Efficacy, Safety and Tolerability of Two Fixed Dose Combinations of Aclidinium Bromide/Formoterol Fumarate, Aclidinium Bromide, Formoterol Fumarate and Placebo for 28-Weeks Treatment in Patients With Moderate to Severe, Stable Chronic Obstructive Pulmonary Disease (COPD)

NCT01572792 | Completed Phase 3 Results

• 1 other identifier: LAC-MD-36
• Study Type: interventional
• Target: 921
• Locations: 4 countries
• Sites: 208

Brief Summary

The purpose of this Phase III study is to evaluate the long-term safety and tolerability of two fixed-dose combinations of inhaled aclidinium bromide/formoterol fumarate, aclidinium bromide, formoterol fumarate and placebo in patients with moderate to severe Chronic Obstructive Pulmonary Disease (COPD). Long-term efficacy, pharmacoeconomic and health-related quality of life assessments will also be evaluated. This extension study will include a 28 week treatment period, followed by a four week follow up visit. All patients will remain in the same treatment group as for the lead-in study and continue on one of the four treatment arms or placebo.

Conditions

Chronic Obstructive Pulmonary Disease

Keywords

COPD; Chronic Obstructive Pulmonary Disease; Chronic Bronchitis; Emphysema; Airflow Obstruction, Chronic; Chronic Airflow Obstruction; Chronic Obstructive Airway Disease; Chronic Obstructive Lung Disease

Outcome Measures

Primary Outcomes (1)

• Percentage of Patients to Experience Any Treatment-emergent Adverse Event

  For each safety parameter, the last assessment made before the first dose of investigational product in the lead-in study (LAC MD-31) was used as the baseline for all analyses of that safety parameter in this extension study

  Baseline of lead-in study to follow-up call 14±3 days after last dose of investigational product (up to Week 52)

Secondary Outcomes (3)

• Percentage of Patients to Experience Potentially Clinically Significant Post-baseline Clinical Laboratory Values for Hematology, Chemistry or Urinalysis

  Baseline of lead-in study to end of treatment (up to Week 52)

• Percentage of Patients to Experience a Potentially Significant Post-baseline 12-lead ECG Value

  Baseline of lead-in study to end of treatment (up to Week 52)

• Percentage of Patients to Experience Potentially Clinically Significant Post-baseline Vital Signs (Pulse Rate, Systolic or Diastolic Blood Pressure or Weight)

  Baseline of lead-in study to end of treatment (up to Week 52)

Other Outcomes (4)

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

  Baseline of lead-in study to Week 52 of treatment

• Change From Baseline in Morning Predose (Trough) Forced Expiratory Volume in One Second (FEV1)

  Baseline of lead-in study to Week 52 of treatment

• Transition Dyspnea Index (TDI) Focal Score at End of Study

  Baseline of lead-in study to Week 52 of treatment

Study Arms (5)

1

EXPERIMENTAL

Aclidinium bromide/formoterol Fixed-Dose Combination (FDC) high dose

Drug: Aclidinium bromide/formoterol Fixed-Dose Combination (FDC)

2

EXPERIMENTAL

Aclidinium bromide/formoterol Fixed-Dose Combination (FDC) low dose

Drug: Aclidinium bromide/formoterol Fixed-Dose Combination (FDC)

3

ACTIVE COMPARATOR

Aclidinium bromide 400 μg

Drug: Aclidinium bromide

4

ACTIVE COMPARATOR

Formoterol Fumarate 12 μg

Drug: Formoterol Fumarate

5

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Interventions

Aclidinium bromide/formoterol Fixed-Dose Combination (FDC) DRUG

Inhaled Aclidinium bromide/formoterol Fixed-Dose Combination (FDC) high dose, twice per day

1

Aclidinium bromide DRUG

Inhaled Aclidinium bromide 400 μg, twice per day

3

Formoterol Fumarate DRUG

Inhaled Formoterol Fumarate 12 μg, twice per day

4

Placebo DRUG

Inhaled dose-matched placebo, twice per day

5

Eligibility Criteria

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

You may qualify if:

• Completion of the treatment phase of the lead-in study, LAC-MD-31
• Written informed consent obtained from the patient before the initiation of any study specific procedures
• No medical contraindication as judged by the PI
• Compliance with LAC-MD-31 study procedures and IP dosing.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (208)

Forest Investigative Site 1827

Anniston, Alabama, 36207, United States

Location

Forest Investigative Site 1920

Athens, Alabama, 35611, United States

Location

Forest Investigative Site 1162

Birmingham, Alabama, 35209, United States

Location

Forest Investigative Site 1493

Birmingham, Alabama, 35209, United States

Location

Forest Investigative Site 1937

Birmingham, Alabama, 35216, United States

Location

Forest Investigative Site 1824

Gulf Shores, Alabama, 36542, United States

Location

Forest Investigative Site 2088

Jasper, Alabama, 35501, United States

Location

Forest Investigative Site 1918

Scottsboro, Alabama, 35768, United States

Location

Forest Investigative Site 0909

Glendale, Arizona, 85306, United States

Location

Forest Investigative Site 1379

Phoenix, Arizona, 85018, United States

Location

Forest Investigative Site 1822

Anaheim, California, 92801, United States

Location

Forest Investigative Site 1483

Buena Park, California, 90620, United States

Location

Forest Investigative Site 1156

Fresno, California, 93726, United States

Location

Forest Investigative Site 1871

Lincoln, California, 95648, United States

Location

Forest Investigative Site 1873

Los Angeles, California, 90073, United States

Location

Forest Investigative Site 2064

Riverside, California, 92506, United States

Location

Forest Investigative Site 1427

Sacramento, California, 95817, United States

Location

Forest Investigative Site 1866

Sacramento, California, 95842, United States

Location

Forest Investigative Site 1125

San Diego, California, 92103, United States

Location

Forest Investigative Site 2009

San Diego, California, 92120, United States

Location

Forest Investigative Site 1374

Torrance, California, 90505, United States

Location

Forest Investigative Site 1813

Tustin, California, 92780, United States

Location

Forest Investigative Site 1883

Vista, California, 92083, United States

Location

Forest Investigative Site 1380

Golden, Colorado, 80401, United States

Location

Forest Investigative Site 1137

Pueblo, Colorado, 81001, United States

Location

Forest Investigative Site 1327

Wheat Ridge, Colorado, 80033, United States

Location

Forest Investigative Site 1976

Waterbury, Connecticut, 06708, United States

Location

Forest Investigative Site 1821

Bay Pines, Florida, 33744, United States

Location

Forest Investigative Site 1154

Brandon, Florida, 33511, United States

Location

Forest Investigative Site 1944

Brandon, Florida, 33511, United States

Location

Forest Investigative Site 1364

Clearwater, Florida, 33756, United States

Location

Forest Investigative Site 1152

Clearwater, Florida, 33765, United States

Location

Forest Investigative Site 1875

Clearwater, Florida, 33765, United States

Location

Forest Investigative Site 1811

Covington, Florida, 70433, United States

Location

Forest Investigative Site 0670

DeLand, Florida, 32720, United States

Location

Forest Investigative Site 1516

Edgewater, Florida, 32132, United States

Location

Forest Investigative Site 0990

Fort Lauderdale, Florida, 33316, United States

Location

Forest Investigative Site 1513

Hialeah, Florida, 33012, United States

Location

Forest Investigative Site 1854

Hialeah, Florida, 33012, United States

Location

Forest Investigative Site 1882

Hollywood, Florida, 33024, United States

Location

Forest Investigative Site 1543

Jacksonville, Florida, 32216, United States

Location

Forest Investigative Site 1416

Kissimmee, Florida, 34741, United States

Location

Forest Investigative Site 1167

Melbourne, Florida, 32935, United States

Location

Forest Investigative Site 1432

Miami, Florida, 33143, United States

Location

Forest Investigative Site 1819

Naples, Florida, 34119, United States

Location

Forest Investigative Site 1808

North Miami, Florida, 33179, United States

Location

Forest Investigative Site 1950

Oldsmar, Florida, 34677, United States

Location

Forest Investigative Site 1145

Ormond Beach, Florida, 32174, United States

Location

Forest Investigative Site 1094

Panama City, Florida, 32405, United States

Location

Forest Investigative Site 1803

Pembroke Pines, Florida, 32028, United States

Location

Forest Investigative Site 0974

Pensacola, Florida, 32504, United States

Location

Forest Investigative Site 1817

Sarasota, Florida, 34233, United States

Location

Forest Investigative Site 1874

St. Petersburg, Florida, 33704, United States

Location

Forest Investigative Site 2082

Tamarac, Florida, 33321, United States

Location

Forest Investigative Site 2053

Tampa, Florida, 33603, United States

Location

Forest Investigative Site 2047

Tampa, Florida, 33613, United States

Location

Forest Investigative Site 1185

Winter Park, Florida, 32789, United States

Location

Forest Investigative Site 1860

Winter Park, Florida, 32792, United States

Location

Forest Investigative Site 1900

Atlanta, Georgia, 30312, United States

Location

Forest Investigative Site 0987

Austell, Georgia, 30106, United States

Location

Forest Investigative Site 1828

Canton, Georgia, 30114, United States

Location

Forest Investigative Site 1830

Marietta, Georgia, 30066, United States

Location

Forest Investigative Site 2089

Woodstock, Georgia, 30189, United States

Location

Forest Investigative Site 0679

Coeur d'Alene, Idaho, 83814, United States

Location

Forest Investigative Site 1858

Eagle, Idaho, 83616, United States

Location

Forest Investigative Site 1095

Normal, Illinois, 61761, United States

Location

Forest Investigative Site 1912

Normal, Illinois, 61761, United States

Location

Forest Investigative Site 2051

River Forest, Illinois, 60305, United States

Location

Forest Investigative Site 2033

Bowling Green, Kentucky, 42101, United States

Location

Forest Investigative Site 2085

Fort Mitchell, Kentucky, 41017, United States

Location

Forest Investigative Site 0539

Lexington, Kentucky, 40504, United States

Location

Forest Investigative Site 1478

Louisville, Kentucky, 40217, United States

Location

Forest Investigative Site 1519

Owensboro, Kentucky, 42303, United States

Location

Forest Investigative Site 1430

New Orleans, Louisiana, 70115, United States

Location

Forest Investigative Site 1812

Opelousas, Louisiana, 70570, United States

Location

Forest Investigative Site 1814

Bangor, Maine, 04401, United States

Location

Forest Investigative Site 1924

Baltimore, Maryland, 21237, United States

Location

Forest Investigative Site 1872

Wheaton, Maryland, 20902, United States

Location

Forest Investigative Site 1570

Fall River, Massachusetts, 02720, United States

Location

Forest Investigative Site 1852

Fall River, Massachusetts, 02720, United States

Location

Forest Investigative Site 1431

No. Dartmouth, Massachusetts, 02747, United States

Location

Forest Investigative Site 1892

Ann Arbor, Michigan, 48106, United States

Location

Forest Investigative Site 1342

Stevensville, Michigan, 49127, United States

Location

Forest Investigative Site 1487

Troy, Michigan, 48085, United States

Location

Forest Investigative Site 1128

Edina, Minnesota, 55435, United States

Location

Forest Investigative Site 1527

Fridley, Minnesota, 55432, United States

Location

Forest Investigative Site 2041

Minneapolis, Minnesota, 55402, United States

Location

Forest Investigative Site 1124

Minneapolis, Minnesota, 55407, United States

Location

Forest Investigative Site 1619

Plymouth, Minnesota, 55441, United States

Location

Forest Investigative Site 1118

Rochester, Minnesota, 55905, United States

Location

Forest Investigative Site 1884

Olive Branch, Mississippi, 38654, United States

Location

Forest Investigative Site 1602

Kansas City, Missouri, 64128, United States

Location

Forest Investigative Site 1587

N. Chesterfield, Missouri, 63017, United States

Location

Forest Investigative Site 2079

Saint Charles, Missouri, 63301, United States

Location

Forest Investigative Site 1856

Springfield, Missouri, 65807, United States

Location

Forest Investigative Site 1867

Springfield, Missouri, 65807, United States

Location

Forest Investigative Site 1399

St Louis, Missouri, 63141, United States

Location

Forest Investigative Site 1599

St Louis, Missouri, 63141, United States

Location

Forest Investigative Site 1831

Bozeman, Montana, 59718, United States

Location

Forest Investigative Site 1400

Missoula, Montana, 59808, United States

Location

Forest Investigative Site 1609

Bellevue, Nebraska, 68123, United States

Location

Forest Investigative Site 1948

Fremont, Nebraska, 68025, United States

Location

Forest Investigative Site 1815

Lincoln, Nebraska, 68510, United States

Location

Forest Investigative Site 1363

Omaha, Nebraska, 68114, United States

Location

Forest Investigative Site 1907

Omaha, Nebraska, 68130, United States

Location

Forest Investigative Site 1911

Omaha, Nebraska, 68131, United States

Location

Forest Investigative Site 1908

Omaha, Nebraska, 68134, United States

Location

Forest Investigative Site 1804

Omaha, Nebraska, 68144, United States

Location

Forest Investigative Site 1807

Henderson, Nevada, 89052, United States

Location

Forest Investigative Site 1834

Las Vegas, Nevada, 89128, United States

Location

Forest Investigative Site 1562

Las Vegas, Nevada, 89183, United States

Location

Forest Investigative Site 1559

Cherry Hill, New Jersey, 08003, United States

Location

Forest Investigative Site 1923

Hackensack, New Jersey, 07601, United States

Location

Forest Investigative Site 1949

Albuquerque, New Mexico, 87106, United States

Location

Forest Investigative Site 1151

Great Neck, New York, 11021, United States

Location

Forest Investigative Site 1489

Larchmont, New York, 10538, United States

Location

Forest Investigative Site 550

New York, New York, 10003, United States

Location

Forest Investigative Site 1425

New York, New York, 10028, United States

Location

Forest Investigative Site 2098

Rochester, New York, 14618, United States

Location

Forest Investigative Site 1392

Charlotte, North Carolina, 28277, United States

Location

Forest Investigative Site 2035

Elizabeth City, North Carolina, 27909, United States

Location

Forest Investigative Site 1366

High Point, North Carolina, 27262, United States

Location

Forest Investigative Site 1153

Raleigh, North Carolina, 27607, United States

Location

Forest Investigative Site 1823

Salisbury, North Carolina, 28144, United States

Location

Forest Investigative Site 1891

Cadiz, Ohio, 43907, United States

Location

Forest Investigative Site 1134

Canton, Ohio, 44718, United States

Location

Forest Investigative Site 1885

Cincinnati, Ohio, 45219, United States

Location

Forest Investigative Site 1806

Cincinnati, Ohio, 45231, United States

Location

Forest Investigative Site 2028

Cincinnati, Ohio, 45242, United States

Location

Forest Investigative Site 1903

Cincinnati, Ohio, 45255, United States

Location

Forest Investigative Site 1361

Columbus, Ohio, 43207, United States

Location

Forest Investigative Site 1433

Columbus, Ohio, 43213, United States

Location

Forest Investigative Site 2090

Sylvania, Ohio, 43560, United States

Location

Forest Investigative Site 1530

Toledo, Ohio, 43608, United States

Location

Forest Investigative Site 1393

Zanesville, Ohio, 43701, United States

Location

Forest Investigative Site 1915

Oklahoma City, Oklahoma, 73103, United States

Location

Forest Investigative Site 1889

Bend, Oregon, 97701, United States

Location

Forest Investigative Site 2043

Medford, Oregon, 97504, United States

Location

Forest Investigative Site 1833

Altoona, Pennsylvania, 16601, United States

Location

Forest Investigative Site 1820

Downington, Pennsylvania, 19335, United States

Location

Forest Investigative Site 1423

Erie, Pennsylvania, 16508, United States

Location

Forest Investigative Site 1899

Langhorne, Pennsylvania, 19047, United States

Location

Forest Investigative Site 1443

Philadelphia, Pennsylvania, 19107, United States

Location

Forest Investigative Site 1863

Phoenixville, Pennsylvania, 19460, United States

Location

Forest Investigative Site 1146

Pittsburgh, Pennsylvania, 15243, United States

Location

Forest Investigative Site 1449

Tipton, Pennsylvania, 16684, United States

Location

Forest Investigative Site 1862

Uniontown, Pennsylvania, 15473, United States

Location

Forest Investigative Site 1832

Cumberland, Rhode Island, 02864, United States

Location

Forest Investigative Site 1089

East Providence, Rhode Island, 02914, United States

Location

Forest Investigative Site 2072

Charleston, South Carolina, 29406, United States

Location

Forest Investigative Site 1905

Charleston, South Carolina, 29407, United States

Location

Forest Investigative Site 1802

Charleston, South Carolina, 29412, United States

Location

Forest Investigative Site 1914

Fort Mill, South Carolina, 29707, United States

Location

Forest Investigative Site 1913

Gaffney, South Carolina, 29340, United States

Location

Forest Investigative Site 1121

Spartanburg, South Carolina, 29303, United States

Location

Forest Investigative Site 1957

Brentwood, Tennessee, 37027, United States

Location

Forest Investigative Site 1526

Fayetteville, Tennessee, 37334, United States

Location

Forest Investigative Site 1440

Arlington, Texas, 76012, United States

Location

Forest Investigative Site 1879

Boerne, Texas, 78006, United States

Location

Forest Investigative Site 1861

Carrollton, Texas, 75007, United States

Location

Forest Investigative Site 1816

Corsicana, Texas, 75110, United States

Location

Forest Investigative Site 1890

Dallas, Texas, 75220, United States

Location

Forest Investigative Site 1332

El Paso, Texas, 79903, United States

Location

Forest Investigative Site 2012

Fort Worth, Texas, 76104, United States

Location

Forest Investigative Site 1951

Houston, Texas, 77070, United States

Location

Forest Investigative Site 1091

McKinney, Texas, 75069, United States

Location

Forest Investigative Site 1826

Plano, Texas, 75001, United States

Location

Forest Investigative Site 1895

San Antonio, Texas, 78212, United States

Location

Forest Investigative Site 1936

Salt Lake City, Utah, 84102, United States

Location

Forest Investigative Site 1330

South Burlington, Vermont, 05403, United States

Location

Forest Investigative Site 1945

Newport News, Virginia, 23606, United States

Location

Forest Investigative Site 1404

Norfolk, Virginia, 23502, United States

Location

Forest Investigative Site 1120

Bellingham, Washington, 98225, United States

Location

Forest Investigative Site 1977

Spokane, Washington, 99202, United States

Location

Forest Investigative Site 1878

Spokane, Washington, 99204, United States

Location

Forest Investigative Site 1573

Spokane, Washington, 99216, United States

Location

Forest Investigative Site 0988

Tacoma, Washington, 98405, United States

Location

Forest Investigative Site 1870

Tacoma, Washington, 98405, United States

Location

Forest Investigative Site 1555

Morgantown, West Virginia, 26505, United States

Location

Forest Investigative Site 1991

New Lambton, New South Wales, 2305, Australia

Location

Forest Investigative Site 1987

Redcliffe, Queensland, 4020, Australia

Location

Forest Investigative Site 1973

Woolloongabba, Queensland, 4102, Australia

Location

Forest Investigative Site 2253

Adelaide, South Australia, 5000, Australia

Location

Forest Investigative Site 1981

Bedford Park, South Australia, 5042, Australia

Location

Forest Investigative Site 1990

Daw Park, South Australia, 5041, Australia

Location

Forest Investigative Site 2251

Toorak Gardens, South Australia, 5065, Australia

Location

Forest Investigative Site 2250

Clayton, Victoria, 3168, Australia

Location

Forest Investigative Site 1972

Fitzroy, Victoria, 3065, Australia

Location

Forest Investigative Site 1986

Geelong, Victoria, 3220, Australia

Location

Forest Investigative Site 1985

Parkville, Victoria, 3050, Australia

Location

Forest Investigative Site 1904

Langley, British Columbia, V3A 4H9, Canada

Location

Forest Investigative Site 905

Vancouver, British Columbia, V5Z 1M9, Canada

Location

Forest Investigative Site 0976

Winnipeg, Manitoba, R2K 3S8, Canada

Location

Forest Investigative Site 1877

Sarina, Ontario, N7T 4X3, Canada

Location

Forest Investigative Site 1896

Sarnia, Ontario, N7T 4X3, Canada

Location

Forest Investigative Site 1171

Toronto, Ontario, M5T 3A9, Canada

Location

Forest Investigative Site 2203

Toronto, Ontario, M6H 3M2, Canada

Location

Forest Investigative Site 1952

Montreal, Quebec, H2R 1V6, Canada

Location

Forest Investigative Site 1859

Québec, Quebec, G1V 4M6, Canada

Location

Forest Investigative Site 0943

Saskatoon, Saskatchewan, S7N 0W8, Canada

Location

Forest Investigative Site 1027

Auckland, 1051, New Zealand

Location

Forest Investigative Site 1970

Christchurch, 8011, New Zealand

Location

Forest Investigative Site 1967

Dunedin, 9012, New Zealand

Location

Forest Investigative Site 1964

Dunedin, 9058, New Zealand

Location

Forest Investigative Site 1968

Hamilton, 3240, New Zealand

Location

Forest Investigative Site 1965

Tauranga, 3110, New Zealand

Location

Forest Investigative Site 1980

Tauranga, 3112, New Zealand

Location

Forest Investigative Site 1025

Wellington, 7366, New Zealand

Location

Related Publications (1)

• D'Urzo A, Rennard S, Kerwin E, Donohue JF, Lei A, Molins E, Leselbaum A. A randomised double-blind, placebo-controlled, long-term extension study of the efficacy, safety and tolerability of fixed-dose combinations of aclidinium/formoterol or monotherapy in the treatment of chronic obstructive pulmonary disease. Respir Med. 2017 Apr;125:39-48. doi: 10.1016/j.rmed.2017.02.008. Epub 2017 Feb 16.

  PMID: 28340861 DERIVED

Related Links

• lac-md-36-synopsis

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive; Bronchitis, Chronic; 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; Bronchitis; Respiratory Tract Infections; Infections; Bronchial Diseases

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines

Limitations and Caveats

The objective of this extension study was to assess long-term safety and tolerability. Thus efficacy assessments were considered only supportive to the lead-in study (LAC-MD-31), and were not categorized as primary, secondary, or additional

Results Point of Contact

• Title: Study Director
• Organization: AstraZeneca

ClinicalTrialTransparency@astrazeneca.com

Study Officials

• Esther Garcia, MD

  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: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 4, 2012
• First Posted: April 6, 2012
• Study Start: April 1, 2012
• Primary Completion: June 1, 2013
• Study Completion: June 1, 2013
• Last Updated: April 21, 2017
• Results First Posted: April 21, 2017

Record last verified: 2017-02

Locations

CA (10); NZ (8); AU (11); US (179)