987
    • Woolloongabba, Queensland, Australia, 4102
      • Forest Investigative Site 1973
  • South Australia
    • Bedford Park, South Australia, Australia, 5042
      • Forest Investigative Site 1981
    • Daw Park, South Australia, Australia, 5041
      • Forest Investigative Site 1990
    • Toorak Gardens, South Australia, Australia, 5065
      • Forest Investigative Site 2251
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Forest Investigative Site 2250
    • Fitzroy, Victoria, Australia, 3011
      • Forest Investigative Site 1972
    • Geelong, Victoria, Australia, 3220
      • Forest Investigative Site 1986
    • Parkville, Victoria, Australia, 3050
      • Forest Investigative Site 1985
  • Western Australia
    • Adelaide, Western Australia, Australia, 5000
      • Forest Investigative Site 2253
• Canada
  • Quebec, Canada, G1V 4M6
    • Forest Investigative Site 1859
  • British Columbia
    • Langley, British Columbia, Canada, V3A 4H9
      • Forest Investigative Site 1904
    • Vancouver, British Columbia, Canada, V5Z 1M9
      • Forest Investigative Site 0905
  • Manitoba
    • Winnipeg, Manitoba, Canada, R2K 3S8
      • Forest Investigative Site 0976
  • Ontario
    • Sarina, Ontario, Canada, N7T 4X3
      • Forest Investigative Site 1877
    • Sarnia, Ontario, Canada, N7T 4X3
      • Forest Investigative Site 1896
    • Toronto, Ontario, Canada, M5T 3A9
      • Forest Investigative Site 1171
    • Toronto, Ontario, Canada, M6H 3M2
      • Forest Investigative Site 2203
  • Quebec
    • Montreal, Quebec, Canada, H2R 1V6
      • Forest Investigative Site 1952
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada, S7N0W8
      • Forest Investigative Site 0943
• New Zealand
  • Auckland, New Zealand, 1051
    • Forest Investigative Site 1027
  • Christchurch, New Zealand, 8011
    • Forest Investigative Site 1970
  • Dunedin, New Zealand, 9012
    • Forest Investigative Site 1967
  • Dunedin, New Zealand, 9058
    • Forest Investigative Site 1964
  • Hamilton, New Zealand, 3240
    • Forest Investigative Site 1968
  • Tauranga, New Zealand, 3110
    • Forest Investigative Site 1965
  • Tauranga, New Zealand, 3112
    • Forest Investigative Site 1980
  • Wellington, New Zealand, 7366
    • Forest Investigative Site 1025
• United States
  • Alabama
    • Anniston, Alabama, United States, 36207
      • Forest Investigative Site 1827
    • Athens, Alabama, United States, 35611
      • Forest Investigative Site 1920
    • Birmingham, Alabama, United States, 35209
      • Forest Investigative Site 1162
    • Birmingham, Alabama, United States, 35209
      • Forest Investigative Site 1493
    • Birmingham, Alabama, United States, 35216
      • Forest Investigative Site 1937
    • Florence, Alabama, United States, 35630
      • Forest Investigative Site 1893
    • Gulf Shores, Alabama, United States, 36542
      • Forest Investigative Site 1824
    • Jasper, Alabama, United States, 35501
      • Forest Investigative Site 2088
    • Scottsboro, Alabama, United States, 35768
      • Forest Investigative Site 1918
  • Arizona
    • Glendale, Arizona, United States, 85306
      • Forest Investigative Site 0909
    • Mesa, Arizona, United States, 85206
      • Forest Investigative Site 1958
    • Phoenix, Arizona, United States, 85018
      • Forest Investigative Site 1379
  • California
    • Anaheim, California, United States, 92801
      • Forest Investigative Site 1822
    • Buena Park, California, United States, 90620
      • Forest Investigative Site 1483
    • Fountain Valley, California, United States, 92708
      • Forest Investigative Site 1809
    • Fresno, California, United States, 93726
      • Forest Investigative Site 1156
    • Lincoln, California, United States, 95648
      • Forest Investigative Site 1871
    • Los Angeles, California, United States, 90073
      • Forest Investigative Site 1873
    • Riverside, California, United States, 92506
      • Forest Investigative Site 2064
    • Sacramento, California, United States, 95817
      • Forest Investigative Site 1427
    • Sacramento, California, United States, 95842
      • Forest Investigative Site 1866
    • San Diego, California, United States, 92103
      • Forest Investigative Site 1125
    • San Diego, California, United States, 92111
      • Forest Investigative Site 1898
    • San Diego, California, United States, 92120
      • Forest Investigative Site 2009
    • Torrance, California, United States, 90505
      • Forest Investigative Site 1374
    • Tustin, California, United States, 92780
      • Forest Investigative Site 1813
    • Vista, California, United States, 92083
      • Forest Investigative Site 1883
  • Colorado
    • Golden, Colorado, United States, 80401
      • Forest Investigative Site 1380
    • Pueblo, Colorado, United States, 81001
      • Forest Investigative Site 1137
    • Wheat Ridge, Colorado, United States, 80033
      • Forest Investigative Site 1327
  • Connecticut
    • Waterbury, Connecticut, United States, 06708
      • Forest Investigative Site 1976
  • Florida
    • Bay Pines, Florida, United States, 33744
      • Forest Investigative Site 1821
    • Brandon, Florida, United States, 33511
      • Forest Investigative Site 1154
    • Brandon, Florida, United States, 33511
      • Forest Investigative Site 1944
    • Clearwater, Florida, United States, 33756
      • Forest Investigative Site 1364
    • Clearwater, Florida, United States, 33765
      • Forest Investigative Site 1152
    • Clearwater, Florida, United States, 33765
      • Forest Investigative Site 1875
    • DeLand, Florida, United States, 32720
      • Forest Investigative Site 0670
    • Edgewater, Florida, United States, 32132
      • Forest Investigative Site 1516
    • Fort Lauderdale, Florida, United States, 33316
      • Forest Investigative Site 0990
    • Hialeah, Florida, United States, 33012
      • Forest Investigative Site 1513
    • Hialeah, Florida, United States, 33012
      • Forest Investigative Site 1854
    • Hollywood, Florida, United States, 33024
      • Forest Investigative Site 1882
    • Jacksonville, Florida, United States, 32216
      • Forest Investigative Site 1543
    • Kissimmee, Florida, United States, 34741
      • Forest Investigative Site 1416
    • Melbourne, Florida, United States, 32935
      • Forest Investigative Site 1167
    • Miami, Florida, United States, 33135
      • Forest Investigative Site 1868
    • Miami, Florida, United States, 33143
      • Forest Investigative Site 1432
    • Miami, Florida, United States, 33144
      • Forest Investigative Site 1979
    • Naples, Florida, United States, 34119
      • Forest Investigative Site 1819
    • North Miami Beach, Florida, United States, 33179
      • Forest Investigative Site 1808
    • Oldsmar, Florida, United States, 34677
      • Forest Investigative Site 1950
    • Ormond Beach, Florida, United States, 32174
      • Forest Investigative Site 1145
    • Panama City, Florida, United States, 32405
      • Forest Investigative Site 1094
    • Pembroke Pines, Florida, United States, 33028
      • Forest Investigative Site 1803
    • Pensacola, Florida, United States, 32504
      • Forest Investigative Site 974
    • Saint Petersburg, Florida, United States, 33701
      • Forest Investigative Site 1876
    • Sarasota, Florida, United States, 34233
      • Forest Investigative Site 1817
    • St. Cloud, Florida, United States, 34769
      • Forest Investigative Site 1829
    • St. Petersburg, Florida, United States, 33704
      • Forest Investigative Site 1874
    • Tamarac, Florida, United States, 33321
      • Forest Investigative Site 2082
    • Tampa, Florida, United States, 33603
      • Forest Investigative Site 2053
    • Tampa, Florida, United States, 33613
      • Forest Investigative Site 2047
    • Winter Park, Florida, United States, 32789
      • Forest Investigative Site 1185
    • Winter Park, Florida, United States, 32792
      • Forest Investigative Site 1860
  • Georgia
    • Albany, Georgia, United States, 31707
      • Forest Investigative Site 1982
    • Atlanta, Georgia, United States, 30312
      • Forest Investigative Site 1900
    • Austell, Georgia, United States, 30106
      • Forest Investigative Site 0987
    • Canton, Georgia, United States, 30114
      • Forest Investigative Site 1828
    • Marietta, Georgia, United States, 30066
      • Forest Investigative Site 1830
    • Woodstock, Georgia, United States, 30189
      • Forest Investigative Site 2089
  • Idaho
    • Coeur d' Alene, Idaho, United States, 83814
      • Forest Investigative Site 0679
    • Eagle, Idaho, United States, 83616
      • Forest Investigative Site 1858
  • Illinois
    • Normal, Illinois, United States, 61761
      • Forest Investigative Site 1095
    • Normal, Illinois, United States, 61761
      • Forest Investigative Site 1912
    • River Forest, Illinois, United States, 60305
      • Forest Investigative Site 2051
  • Kentucky
    • Bowling Green, Kentucky, United States, 42101
      • Forest Investigative Site 2033
    • Fort Mitchell, Kentucky, United States, 41017
      • Forest Investigative Site 2085
    • Lexington, Kentucky, United States, 40504
      • Forest Investigative Site 0539
    • Louisville, Kentucky, United States, 40217
      • Forest Investigative Site 1478
    • Owensboro, Kentucky, United States, 42303
      • Forest Investigative Site 1519
  • Louisiana
    • Covington, Louisiana, United States, 70433
      • Forest Investigative Site 1811
    • New Orleans, Louisiana, United States, 70115
      • Forest Investigative Site 1430
    • Opelousas, Louisiana, United States, 70570
      • Forest Investigative Site 1812
  • Maine
    • Bangor, Maine, United States, 04401
      • Forest Investigative Site 1814
  • Maryland
    • Baltimore, Maryland, United States, 21237
      • Forest Investigative Site 1924
    • Hollywood, Maryland, United States, 20636
      • Forest Investigative Site 1865
    • Wheaton, Maryland, United States, 20902
      • Forest Investigative Site 1872
  • Massachusetts
    • Fall River, Massachusetts, United States, 02720
      • Forest Investigative Site 1570
    • Fall river, Massachusetts, United States, 02720
      • Forest Investigative Site 1852
    • North Dartmouth, Massachusetts, United States, 02747
      • Forest Investigative Site 1029
    • North Dartmouth, Massachusetts, United States, 02747
      • Forest Investigative Site 1431
  • Michigan
    • Ann Arbor, Michigan, United States, 48106
      • Forest Investigative Site 1892
    • Stevensville, Michigan, United States, 49127
      • Forest Investigative Site 1342
    • Troy, Michigan, United States, 48085
      • Forest Investigative Site 1487
  • Minnesota
    • Edina, Minnesota, United States, 55435
      • Forest Investigative Site 1128
    • Fridley, Minnesota, United States, 55432
      • Forest Investigative Site 1527
    • Minneapolis, Minnesota, United States, 55402
      • Forest Investigative Site 2041
    • Minneapolis, Minnesota, United States, 55407
      • Forest Investigative Site 1124
    • Plymouth, Minnesota, United States, 55441
      • Forest Investigative Site 1619
    • Rochester, Minnesota, United States, 55905
      • Forest Investigative Site 1118
  • Mississippi
    • Olive Branch, Mississippi, United States, 38654
      • Forest Investigative Site 1884
  • Missouri
    • Chesterfield, Missouri, United States, 63017
      • Forest Investigative Site 1587
    • Kansas City, Missouri, United States, 64128
      • Forest Investigative Site 1602
    • Springfield, Missouri, United States, 65803
      • Forest Investigative Site 1856
    • Springfield, Missouri, United States, 65807
      • Forest Investigative Site 1867
    • St. Charles, Missouri, United States, 63301
      • Forest Investigative Site 2079
    • St. Louis, Missouri, United States, 63141
      • Forest Investigative Site 1399
    • St. Louis, Missouri, United States, 63141
      • Forest Investigative Site 1599
  • Montana
    • Bozeman, Montana, United States, 59718
      • Forest Investigative Site 1831
    • Missoula, Montana, United States, 59808
      • Forest Investigative Site 1400
  • Nebraska
    • Bellevue, Nebraska, United States, 68123
      • Forest Investigative Site 1609
    • Fremont, Nebraska, United States, 68025
      • Forest Investigative Site 1948
    • Lincoln, Nebraska, United States, 68510
      • Forest Investigative Site 1815
    • Omaha, Nebraska, United States, 68114
      • Forest Investigative Site 1363
    • Omaha, Nebraska, United States, 68130
      • Forest Investigative Site 1907
    • Omaha, Nebraska, United States, 68131
      • Forest Investigative Site 1911
    • Omaha, Nebraska, United States, 68134
      • Forest Investigative Site 1908
    • Omaha, Nebraska, United States, 68144
      • Forest Investigative Site 1804
  • Nevada
    • Henderson, Nevada, United States, 89052
      • Forest Investigative Site 1807
    • Las Vegas, Nevada, United States, 89128
      • Forest Investigative Site 1834
    • Las Vegas, Nevada, United States, 89183
      • Forest Investigative Site 1562
  • New Jersey
    • Cherry Hill, New Jersey, United States, 08003
      • Forest Investigative Site 1559
    • Hackensack, New Jersey, United States, 07601
      • Forest Investigative Site 1923
  • New Mexico
    • Albuquerque, New Mexico, United States, 87106
      • Forest Investigative Site 1949
  • New York
    • Great Neck, New York, United States, 11021
      • Forest Investigative Site 1151
    • Larchmont, New York, United States, 10538
      • Forest Investigative Site 1489
    • New York, New York, United States, 10003
      • Forest Investigative Site 0550
    • New York, New York, United States, 10028
      • Forest Investigative Site 1425
    • Rochester, New York, United States, 14618
      • Forest Investigative Site 2098
  • North Carolina
    • Charlotte, North Carolina, United States, 28277
      • Forest Investigative Site 1392
    • Elizabeth City, North Carolina, United States, 27909
      • Forest Investigative Site 2035
    • High Point, North Carolina, United States, 27262
      • Forest Investigative Site 1366
    • Raleigh, North Carolina, United States, 27607
      • Forest Investigative Site 1153
    • Salisbury, North Carolina, United States, 28144
      • Forest Investigative Site 1823
  • Ohio
    • Cadiz, Ohio, United States, 43907
      • Forest Investigative Site 1891
    • Canton, Ohio, United States, 44718
      • Forest Investigative Site 1134
    • Cincinnati, Ohio, United States, 45219
      • Forest Investigative Site 1885
    • Cincinnati, Ohio, United States, 45231
      • Forest Investigative Site 1806
    • Cincinnati, Ohio, United States, 45242
      • Forest Investigative Site 2028
    • Cincinnati, Ohio, United States, 45245
      • Forest Investigative Site 1903
    • Columbus, Ohio, United States, 43207
      • Forest Investigative Site 1361
    • Columbus, Ohio, United States, 43213
      • Forest Investigative Site 1433
    • Sylvania, Ohio, United States, 43560
      • Forest Investigative Site 2090
    • Toledo, Ohio, United States, 43608
      • Forest Investigative Site 1530
    • Zanesville, Ohio, United States, 43701
      • Forest Investigative Site 1393
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73103
      • Forest Investigative Site 1915
  • Oregon
    • Bend, Oregon, United States, 97701
      • Forest Investigative Site 1889
    • Medford, Oregon, United States, 97504
      • Forest Investigative Site 2043
  • Pennsylvania
    • Altoona, Pennsylvania, United States, 16601
      • Forest Investigative Site 1833
    • Clairton, Pennsylvania, United States, 15025
      • Forest Investigative Site 1855
    • Downington, Pennsylvania, United States, 19335
      • Forest Investigative Site 1820
    • Erie, Pennsylvania, United States, 16508
      • Forest Investigative Site 1423
    • Langhorne, Pennsylvania, United States, 19047
      • Forest Investigative Site 1899
    • Philadelphia, Pennsylvania, United States, 19107
      • Forest Investigative Site 1443
    • Phoenixville, Pennsylvania, United States, 19460
      • Forest Investigative Site 1863
    • Pittsburgh, Pennsylvania, United States, 15243
      • Forest Investigative Site 1146
    • Tipton, Pennsylvania, United States, 16684
      • Forest Investigative Site 1449
    • Uniontown, Pennsylvania, United States, 15473
      • Forest Investigative Site 1862
  • Rhode Island
    • Cumberland, Rhode Island, United States, 02864
      • Forest Investigative Site 1832
    • East Providence, Rhode Island, United States, 02914
      • Forest Investigative Site 1089
  • South Carolina
    • Charleston, South Carolina, United States, 29406
      • Forest Investigative Site 2072
    • Charleston, South Carolina, United States, 29407
      • Forest Investigative Site 1905
    • Charleston, South Carolina, United States, 29412
      • Forest Investigative Site 1802
    • Fort Mill, South Carolina, United States, 29707
      • Forest Investigative Site 1914
    • Gaffney, South Carolina, United States, 29340
      • Forest Investigative Site 1913
    • Spartanburg, South Carolina, United States, 29303
      • Forest Investigative Site 1121
  • Tennessee
    • Brentwood, Tennessee, United States, 37027
      • Forest Investigative Site 1957
    • Fayetteville, Tennessee, United States, 37334
      • Forest Investigative Site 1526
  • Texas
    • Arlington, Texas, United States, 76012
      • Forest Investigative Site 1440
    • Boerne, Texas, United States, 78006
      • Forest Investigative Site 1879
    • Carrollton, Texas, United States, 75007
      • Forest Investigative Site 1861
    • Corsicana, Texas, United States, 75110
      • Forest Investigative Site 1816
    • Dallas, Texas, United States, 75220
      • Forest Investigative Site 1890
    • El Paso, Texas, United States, 79903
      • Forest Investigative Site 1332
    • Fort Worth, Texas, United States, 76104
      • Forest Investigative Site 2012
    • Houston, Texas, United States, 77070
      • Forest Investigative Site 1951
    • Killeen, Texas, United States, 76543
      • Forest Investigative Site 1902
    • Mckinney, Texas, United States, 75069
      • Forest Investigative Site 1091
    • Plano, Texas, United States, 75001
      • Forest Investigative Site 1826
    • San Angelo, Texas, United States, 76904
      • Forest Investigative Site 0526
    • San Antonio, Texas, United States, 78212
      • Forest Investigative Site 1895
  • Utah
    • Salt Lake City, Utah, United States, 84102
      • Forest Investigative Site 1936
  • Vermont
    • South Burlington, Vermont, United States, 25403
      • Forest Investigative Site 1330
  • Virginia
    • Newport News, Virginia, United States, 23606
      • Forest Investigative Site 1945
    • Norfolk, Virginia, United States, 23502
      • Forest Investigative Site 1404
  • Washington
    • Bellingham, Washington, United States, 98225
      • Forest Investigative Site 1120
    • Spokane, Washington, United States, 99202
      • Forest Investigative Site 1977
    • Spokane, Washington, United States, 99204
      • Forest Investigative Site 1878
    • Spokane, Washington, United States, 99216
      • Forest Investigative Site 1573
    • Tacoma, Washington, United States, 98405
      • Forest Investigative Site 0988
    • Tacoma, Washington, United States, 98405
      • Forest Investigative Site 1870
  • West Virginia
    • Morgantown, West Virginia, United States, 26505
      • Forest Investigative Site 1555

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female patients at least 40 years of age
• Current or former cigarette smoker with a cigarette smoking history of at least 10 pack-years
• A diagnosis of stable moderate to severe COPD and stable airway obstruction as defined by the GOLD guidelines and stable airway obstruction. Patients had to have a postbronchodilator FEV1/FVC ratio < 70% at Visit 1 (GOLD, 2010)
• Post-albuterol/salbutamol FEV1 values ≥ 30% and < 80% of predicted value. FEV1 was measured at the Screening Visit (Visit 1) 10 to 15 minutes after inhalation of albuterol/salbutamol. Predicted normal used for calculation purposes were based on National Health and Nutrition Examination Survey III predicted values (Hankinson et al, 1999)
• Able to perform acceptable and repeatable pulmonary function testing for FEV1 according to ATS/ERS criteria (Miller et al, 2005) at Screening Visit (Visit 1) and throughout their participation in the trial
• Negative serum β-human chorionic gonadotropin pregnancy test at Visit 1 and must have been using hormonal contraceptives or a barrier method plus a spermicidal agent; otherwise at least 1-year postmenopausal or surgically sterile, defined as having a hysterectomy or tubal ligation (applied to female patients only)
• Judged by the Principal Investigator to be in otherwise good stable health based on medical history, physical examination, ECGs, and routine laboratory data evaluations
• Patients previously randomized in an aclidinium monotherapy trial were permitted as long as it had been at least 6 months since the completion of their previous trial participation
• Able to understand the study procedures and be willing to participate in the study as indicated by signing the informed consent

Exclusion Criteria:

• Hospitalization for an acute COPD exacerbation within 3 months before Visit 1
• Any respiratory tract infection (including the upper respiratory tract) or COPD exacerbation in the 6 weeks before Visit 1. Patients who developed a respiratory tract infection or COPD exacerbation during the washout or run-in period were discontinued from the study before randomization
• Any clinically significant respiratory conditions other than COPD, including active tuberculosis, history of interstitial lung disease, pulmonary thromboembolic disease, history of α1-antitrypsin deficiency, pulmonary resection, lung volume surgery, or any other thoracic surgery during the past 12 months, history of bronchiectasis secondary to respiratory diseases other than COPD (eg, cystic fibrosis, Kartagener syndrome), post organ transplantation, or expected to require thoracotomy or other lung surgery during the study
• Clinical history suggesting that the patient had asthma as opposed to COPD (Study Physician was to be contacted to discuss eligibility, if necessary)
• Chronic use of oxygen therapy ≥ 15 hours/day
• Body mass index(BMI) ≥ 40 kg/m2
• Patients who intended to start a pulmonary rehabilitation program during the trial were excluded, as well as those who finished or started it within 3 months prior to Screening Visit
• Clinically significant cardiovascular conditions including: myocardial infarction within the previous 6 months; newly diagnosed arrhythmia within the previous 3 months; unstable angina; unstable arrhythmia that had required changes in pharmacological therapy or other intervention within the previous 6 months; the presence of an automated implantable cardioverter-defibrillator; history of thoracic surgery within the past year before screening; hospitalization within the previous 12 months for heart failure of New York Heart Association functional class III (marked limitation of physical activity and only comfortable at rest, less than ordinary activity causes fatigue, palpitation or dyspnea), or class IV (unable to carry out any physical activity without discomfort) (Criteria Committee of the New York Heart Association criteria, 1994)
• Any uncontrolled infection that may have placed the patient at risk resulting from human immunodeficiency virus, active hepatitis and/or patients with diagnosed active tuberculosis
• QTcB > 470 msec in the resting ECGs performed at Screening (Visit 1), as indicated in the centralized ECG vendor generated report. Patients who were on a stable dose of medication that may prolong the QTc, but had a documented, stable, and normal QTc, could have been considered
• QTcB > 470 msec in the resting ECGs performed before randomization at Visit 2, as indicated in the paper tracing generated by the Sponsor-provided ECG equipment
• Clinically relevant abnormalities in the results of the clinical laboratory tests, in ECG parameters other than QTc, or in the physical examination or vital signs at Visit 1 except for those related to COPD
• History of drug or alcohol abuse within the previous 5 years
• Any other serious or uncontrolled physical or mental condition/disease that, as judged by the Investigator, could have placed the patient at higher risk derived from his/her participation in the study, could have confounded the results of the study, or would be likely to have prevented the patient from complying with the requirements of the study or completing the study. If there was a history of such disease, but the condition had been stable for more than 1 year and was judged by the Investigator not to interfere with the patient's participation in the study, the patient may have been included, with the documented approval of the Study Physician
• History of hypersensitivity reaction to inhaled anticholinergics, beta-2 agonists, sympathomimetic amines, or inhaled medication or any component thereof (including report of paradoxical bronchospasm) or a history of acute urinary retention, symptomatic benign prostatic hyperplasia, bladder neck obstruction, or narrow-angle glaucoma. (Note: Patients who had well controlled, stable, asymptomatic benign prostatic hyperplasia were not to be excluded)
• Sitting, resting systolic BP ≥ 160 mm Hg and/or diastolic BP ≥ 100 mm Hg at Visit 1 and Visit 2
• Unable to use a multidose dry-powder inhaler or a pressurized metered-dose inhaler
• Treatment with any other investigational product within 30 days (or 6 half-lives, whichever was longer) before Visit 1
• Previous participation in a clinical trial with aclidinium bromide in an FDC therapy
• Pregnant or breastfeeding
• Current diagnosis of cancer (present in the patient) other than basal or squamous cell skin cancer. Patients who had a history of cancer must have been cleared before Visit 1 (Screening) on a case-by-case basis
• Patients who did not maintain regular day/night, waking/sleeping cycles (eg, night shift workers)
• Patients who intended to use any concomitant medication not permitted by this protocol or who had not undergone the required washout period for a particular prohibited medication (Appendix III of the protocol, which can be found in Appendix 16.1.1 of this report)
• Patients who were unlikely to be compliant with study requirements (eg, take their medication, complete their electronic diaries, attend clinic at the required times)
• Patients who were employees or relatives of employees of the investigative study center, FRI, Almirall, SA, or Pharmaceutical Product Development (PPD, Inc.)
• Patients who had any other conditions that, in the Investigator's opinion, might have indicated the patient to be unsuitable for the study or supported excluding the patient from the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: 5; Placebo	Drug: Placebo; Inhaled dose-matched placebo, twice per day
Experimental: 1; Aclidinium/formoterol Fixed Dose Combination (FDC) 400/12μg	Drug: Aclidinium Bromide/Formoterol Fumarate; Inhaled Aclidinium/formoterol FDC 400/12μg, twice per day; Drug: Aclidinium Bromide/Formoterol Fumarate; Inhaled Aclidinium/formoterol FDC 400/6μg, twice per day
Experimental: 2; Aclidinium/formoterol Fixed Dose Combination (FDC) 400/6μg	Drug: Aclidinium Bromide/Formoterol Fumarate; Inhaled Aclidinium/formoterol FDC 400/12μg, twice per day; Drug: Aclidinium Bromide/Formoterol Fumarate; Inhaled Aclidinium/formoterol FDC 400/6μg, twice per day
Active Comparator: 3; Aclidinium monotherapy 400 μg	Drug: Aclidinium Bromide; Inhaled Aclidinium 400 μg, twice per day
Active Comparator: 4; Formoterol monotherapy 12 μg	Drug: Formoterol Fumarate; Inhaled Formoterol 12 μg, twice per day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change From Baseline in 1-hour Morning Post-dose Forced Expiratory Volume in One Second (FEV1)	Week 24 of treatment
Change From Baseline in Morning Trough Forced Expiratory Volume in One Second (FEV1)	Week 24 of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Transition Dyspnea Index (TDI) Focal Score	The TDI measures the change from baseline in severity of breathlessness in symptomatic patients. The TDI contains a rating for 3 categories (functional impairment, magnitude of task, magnitude of effort).TDI scale ranges from -3 (major deterioration) to +3 (major improvement) including a 0 score to indicate "no change". The 3 categories are added to obtain a focal score ranging from -9 (including 0) to +9.	Week 24 of treatment
Change From Baseline in St George's Respiratory Questionnaire (SGRQ) Total Score	St George's Respiratory Questionnaire (SGRQ) measures COPD-specific health outcomes and consists of 2 parts with 3 dimension scores (a symptom score and an activity and impacts score). SGRQ total score is the sum of these scores and ranges from 0 (best health status) to 100 (worst health status).	Week 24 of treatment

Collaborators and Investigators

• Sponsor: AstraZeneca

Publications and helpful links

General Publications

• 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.
• 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.
• Jones PW, Leidy NK, Hareendran A, Lamarca R, Chuecos F, Garcia Gil E. The effect of aclidinium bromide on daily respiratory symptoms of COPD, measured using the Evaluating Respiratory Symptoms in COPD (E-RS: COPD) diary: pooled analysis of two 6-month Phase III studies. Respir Res. 2016 May 23;17(1):61. doi: 10.1186/s12931-016-0372-1.
• 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.
• D'Urzo AD, Rennard SI, Kerwin EM, Mergel V, Leselbaum AR, Caracta CF; AUGMENT COPD study investigators. Efficacy and safety of fixed-dose combinations of aclidinium bromide/formoterol fumarate: the 24-week, randomized, placebo-controlled AUGMENT COPD study. Respir Res. 2014 Oct 14;15(1):123. doi: 10.1186/s12931-014-0123-0.

Helpful Links

• CSR Synopsis

Study record dates

Study Major Dates

• Study Start: September 1, 2011
• Primary Completion (Actual): February 1, 2013
• Study Completion (Actual): February 1, 2013

Study Registration Dates

• First Submitted: September 19, 2011
• First Submitted That Met QC Criteria: September 19, 2011
• First Posted (Estimate): September 20, 2011

Study Record Updates

• Last Update Posted (Actual): March 23, 2017
• Last Update Submitted That Met QC Criteria: February 2, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Keywords: COPD; Chronic Obstructive Pulmonary Disease; Chronic Bronchitis; Emphysema; Airflow Obstruction, Chronic; Chronic Airflow Obstruction; Chronic Obstructive Airway Disease; Chronic Obstructive Lung Disease
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Adrenergic Agonists; Anticonvulsants; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Bromides; Formoterol Fumarate
• Other Study ID Numbers: LAC-MD-31