Efficacy, Safety, and Tolerability of Aclidinium Bromide in the Treatment of Moderate-to-severe Chronic Obstructive Pulmonary Disease (COPD) (LAS-MD-38) (LAS-MD-38)

A Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Efficacy, Safety, and Tolerability of 2 Doses of Aclidinium Bromide Compared With Placebo for 12 Weeks in Patients With Moderate to Severe, Stable Chronic Obstructive Pulmonary Disease Followed by a 40-Week Evaluation of the Higher Aclidinium Bromide Dose

The purpose of this study is to evaluate the efficacy, safety and tolerability of aclidinium bromide doses compared with placebo in the treatment of moderate to severe, stable chronic obstructive pulmonary disease. The study will be 56 weeks in duration; a 2-week run-in period followed by a 12-week double-blind, placebo-controlled treatment period. This will be followed by an open-label 40-week treatment period and a 2-week follow up phone call. All patients will receive the higher Aclidinium Bromide during the 40-week open label treatment period.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 544
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 4E1
      • Forest Investigative Site 1177
  • Ontario
    • Windsor, Ontario, Canada, N8X 5A6
      • Forest Investigative Site 0969
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35209
      • Forest Investigative Site 1493
    • Birmingham, Alabama, United States, 35233
      • Forest Investigative Site 1419
    • Muscle Shoals, Alabama, United States, 35662
      • Forest Investigative Site 1413
    • Pell City, Alabama, United States, 35128
      • Forest Investigative Site 1353
  • Arizona
    • Phoenix, Arizona, United States, 85018
      • Forest Investigative Site 1379
  • California
    • Fullerton, California, United States, 92835
      • Forest Investigative Site 2065
    • National City, California, United States, 91950
      • Forest Investigative Site 1451
    • Paramount, California, United States, 90723
      • Forest Investigative Site 1388
    • Rolling Hill Estates, California, United States, 90274
      • Forest Investigative Site 1424
    • Sacramento, California, United States, 95817
      • Forest Investigative Site 1427
    • San Diego, California, United States, 92120
      • Forest Investigative Site 2009
    • San Diego, California, United States, 92120
      • Forest Investigative Site 1418
    • Torrance, California, United States, 90505
      • Forest Investigative Site 1374
    • Vista, California, United States, 92083
      • Forest Investigative Site 1331
  • Colorado
    • Golden, Colorado, United States, 80401
      • Forest Investigative Site 1380
    • Pueblo, Colorado, United States, 81001
      • Forest Investigative Site 1447
  • Florida
    • Clearwater, Florida, United States, 33756
      • Forest Investigative Site 1364
    • Edgewater, Florida, United States, 32132
      • Forest Investigative Site 1516
    • Hollywood, Florida, United States, 33021
      • Forest Investigative Site 1403
    • Homestead, Florida, United States, 33032
      • Forest Investigative Site 1485
    • Miami, Florida, United States, 33126
      • Forest Investigative Site 1352
    • Naples, Florida, United States, 34110
      • Forest Investigative Site 1391
    • Port Orange, Florida, United States, 32129
      • Forest Investigative Site 1376
    • South Miami, Florida, United States, 33143
      • Forest Investigative Site 1372
    • Trinity, Florida, United States, 34655
      • Forest Investigative Site 1407
    • Winter Park, Florida, United States, 32789
      • Forest Investigative Site 1185
  • Georgia
    • Atlanta, Georgia, United States, 30328
      • Forest Investigative Site 1386
    • Calhoun, Georgia, United States, 30701
      • Forest Investigative Site 1411
    • Lawrenceville, Georgia, United States, 30046
      • Forest Investigative Site 1528
  • Idaho
    • Coeur d' Alene, Idaho, United States, 83814
      • Forest Investigative Site 0679
  • Illinois
    • Elk Grove Village, Illinois, United States, 60007
      • Forest Investigative Site 1385
    • O'Fallon, Illinois, United States, 62269
      • Forest Investigative Site 1409
  • Indiana
    • Anderson, Indiana, United States, 46011
      • Forest Investigative Site 1479
    • Evansville, Indiana, United States, 47714
      • Forest Investigative Site 2022
    • Indianapolis, Indiana, United States, 46256
      • Forest Investigative Site 1441
    • South Bend, Indiana, United States, 46617
      • Forest Investigative Site 1149
  • Iowa
    • Iowa City, Iowa, United States, 52240
      • Forest Investigative Site 1406
  • Kansas
    • Topeka, Kansas, United States, 66606
      • Forest Investigative Site 1080
  • Kentucky
    • Bowling Green, Kentucky, United States, 42101
      • Forest Investigative Site 2033
    • Hazard, Kentucky, United States, 41701
      • Forest Investigative Site 1090
  • Louisiana
    • New Orleans, Louisiana, United States, 70115
      • Forest Investigative Site 1430
    • New Orleans, Louisiana, United States, 70119
      • Forest Investigative Site 1446
    • Sunset, Louisiana, United States, 70584
      • Forest Investigative Site 1360
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Forest Investigative Site 1412
    • North East, Maryland, United States, 21901
      • Forest Investigative Site 1518
  • Massachusetts
    • Brockton, Massachusetts, United States, 02301
      • Forest Investigative Site 1442
    • Fall River, Massachusetts, United States, 02720
      • Forest Investigative Site 1421
    • North Dartmouth, Massachusetts, United States, 02747
      • Forest Investigative Site 1029
  • Michigan
    • Chelsea, Michigan, United States, 48118
      • Forest Investigative Site 1405
    • Livonia, Michigan, United States, 48152
      • Forest Investigative Site 0889
    • Troy, Michigan, United States, 48085
      • Forest Investigative Site 1487
  • Minnesota
    • Edina, Minnesota, United States, 58435
      • Forest Investigative Site 1128
    • Fridley, Minnesota, United States, 55432
      • Forest Investigative Site 1527
    • Minneapolis, Minnesota, United States, 55403
      • Forest Investigative Site 1124
    • Rochester, Minnesota, United States, 55904
      • Forest Investigative Site 1118
  • Missouri
    • St. Louis, Missouri, United States, 63141
      • Forest Investigative Site 1399
  • Montana
    • Missoula, Montana, United States, 59808
      • Forest Investigative Site 1400
  • Nebraska
    • Bellevue, Nebraska, United States, 68005
      • Forest Investigative Site 1354
    • Bellevue, Nebraska, United States, 68123
      • Forest Investigative Site 1367
    • Fremont, Nebraska, United States, 68025
      • Forest Investigative Site 1476
    • Omaha, Nebraska, United States, 68114
      • Forest Investigative Site 1363
    • Omaha, Nebraska, United States, 68130
      • Forest Investigative Site 1390
    • Omaha, Nebraska, United States, 68134
      • Forest Investigative Site 1422
  • Nevada
    • Henderson, Nevada, United States, 89014
      • Forest Investigative Site 1359
    • Las Vegas, Nevada, United States, 89123
      • Forest Investigative Site 1355
  • New Mexico
    • Albuquerque, New Mexico, United States, 87108
      • Forest Investigative Site 1486
  • New York
    • Larchmont, New York, United States, 10538
      • Forest Investigative Site 1489
    • New York, New York, United States, 10028
      • Forest Investigative Site 1425
    • North Syracuse, New York, United States, 13212
      • Forest Investigative Site 1373
  • North Carolina
    • Charlotte, North Carolina, United States, 28277
      • Forest Investigative Site 1392
    • High Point, North Carolina, United States, 27262
      • Forest Investigative Site 1366
  • Ohio
    • Cincinnati, Ohio, United States, 45227
      • Forest Investigative Site 1136
    • Cincinnati, Ohio, United States, 45245
      • Forest Investigative Site 1371
    • Columbus, Ohio, United States, 43213
      • Forest Investigative Site 1433
    • Columbus, Ohio, United States, 43209
      • Forest Investigative Site 1361
    • Toledo, Ohio, United States, 43608
      • Forest Investigative Site 1530
    • Zanesville, Ohio, United States, 43701
      • Forest Investigative Site 1393
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • Forest Investigative Site 1362
  • Oregon
    • Medford, Oregon, United States, 97504
      • Forest Investigative Site 2043
    • Medford, Oregon, United States, 97504
      • Forest Investigative Site 2018
  • Pennsylvania
    • Collegeville, Pennsylvania, United States, 19426
      • Forest Investigative Site 1377
    • Erie, Pennsylvania, United States, 16508
      • Forest Investigative Site 1423
    • Feasterville, Pennsylvania, United States, 19053
      • Forest Investigative Site 1428
    • Philadelphia, Pennsylvania, United States, 19107
      • Forest Investigative Site 1443
    • Pittsburgh, Pennsylvania, United States, 15221
      • Forest Investigative Site 1510
    • Tipton, Pennsylvania, United States, 16684
      • Forest Investigative Site 1449
  • Rhode Island
    • Johnston, Rhode Island, United States, 02919
      • Forest Investigative Site 1445
    • Lincoln, Rhode Island, United States, 02865
      • Forest Investigative Site 1477
  • South Carolina
    • Columbia, South Carolina, United States, 29201
      • Forest Investigative Site 1144
    • Easley, South Carolina, United States, 29640
      • Forest Investigative Site 1517
    • Grenville, South Carolina, United States, 29615
      • Forest Investigative Site 1506
    • Union, South Carolina, United States, 29379
      • Forest Investigative Site 1450
  • Tennessee
    • Fayetteville, Tennessee, United States, 37337
      • Forest Investigative Site 1526
    • Knoxville, Tennessee, United States, 37909
      • Forest Investigative Site 1356
    • Knoxville, Tennessee, United States, 37920
      • Forest Investigative Site 1417
  • Texas
    • Amarillo, Texas, United States, 79106
      • Forest Investigative Site 1389
    • Arlington, Texas, United States, 76012
      • Forest Investigative Site 1440
    • Austin, Texas, United States, 78756
      • Forest Investigative Site 1494
    • Houston, Texas, United States, 77074
      • Forest Investigative Site 1375
    • Houston, Texas, United States, 77079
      • Forest Investigative Site 1444
    • Houston, Texas, United States, 77083
      • Forest Investigative Site 1401
    • Houston, Texas, United States, 77479
      • Forest Investigative Site 1381
    • Hurst, Texas, United States, 76054
      • Forest Investigative Site 1357
    • Plano, Texas, United States, 75093
      • Forest Investigative Site 1426
    • Tomball, Texas, United States, 77375
      • Forest Investigative Site 1410
  • Virginia
    • Abingdon, Virginia, United States, 24210
      • Forest Investigative Site 1480
    • Lynchburg, Virginia, United States, 24501
      • Forest Investigative Site 1402
    • Norfolk, Virginia, United States, 23502
      • Forest Investigative Site 1404
    • Richmond, Virginia, United States, 23294
      • Forest Investigative Site 1358
  • Washington
    • Tacoma, Washington, United States, 98405
      • Forest Investigative Site 0988

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:

• A diagnosis of stable moderate to severe COPD as defined by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines, 2008; postbronchodilator FEV1/FVC < 70%, and postbronchodilator FEV1 ≥ 30% and < 80% predicted
• Current or former cigarette smokers

Exclusion Criteria:

• Patients who have been hospitalized for an acute COPD exacerbation within 3 months before the first visit
• Respiratory tract infection or COPD exacerbation in the 6 weeks before Visit 1
• Patient with any clinically significant respiratory conditions other than COPD, cardiovascular conditions or mental illness
• History or presence of asthma verified from medical records
• Chronic use of oxygen therapy greater than or equal to 15 hours per day
• Patient with uncontrolled infection due to HIV and/or active hepatitis
• Patients with a history of hypersensitivity reaction to inhaled anticholinergics
• Patients with clinically significant cardiovascular conditions, including myocardial infarction during 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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; Aclidinium bromide 200 μg dose twice per day, inhaled for 12 weeks of treatment At week 12, patients who were on Aclidinium bromide 200 μg will receive open label 400µg aclidinium bromide for 40 weeks	Drug: Aclidinium bromide; Aclidinium bromide 200 μg, oral inhalation twice per day 12 weeks of treatment. At week 12, patients who were on Aclidinium bromide 200 μg will receive open label 400µg aclidinium bromide for 40 weeks of treatment.
Experimental: 2; Aclidinium bromide 400 μg dose twice per day, inhaled for 12 weeks of treatment. At week 12, patients who were on Aclidinium bromide 400 μg will continue to receive open label 400µg aclidinium bromide for 40 weeks	Drug: Aclidinium bromide; Aclidinium bromide 200 μg, oral inhalation twice per day 12 weeks of treatment. At week 12, patients who were on Aclidinium bromide 200 μg will receive open label 400µg aclidinium bromide for 40 weeks of treatment.
Placebo Comparator: 3; Dose-match placebo, oral inhalation twice per day for 12 weeks of treatment. At week 12, patients who were on placebo will receive open label 400µg aclidinium bromide for 40 weeks	Drug: Placebo; Dose-matched placebo, oral inhalation twice per day for 12 weeks. At week 12, patients who were on placebo will receive open label 400 µg aclidinium bromide for 40 weeks of treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A: Morning Predose (Trough) Forced Expiratory Volume in 1 Second (FEV1)	Change from baseline in Trough forced expiratory volume in 1 second before the morning dose of aclidinium bromide, Last Observation Carried Forward (LOCF)	Change from baseline (Week 0) to Week 12
Part B: Morning Predose (Trough) FEV1	Change from Baseline in Morning Pre-dose (trough) Forced Expiratory Volume in 1 Second (FEV1) at Week 52, Lost Observation Carried Forward (LOCF)	Change from baseline (Week 0) to 52 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A: Peak Forced Expiratory Volume in 1 Second (FEV1)	Change from baseline in peak FEV1 at week 12, Last Observation Carried Forward (LOCF)	Change from baseline (Week 0) to Week 12
Part B: Peak FEV1	Change from Baseline in Peak FEV1 (L) at Week 52, Last Observation Carried Forward (LOCF)	Change from baseline (Week 0) to 52 Weeks

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Study Director: Esther Garcia, Ph. D., AstraZeneca

Publications and helpful links

General Publications

• Rennard SI, Scanlon PD, Ferguson GT, Rekeda L, Maurer BT, Garcia Gil E, Caracta CF. ACCORD COPD II: a randomized clinical trial to evaluate the 12-week efficacy and safety of twice-daily aclidinium bromide in chronic obstructive pulmonary disease patients. Clin Drug Investig. 2013 Dec;33(12):893-904. doi: 10.1007/s40261-013-0138-1.

Helpful Links

• las-md-38-synopsis

Study record dates

Study Major Dates

• Study Start: March 1, 2009
• Primary Completion (Actual): June 1, 2011
• Study Completion (Actual): June 1, 2011

Study Registration Dates

• First Submitted: January 7, 2010
• First Submitted That Met QC Criteria: January 7, 2010
• First Posted (Estimate): January 8, 2010

Study Record Updates

• Last Update Posted (Estimate): January 23, 2017
• Last Update Submitted That Met QC Criteria: November 30, 2016
• Last Verified: November 1, 2016

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; Anticonvulsants; Bromides
• Other Study ID Numbers: LAS-MD-38