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)
Sponsor
AstraZeneca (Industry)
Overall Status
Completed
CT.gov ID
NCT01572792
Collaborator
(none)
921
208
5
14
4.4
0.3
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
921 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Phase III, Long-term, Randomized, Double-blind, Extension Study of the 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)
Study Start Date
:
Apr 1, 2012
Actual Primary Completion Date
:
Jun 1, 2013
Actual Study Completion Date
:
Jun 1, 2013
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 1 Aclidinium bromide/formoterol Fixed-Dose Combination (FDC) high dose |
Drug: Aclidinium bromide/formoterol Fixed-Dose Combination (FDC)
Inhaled Aclidinium bromide/formoterol Fixed-Dose Combination (FDC) high dose, twice per day
|
| Experimental: 2 Aclidinium bromide/formoterol Fixed-Dose Combination (FDC) low dose |
Drug: Aclidinium bromide/formoterol Fixed-Dose Combination (FDC)
Inhaled Aclidinium bromide/formoterol Fixed-Dose Combination (FDC) low dose, twice per day
|
| Active Comparator: 3 Aclidinium bromide 400 μg |
Drug: Aclidinium bromide
Inhaled Aclidinium bromide 400 μg, twice per day
|
| Active Comparator: 4 Formoterol Fumarate 12 μg |
Drug: Formoterol Fumarate
Inhaled Formoterol Fumarate 12 μg, twice per day
|
| Placebo Comparator: 5 Placebo |
Drug: Placebo
Inhaled dose-matched placebo, twice per day
|
Outcome Measures
Primary Outcome Measures
- Percentage of Patients to Experience Any Treatment-emergent Adverse Event [Baseline of lead-in study to follow-up call 14±3 days after last dose of investigational product (up to Week 52)]
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
Secondary Outcome Measures
- 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)]
Potentially clinically significant change: >1.15 × upper limit of normal (ULN) for absolute cell count of basophils, eosinophils or monocytes, blood alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, total bilirubin, blood urea nitrogen, total cholesterol, creatine kinase, creatinine, gamma glutamyl transferase, lactate dehydrogenase, triglycerides or uric acid <0.85 x lower limit of normal (LLN) or > 1.15 ULN for hematocrit ratio, haemoglobin, lymphocytes or neutrophils absolute cell count, platelet count (thrombocytes), red or white blood cell count, calcium, fasting glucose, phosphorus, total protein, or urinary pH <0.95 x LLN or >1.05 x ULN for chloride, potassium, sodium Urinary glucose ≥0.015, blood or ketones or protein ≥1 or specific gravity >1.1 × ULN The last assessment made before the first dose of investigational product in the lead-in study was used as the baseline for all safety analyses in the extension study
- 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)]
Potentially clinically significant change: Systolic BP ≥180 mmHg and increase ≥20 mmHg from baseline or ≤90 mmHg and decrease ≥20 mmHg from baseline Diastolic BP ≥105 mmHg and increase ≥15 mmHg from baseline or ≤50 mmHg and decrease ≥15 mmHg from baseline Pulse rate ≥110 bpm and increase ≥15% from baseline or ≤50 bpm and decrease ≥15% from baseline Weight increase or decrease ≥7% from baseline The last assessment made before the first dose of investigational product in the lead-in study was used as the baseline for all safety analyses in the extension study
Other Outcome Measures
- 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]
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.
- Change From Baseline in St George's Respiratory Questionnaire (SGRQ) Total Score [Baseline of lead-in study to Week 52 of treatment]
St George's Respiratory Questionnaire (SGRQ) measures COPD-specific health outcomes and consists of 3 dimension scores (symptom, activity and impact). SGRQ total score is the sum of these scores and ranges from 0 (best health status) to 100 (worst health status).
Eligibility Criteria
Criteria
Ages Eligible for Study:
40 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
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.
Exclusion Criteria:
- No specific exclusion criteria
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Forest Investigative Site 1827 | Anniston | Alabama | United States | 36207 |
| 2 | Forest Investigative Site 1920 | Athens | Alabama | United States | 35611 |
| 3 | Forest Investigative Site 1162 | Birmingham | Alabama | United States | 35209 |
| 4 | Forest Investigative Site 1493 | Birmingham | Alabama | United States | 35209 |
| 5 | Forest Investigative Site 1937 | Birmingham | Alabama | United States | 35216 |
| 6 | Forest Investigative Site 1824 | Gulf Shores | Alabama | United States | 36542 |
| 7 | Forest Investigative Site 2088 | Jasper | Alabama | United States | 35501 |
| 8 | Forest Investigative Site 1918 | Scottsboro | Alabama | United States | 35768 |
| 9 | Forest Investigative Site 0909 | Glendale | Arizona | United States | 85306 |
| 10 | Forest Investigative Site 1379 | Phoenix | Arizona | United States | 85018 |
| 11 | Forest Investigative Site 1822 | Anaheim | California | United States | 92801 |
| 12 | Forest Investigative Site 1483 | Buena Park | California | United States | 90620 |
| 13 | Forest Investigative Site 1156 | Fresno | California | United States | 93726 |
| 14 | Forest Investigative Site 1871 | Lincoln | California | United States | 95648 |
| 15 | Forest Investigative Site 1873 | Los Angeles | California | United States | 90073 |
| 16 | Forest Investigative Site 2064 | Riverside | California | United States | 92506 |
| 17 | Forest Investigative Site 1427 | Sacramento | California | United States | 95817 |
| 18 | Forest Investigative Site 1866 | Sacramento | California | United States | 95842 |
| 19 | Forest Investigative Site 1125 | San Diego | California | United States | 92103 |
| 20 | Forest Investigative Site 2009 | San Diego | California | United States | 92120 |
| 21 | Forest Investigative Site 1374 | Torrance | California | United States | 90505 |
| 22 | Forest Investigative Site 1813 | Tustin | California | United States | 92780 |
| 23 | Forest Investigative Site 1883 | Vista | California | United States | 92083 |
| 24 | Forest Investigative Site 1380 | Golden | Colorado | United States | 80401 |
| 25 | Forest Investigative Site 1137 | Pueblo | Colorado | United States | 81001 |
| 26 | Forest Investigative Site 1327 | Wheat Ridge | Colorado | United States | 80033 |
| 27 | Forest Investigative Site 1976 | Waterbury | Connecticut | United States | 06708 |
| 28 | Forest Investigative Site 1821 | Bay Pines | Florida | United States | 33744 |
| 29 | Forest Investigative Site 1154 | Brandon | Florida | United States | 33511 |
| 30 | Forest Investigative Site 1944 | Brandon | Florida | United States | 33511 |
| 31 | Forest Investigative Site 1364 | Clearwater | Florida | United States | 33756 |
| 32 | Forest Investigative Site 1152 | Clearwater | Florida | United States | 33765 |
| 33 | Forest Investigative Site 1875 | Clearwater | Florida | United States | 33765 |
| 34 | Forest Investigative Site 1811 | Covington | Florida | United States | 70433 |
| 35 | Forest Investigative Site 0670 | DeLand | Florida | United States | 32720 |
| 36 | Forest Investigative Site 1516 | Edgewater | Florida | United States | 32132 |
| 37 | Forest Investigative Site 0990 | Fort Lauderdale | Florida | United States | 33316 |
| 38 | Forest Investigative Site 1513 | Hialeah | Florida | United States | 33012 |
| 39 | Forest Investigative Site 1854 | Hialeah | Florida | United States | 33012 |
| 40 | Forest Investigative Site 1882 | Hollywood | Florida | United States | 33024 |
| 41 | Forest Investigative Site 1543 | Jacksonville | Florida | United States | 32216 |
| 42 | Forest Investigative Site 1416 | Kissimmee | Florida | United States | 34741 |
| 43 | Forest Investigative Site 1167 | Melbourne | Florida | United States | 32935 |
| 44 | Forest Investigative Site 1432 | Miami | Florida | United States | 33143 |
| 45 | Forest Investigative Site 1808 | N. Miami | Florida | United States | 33179 |
| 46 | Forest Investigative Site 1819 | Naples | Florida | United States | 34119 |
| 47 | Forest Investigative Site 1950 | Oldsmar | Florida | United States | 34677 |
| 48 | Forest Investigative Site 1145 | Ormond Beach | Florida | United States | 32174 |
| 49 | Forest Investigative Site 1094 | Panama City | Florida | United States | 32405 |
| 50 | Forest Investigative Site 1803 | Pembroke Pines | Florida | United States | 32028 |
| 51 | Forest Investigative Site 0974 | Pensacola | Florida | United States | 32504 |
| 52 | Forest Investigative Site 1817 | Sarasota | Florida | United States | 34233 |
| 53 | Forest Investigative Site 1874 | St. Petersburg | Florida | United States | 33704 |
| 54 | Forest Investigative Site 2082 | Tamarac | Florida | United States | 33321 |
| 55 | Forest Investigative Site 2053 | Tampa | Florida | United States | 33603 |
| 56 | Forest Investigative Site 2047 | Tampa | Florida | United States | 33613 |
| 57 | Forest Investigative Site 1185 | Winter Park | Florida | United States | 32789 |
| 58 | Forest Investigative Site 1860 | Winter Park | Florida | United States | 32792 |
| 59 | Forest Investigative Site 1900 | Atlanta | Georgia | United States | 30312 |
| 60 | Forest Investigative Site 0987 | Austell | Georgia | United States | 30106 |
| 61 | Forest Investigative Site 1828 | Canton | Georgia | United States | 30114 |
| 62 | Forest Investigative Site 1830 | Marietta | Georgia | United States | 30066 |
| 63 | Forest Investigative Site 2089 | Woodstock | Georgia | United States | 30189 |
| 64 | Forest Investigative Site 0679 | Coeur d Alene | Idaho | United States | 83814 |
| 65 | Forest Investigative Site 1858 | Eagle | Idaho | United States | 83616 |
| 66 | Forest Investigative Site 1095 | Normal | Illinois | United States | 61761 |
| 67 | Forest Investigative Site 1912 | Normal | Illinois | United States | 61761 |
| 68 | Forest Investigative Site 2051 | River Forest | Illinois | United States | 60305 |
| 69 | Forest Investigative Site 2033 | Bowling Green | Kentucky | United States | 42101 |
| 70 | Forest Investigative Site 2085 | Fort Mitchell | Kentucky | United States | 41017 |
| 71 | Forest Investigative Site 0539 | Lexington | Kentucky | United States | 40504 |
| 72 | Forest Investigative Site 1478 | Louisville | Kentucky | United States | 40217 |
| 73 | Forest Investigative Site 1519 | Owensboro | Kentucky | United States | 42303 |
| 74 | Forest Investigative Site 1430 | New Orleans | Louisiana | United States | 70115 |
| 75 | Forest Investigative Site 1812 | Opelousas | Louisiana | United States | 70570 |
| 76 | Forest Investigative Site 1814 | Bangor | Maine | United States | 04401 |
| 77 | Forest Investigative Site 1924 | Baltimore | Maryland | United States | 21237 |
| 78 | Forest Investigative Site 1872 | Wheaton | Maryland | United States | 20902 |
| 79 | Forest Investigative Site 1570 | Fall River | Massachusetts | United States | 02720 |
| 80 | Forest Investigative Site 1852 | Fall River | Massachusetts | United States | 02720 |
| 81 | Forest Investigative Site 1431 | No. Dartmouth | Massachusetts | United States | 02747 |
| 82 | Forest Investigative Site 1892 | Ann Arbor | Michigan | United States | 48106 |
| 83 | Forest Investigative Site 1342 | Stevensville | Michigan | United States | 49127 |
| 84 | Forest Investigative Site 1487 | Troy | Michigan | United States | 48085 |
| 85 | Forest Investigative Site 1128 | Edina | Minnesota | United States | 55435 |
| 86 | Forest Investigative Site 1527 | Fridley | Minnesota | United States | 55432 |
| 87 | Forest Investigative Site 2041 | Minneapolis | Minnesota | United States | 55402 |
| 88 | Forest Investigative Site 1124 | Minneapolis | Minnesota | United States | 55407 |
| 89 | Forest Investigative Site 1619 | Plymouth | Minnesota | United States | 55441 |
| 90 | Forest Investigative Site 1118 | Rochester | Minnesota | United States | 55905 |
| 91 | Forest Investigative Site 1884 | Olive Branch | Mississippi | United States | 38654 |
| 92 | Forest Investigative Site 1602 | Kansas City | Missouri | United States | 64128 |
| 93 | Forest Investigative Site 1587 | N. Chesterfield | Missouri | United States | 63017 |
| 94 | Forest Investigative Site 1856 | Springfield | Missouri | United States | 65807 |
| 95 | Forest Investigative Site 1867 | Springfield | Missouri | United States | 65807 |
| 96 | Forest Investigative Site 2079 | St. Charles | Missouri | United States | 63301 |
| 97 | Forest Investigative Site 1399 | St. Louis | Missouri | United States | 63141 |
| 98 | Forest Investigative Site 1599 | St. Louis | Missouri | United States | 63141 |
| 99 | Forest Investigative Site 1831 | Bozeman | Montana | United States | 59718 |
| 100 | Forest Investigative Site 1400 | Missoula | Montana | United States | 59808 |
| 101 | Forest Investigative Site 1609 | Bellevue | Nebraska | United States | 68123 |
| 102 | Forest Investigative Site 1948 | Fremont | Nebraska | United States | 68025 |
| 103 | Forest Investigative Site 1815 | Lincoln | Nebraska | United States | 68510 |
| 104 | Forest Investigative Site 1363 | Omaha | Nebraska | United States | 68114 |
| 105 | Forest Investigative Site 1907 | Omaha | Nebraska | United States | 68130 |
| 106 | Forest Investigative Site 1911 | Omaha | Nebraska | United States | 68131 |
| 107 | Forest Investigative Site 1908 | Omaha | Nebraska | United States | 68134 |
| 108 | Forest Investigative Site 1804 | Omaha | Nebraska | United States | 68144 |
| 109 | Forest Investigative Site 1807 | Henderson | Nevada | United States | 89052 |
| 110 | Forest Investigative Site 1834 | Las Vegas | Nevada | United States | 89128 |
| 111 | Forest Investigative Site 1562 | Las Vegas | Nevada | United States | 89183 |
| 112 | Forest Investigative Site 1559 | Cherry Hill | New Jersey | United States | 08003 |
| 113 | Forest Investigative Site 1923 | Hackensack | New Jersey | United States | 07601 |
| 114 | Forest Investigative Site 1949 | Albuquerque | New Mexico | United States | 87106 |
| 115 | Forest Investigative Site 1151 | Great Neck | New York | United States | 11021 |
| 116 | Forest Investigative Site 1489 | Larchmont | New York | United States | 10538 |
| 117 | Forest Investigative Site 550 | New York | New York | United States | 10003 |
| 118 | Forest Investigative Site 1425 | New York | New York | United States | 10028 |
| 119 | Forest Investigative Site 2098 | Rochester | New York | United States | 14618 |
| 120 | Forest Investigative Site 1392 | Charlotte | North Carolina | United States | 28277 |
| 121 | Forest Investigative Site 2035 | Elizabeth City | North Carolina | United States | 27909 |
| 122 | Forest Investigative Site 1366 | High Point | North Carolina | United States | 27262 |
| 123 | Forest Investigative Site 1153 | Raleigh | North Carolina | United States | 27607 |
| 124 | Forest Investigative Site 1823 | Salisbury | North Carolina | United States | 28144 |
| 125 | Forest Investigative Site 1891 | Cadiz | Ohio | United States | 43907 |
| 126 | Forest Investigative Site 1134 | Canton | Ohio | United States | 44718 |
| 127 | Forest Investigative Site 1885 | Cincinnati | Ohio | United States | 45219 |
| 128 | Forest Investigative Site 1806 | Cincinnati | Ohio | United States | 45231 |
| 129 | Forest Investigative Site 2028 | Cincinnati | Ohio | United States | 45242 |
| 130 | Forest Investigative Site 1903 | Cincinnati | Ohio | United States | 45255 |
| 131 | Forest Investigative Site 1361 | Columbus | Ohio | United States | 43207 |
| 132 | Forest Investigative Site 1433 | Columbus | Ohio | United States | 43213 |
| 133 | Forest Investigative Site 2090 | Sylvania | Ohio | United States | 43560 |
| 134 | Forest Investigative Site 1530 | Toledo | Ohio | United States | 43608 |
| 135 | Forest Investigative Site 1393 | Zanesville | Ohio | United States | 43701 |
| 136 | Forest Investigative Site 1915 | Oklahoma City | Oklahoma | United States | 73103 |
| 137 | Forest Investigative Site 1889 | Bend | Oregon | United States | 97701 |
| 138 | Forest Investigative Site 2043 | Medford | Oregon | United States | 97504 |
| 139 | Forest Investigative Site 1833 | Altoona | Pennsylvania | United States | 16601 |
| 140 | Forest Investigative Site 1820 | Downington | Pennsylvania | United States | 19335 |
| 141 | Forest Investigative Site 1423 | Erie | Pennsylvania | United States | 16508 |
| 142 | Forest Investigative Site 1899 | Langhorne | Pennsylvania | United States | 19047 |
| 143 | Forest Investigative Site 1443 | Philadelphia | Pennsylvania | United States | 19107 |
| 144 | Forest Investigative Site 1863 | Phoenixville | Pennsylvania | United States | 19460 |
| 145 | Forest Investigative Site 1146 | Pittsburgh | Pennsylvania | United States | 15243 |
| 146 | Forest Investigative Site 1449 | Tipton | Pennsylvania | United States | 16684 |
| 147 | Forest Investigative Site 1862 | Uniontown | Pennsylvania | United States | 15473 |
| 148 | Forest Investigative Site 1832 | Cumberland | Rhode Island | United States | 02864 |
| 149 | Forest Investigative Site 1089 | East Providence | Rhode Island | United States | 02914 |
| 150 | Forest Investigative Site 2072 | Charleston | South Carolina | United States | 29406 |
| 151 | Forest Investigative Site 1905 | Charleston | South Carolina | United States | 29407 |
| 152 | Forest Investigative Site 1802 | Charleston | South Carolina | United States | 29412 |
| 153 | Forest Investigative Site 1914 | Fort Mill | South Carolina | United States | 29707 |
| 154 | Forest Investigative Site 1913 | Gaffney | South Carolina | United States | 29340 |
| 155 | Forest Investigative Site 1121 | Spartanburg | South Carolina | United States | 29303 |
| 156 | Forest Investigative Site 1957 | Brentwood | Tennessee | United States | 37027 |
| 157 | Forest Investigative Site 1526 | Fayetteville | Tennessee | United States | 37334 |
| 158 | Forest Investigative Site 1440 | Arlington | Texas | United States | 76012 |
| 159 | Forest Investigative Site 1879 | Boerne | Texas | United States | 78006 |
| 160 | Forest Investigative Site 1861 | Carrollton | Texas | United States | 75007 |
| 161 | Forest Investigative Site 1816 | Corsicana | Texas | United States | 75110 |
| 162 | Forest Investigative Site 1890 | Dallas | Texas | United States | 75220 |
| 163 | Forest Investigative Site 1332 | El Paso | Texas | United States | 79903 |
| 164 | Forest Investigative Site 2012 | Fort Worth | Texas | United States | 76104 |
| 165 | Forest Investigative Site 1951 | Houston | Texas | United States | 77070 |
| 166 | Forest Investigative Site 1091 | McKinney | Texas | United States | 75069 |
| 167 | Forest Investigative Site 1826 | Plano | Texas | United States | 75001 |
| 168 | Forest Investigative Site 1895 | San Antonio | Texas | United States | 78212 |
| 169 | Forest Investigative Site 1936 | Salt Lake City | Utah | United States | 84102 |
| 170 | Forest Investigative Site 1330 | South Burlington | Vermont | United States | 05403 |
| 171 | Forest Investigative Site 1945 | Newport News | Virginia | United States | 23606 |
| 172 | Forest Investigative Site 1404 | Norfolk | Virginia | United States | 23502 |
| 173 | Forest Investigative Site 1120 | Bellingham | Washington | United States | 98225 |
| 174 | Forest Investigative Site 1977 | Spokane | Washington | United States | 99202 |
| 175 | Forest Investigative Site 1878 | Spokane | Washington | United States | 99204 |
| 176 | Forest Investigative Site 1573 | Spokane | Washington | United States | 99216 |
| 177 | Forest Investigative Site 0988 | Tacoma | Washington | United States | 98405 |
| 178 | Forest Investigative Site 1870 | Tacoma | Washington | United States | 98405 |
| 179 | Forest Investigative Site 1555 | Morgantown | West Virginia | United States | 26505 |
| 180 | Forest Investigative Site 1991 | New Lambton | New South Wales | Australia | 2305 |
| 181 | Forest Investigative Site 1987 | Redcliffe | Queensland | Australia | 4020 |
| 182 | Forest Investigative Site 1973 | Woolloongabba | Queensland | Australia | 4102 |
| 183 | Forest Investigative Site 2253 | Adelaide | South Australia | Australia | 5000 |
| 184 | Forest Investigative Site 1981 | Bedford Park | South Australia | Australia | 5042 |
| 185 | Forest Investigative Site 1990 | Daw Park | South Australia | Australia | 5041 |
| 186 | Forest Investigative Site 2251 | Toorak Gardens | South Australia | Australia | 5065 |
| 187 | Forest Investigative Site 2250 | Clayton | Victoria | Australia | 3168 |
| 188 | Forest Investigative Site 1972 | Fitzroy | Victoria | Australia | 3065 |
| 189 | Forest Investigative Site 1986 | Geelong | Victoria | Australia | 3220 |
| 190 | Forest Investigative Site 1985 | Parkville | Victoria | Australia | 3050 |
| 191 | Forest Investigative Site 1904 | Langley | British Columbia | Canada | V3A 4H9 |
| 192 | Forest Investigative Site 905 | Vancouver | British Columbia | Canada | V5Z 1M9 |
| 193 | Forest Investigative Site 0976 | Winnipeg | Manitoba | Canada | R2K 3S8 |
| 194 | Forest Investigative Site 1877 | Sarina | Ontario | Canada | N7T 4X3 |
| 195 | Forest Investigative Site 1896 | Sarnia | Ontario | Canada | N7T 4X3 |
| 196 | Forest Investigative Site 1171 | Toronto | Ontario | Canada | M5T 3A9 |
| 197 | Forest Investigative Site 2203 | Toronto | Ontario | Canada | M6H 3M2 |
| 198 | Forest Investigative Site 1952 | Montreal | Quebec | Canada | H2R 1V6 |
| 199 | Forest Investigative Site 0943 | Saskatoon | Saskatchewan | Canada | S7N 0W8 |
| 200 | Forest Investigative Site 1859 | Quebec | Canada | G1V 4M6 | |
| 201 | Forest Investigative Site 1027 | Auckland | New Zealand | 1051 | |
| 202 | Forest Investigative Site 1970 | Christchurch | New Zealand | 8011 | |
| 203 | Forest Investigative Site 1967 | Dunedin | New Zealand | 9012 | |
| 204 | Forest Investigative Site 1964 | Dunedin | New Zealand | 9058 | |
| 205 | Forest Investigative Site 1968 | Hamilton | New Zealand | 3240 | |
| 206 | Forest Investigative Site 1965 | Tauranga | New Zealand | 3110 | |
| 207 | Forest Investigative Site 1980 | Tauranga | New Zealand | 3112 | |
| 208 | Forest Investigative Site 1025 | Wellington | New Zealand | 7366 |
Sponsors and Collaborators
- AstraZeneca
Investigators
- Study Director: Esther Garcia, MD, AstraZeneca
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.Responsible Party:
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01572792
Other Study ID Numbers:
- LAC-MD-36
First Posted:
Apr 6, 2012
Last Update Posted:
Apr 21, 2017
Last Verified:
Feb 1, 2017
Keywords provided by AstraZeneca
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | This study was conducted at 169 study centers, 160 in the United States, and 9 in Canada. The first patient was screened in April 2012 and the last patient visit was in June 2013 |
|---|---|
| Pre-assignment Detail | This was a double-blind, placebo- and active-controlled, 28-week treatment, extension study of the lead-in study, Study LAC-MD-31 Those patients who chose to continue the treatment in the extension study and met the eligibility for the extension study remained on the same treatment as they were randomized to in the lead-in study |
| Arm/Group Title | Placebo | Aclidinium/Formoterol 400/12 μg | Aclidinium/Formoterol 400/6 μg | Aclidinium 400 μg | Formoterol 12 μg |
|---|---|---|---|---|---|
| Arm/Group Description | Placebo administered BID by inhalation | Aclidinium bromide 400 μg + formoterol fumurate 12 μg fixed dose combination (FDC) administered BID by inhalation | Aclidinium bromide 400 μg + formoterol fumurate 6 μg fixed dose combination (FDC) administered BID by inhalation | Aclidinium bromide 400 μg administered BID by inhalation | Formoterol fumurate 12 μg administered BID by inhalation |
| Period Title: Lead-in Study | |||||
| STARTED | 337 | 338 | 338 | 340 | 339 |
| COMPLETED | 236 | 272 | 276 | 268 | 270 |
| NOT COMPLETED | 101 | 66 | 62 | 72 | 69 |
| Period Title: Lead-in Study | |||||
| STARTED | 146 | 184 | 205 | 194 | 192 |
| COMPLETED | 121 | 155 | 179 | 165 | 160 |
| NOT COMPLETED | 25 | 29 | 26 | 29 | 32 |
Baseline Characteristics
| Arm/Group Title | Placebo | Aclidinium/Formoterol 400/12 μg | Aclidinium/Formoterol 400/6 μg | Aclidinium 400 μg | Formoterol 12 μg | Total |
|---|---|---|---|---|---|---|
| Arm/Group Description | Placebo administered BID by inhalation | Aclidinium bromide 400 μg + formoterol fumurate 12 μg fixed dose combination (FDC) administered BID by inhalation | Aclidinium bromide 400 μg + formoterol fumurate 6 μg fixed dose combination (FDC) administered BID by inhalation | Aclidinium bromide 400 μg administered BID by inhalation | Formoterol fumurate 12 μg administered BID by inhalation | Total of all reporting groups |
| Overall Participants | 146 | 182 | 204 | 194 | 192 | 918 |
| Age (Years) [Mean (Standard Deviation) ] | ||||||
| Mean (Standard Deviation) [Years] |
63.2
(8.6)
|
63.7
(9.1)
|
63.6
(9.2)
|
62.9
(8.3)
|
62.8
(8.7)
|
63.2
(8.8)
|
| Sex: Female, Male (Count of Participants) | ||||||
| Female |
65
44.5%
|
94
51.6%
|
84
41.2%
|
90
46.4%
|
102
53.1%
|
435
47.4%
|
| Male |
81
55.5%
|
88
48.4%
|
120
58.8%
|
104
53.6%
|
90
46.9%
|
483
52.6%
|
Outcome Measures
| Title | Percentage of Patients to Experience Any Treatment-emergent Adverse Event |
|---|---|
| Description | 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 |
| Time Frame | Baseline of lead-in study to follow-up call 14±3 days after last dose of investigational product (up to Week 52) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Extension Safety Population defined as all patients from the lead-in study (LAC-MD-31) who signed informed consent at Visit 1 of this extension study (last visit of the lead-in study) and who took at least 1 dose of double-blind investigational product in this extension study |
| Arm/Group Title | Placebo | Aclidinium/Formmoterol 400/12 μg | Aclidinium/Formoterol 400/6 μg | Aclidinium 400 μg | Formoterol 12 μg |
|---|---|---|---|---|---|
| Arm/Group Description | Placebo administered BID by inhalation | Aclidinium bromide 400 μg + formoterol fumurate 12 μg fixed dose combination (FDC) administered BID by inhalation | Aclidinium bromide 400 μg + formoterol fumurate 6 μg fixed dose combination (FDC) administered BID by inhalation | Aclidinium bromide 400 μg administered BID by inhalation | Formoterol fumurate 12 μg administered BID by inhalation |
| Measure Participants | 146 | 182 | 204 | 194 | 192 |
| Number [Percentage of participants] |
56.8
38.9%
|
65.9
36.2%
|
61.3
30%
|
67.5
34.8%
|
64.6
33.6%
|
| Title | Percentage of Patients to Experience Potentially Clinically Significant Post-baseline Clinical Laboratory Values for Hematology, Chemistry or Urinalysis |
|---|---|
| Description | Potentially clinically significant change: >1.15 × upper limit of normal (ULN) for absolute cell count of basophils, eosinophils or monocytes, blood alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, total bilirubin, blood urea nitrogen, total cholesterol, creatine kinase, creatinine, gamma glutamyl transferase, lactate dehydrogenase, triglycerides or uric acid <0.85 x lower limit of normal (LLN) or > 1.15 ULN for hematocrit ratio, haemoglobin, lymphocytes or neutrophils absolute cell count, platelet count (thrombocytes), red or white blood cell count, calcium, fasting glucose, phosphorus, total protein, or urinary pH <0.95 x LLN or >1.05 x ULN for chloride, potassium, sodium Urinary glucose ≥0.015, blood or ketones or protein ≥1 or specific gravity >1.1 × ULN The last assessment made before the first dose of investigational product in the lead-in study was used as the baseline for all safety analyses in the extension study |
| Time Frame | Baseline of lead-in study to end of treatment (up to Week 52) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Extension Safety Population defined as all patients from the lead-in study (LAC-MD-31) who signed informed consent at Visit 1 of this extension study (last visit of the lead-in study) and who took at least 1 dose of double-blind investigational product in this extension study |
| Arm/Group Title | Placebo | Aclidinium/Formmoterol 400/12 μg | Aclidinium/Formoterol 400/6 μg | Aclidinium 400 μg | Formoterol 12 μg |
|---|---|---|---|---|---|
| Arm/Group Description | Placebo administered BID by inhalation | Aclidinium bromide 400 μg + formoterol fumurate 12 μg fixed dose combination (FDC) administered BID by inhalation | Aclidinium bromide 400 μg + formoterol fumurate 6 μg fixed dose combination (FDC) administered BID by inhalation | Aclidinium bromide 400 μg administered BID by inhalation | Formoterol fumurate 12 μg administered BID by inhalation |
| Measure Participants | 146 | 182 | 204 | 194 | 192 |
| Number [Percentage of participants] |
32.9
22.5%
|
41.2
22.6%
|
35.3
17.3%
|
32.5
16.8%
|
38.5
20.1%
|
| Title | Percentage of Patients to Experience a Potentially Significant Post-baseline 12-lead ECG Value |
|---|---|
| Description | |
| Time Frame | Baseline of lead-in study to end of treatment (up to Week 52) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Extension Safety Population defined as all patients from the lead-in study (LAC-MD-31) who signed informed consent at Visit 1 of this extension study (last visit of the lead-in study) and who took at least 1 dose of double-blind investigational product in this extension study |
| Arm/Group Title | Placebo | Aclidinium/Formmoterol 400/12 μg | Aclidinium/Formoterol 400/6 μg | Aclidinium 400 μg | Formoterol 12 μg |
|---|---|---|---|---|---|
| Arm/Group Description | Placebo administered BID by inhalation | Aclidinium bromide 400 μg + formoterol fumurate 12 μg fixed dose combination (FDC) administered BID by inhalation | Aclidinium bromide 400 μg + formoterol fumurate 6 μg fixed dose combination (FDC) administered BID by inhalation | Aclidinium bromide 400 μg administered BID by inhalation | Formoterol fumurate 12 μg administered BID by inhalation |
| Measure Participants | 146 | 182 | 204 | 194 | 192 |
| QT interval change from baseline >30 msec |
53.4
36.6%
|
53.8
29.6%
|
55.9
27.4%
|
60.4
31.1%
|
48.4
25.2%
|
| QT interval >480 msec |
3.4
2.3%
|
3.8
2.1%
|
2.9
1.4%
|
2.6
1.3%
|
4.7
2.4%
|
| QTcB change from baseline >30 msec |
36.3
24.9%
|
37.0
20.3%
|
39.7
19.5%
|
35.6
18.4%
|
38.4
20%
|
| QTcB >480 msec |
7.5
5.1%
|
8.3
4.6%
|
9.8
4.8%
|
5.7
2.9%
|
8.4
4.4%
|
| QTcF change from baseline >30 msec |
27.4
18.8%
|
28.7
15.8%
|
30.4
14.9%
|
27.8
14.3%
|
30.2
15.7%
|
| QTcF >480 msec |
2.1
1.4%
|
0.6
0.3%
|
1.0
0.5%
|
0.5
0.3%
|
2.6
1.4%
|
| QRS interval ≥100 msec & ≥25% increase |
6.2
4.2%
|
6.6
3.6%
|
3.9
1.9%
|
2.6
1.3%
|
4.7
2.4%
|
| PR interval ≥200 msec & ≥25% increase |
2.8
1.9%
|
2.2
1.2%
|
1.0
0.5%
|
3.1
1.6%
|
1.6
0.8%
|
| Heart rate ≥110 bpm & ≥15% increase from baseline |
0.7
0.5%
|
2.7
1.5%
|
1.0
0.5%
|
1.0
0.5%
|
2.1
1.1%
|
| Heart rate ≤50 bpm & ≥15% decrease from baseline |
11.0
7.5%
|
6.0
3.3%
|
8.3
4.1%
|
7.2
3.7%
|
4.7
2.4%
|
| Title | Change From Baseline in 1-hour Morning Post-dose Forced Expiratory Volume in One Second (FEV1) |
|---|---|
| Description | |
| Time Frame | Baseline of lead-in study to Week 52 of treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Combined intent to treat (ITT) Population defined as all patients randomized to a treatment group who took at least 1 dose of double-blind investigational product in the lead-in study (LAC-MD-31) and who had a baseline assessment and at least 1 post-baseline assessment of forced expiratory volume in 1 second (FEV1) in LAC-MD-31 |
| Arm/Group Title | Placebo | Aclidinium/Formoterol 400/12 μg | Aclidinium/Formoterol 400/6 μg | Aclidinium 400 μg | Formoterol 12 μg |
|---|---|---|---|---|---|
| Arm/Group Description | Placebo administered BID by inhalation | Aclidinium bromide 400 μg + formoterol fumurate 12 μg fixed dose combination (FDC) administered BID by inhalation | Aclidinium bromide 400 μg + formoterol fumurate 6 μg fixed dose combination (FDC) administered BID by inhalation | Aclidinium bromide 400 μg administered BID by inhalation | Formoterol fumurate 12 μg administered BID by inhalation |
| Measure Participants | 331 | 335 | 333 | 337 | 332 |
| Least Squares Mean (Standard Error) [Liters] |
-0.086
(0.017)
|
0.198
(0.015)
|
0.166
(0.015)
|
0.112
(0.015)
|
0.109
(0.015)
|
| Title | Change From Baseline in Morning Predose (Trough) Forced Expiratory Volume in One Second (FEV1) |
|---|---|
| Description | |
| Time Frame | Baseline of lead-in study to Week 52 of treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Combined intent to treat (ITT) Population defined as all patients randomized to a treatment group who took at least 1 dose of double-blind investigational product in the lead-in study (LAC-MD-31) and who had a baseline assessment and at least 1 post-baseline assessment of forced expiratory volume in 1 second (FEV1) in LAC-MD-31 |
| Arm/Group Title | Placebo | Aclidinium/Formoterol 400/12 μg | Aclidinium/Formoterol 400/6 μg | Aclidinium 400 μg | Formoterol 12 μg |
|---|---|---|---|---|---|
| Arm/Group Description | Placebo administered BID by inhalation | Aclidinium bromide 400 μg + formoterol fumurate 12 μg fixed dose combination (FDC) administered BID by inhalation | Aclidinium bromide 400 μg + formoterol fumurate 6 μg fixed dose combination (FDC) administered BID by inhalation | Aclidinium bromide 400 μg administered BID by inhalation | Formoterol fumurate 12 μg administered BID by inhalation |
| Measure Participants | 331 | 335 | 333 | 337 | 332 |
| Least Squares Mean (Standard Error) [Liters] |
-0.101
(0.017)
|
0.038
(0.015)
|
0.005
(0.015)
|
0.030
(0.015)
|
0.004
(0.015)
|
| Title | Transition Dyspnea Index (TDI) Focal Score at End of Study |
|---|---|
| Description | 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. |
| Time Frame | Baseline of lead-in study to Week 52 of treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Combined intent to treat (ITT) Population defined as all patients randomized to a treatment group who took at least 1 dose of double-blind investigational product in the lead-in study (LAC-MD-31) and who had a baseline assessment and at least 1 post-baseline assessment of forced expiratory volume in 1 second (FEV1) in LAC-MD-31 |
| Arm/Group Title | Placebo | Aclidinium/Formoterol 400/12 μg | Aclidinium/Formoterol 400/6 μg | Aclidinium 400 μg | Formoterol 12 μg |
|---|---|---|---|---|---|
| Arm/Group Description | Placebo administered BID by inhalation | Aclidinium bromide 400 μg + formoterol fumurate 12 μg fixed dose combination (FDC) administered BID by inhalation | Aclidinium bromide 400 μg + formoterol fumurate 6 μg fixed dose combination (FDC) administered BID by inhalation | Aclidinium bromide 400 μg administered BID by inhalation | Formoterol fumurate 12 μg administered BID by inhalation |
| Measure Participants | 331 | 335 | 333 | 337 | 332 |
| Least Squares Mean (Standard Error) [Scores on a scale] |
0.731
(0.277)
|
1.812
(0.251)
|
1.742
(0.235)
|
1.596
(0.241)
|
1.324
(0.246)
|
| Title | Change From Baseline in St George's Respiratory Questionnaire (SGRQ) Total Score |
|---|---|
| Description | St George's Respiratory Questionnaire (SGRQ) measures COPD-specific health outcomes and consists of 3 dimension scores (symptom, activity and impact). SGRQ total score is the sum of these scores and ranges from 0 (best health status) to 100 (worst health status). |
| Time Frame | Baseline of lead-in study to Week 52 of treatment |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Combined intent to treat (ITT) Population defined as all patients randomized to a treatment group who took at least 1 dose of double-blind investigational product in the lead-in study (LAC-MD-31) and who had a baseline assessment and at least 1 post-baseline assessment of forced expiratory volume in 1 second (FEV1) in LAC-MD-31 |
| Arm/Group Title | Placebo | Aclidinium/Formoterol 400/12 μg | Aclidinium/Formoterol 400/6 μg | Aclidinium 400 μg | Formoterol 12 μg |
|---|---|---|---|---|---|
| Arm/Group Description | Placebo administered BID by inhalation | Aclidinium bromide 400 μg + formoterol fumurate 12 μg fixed dose combination (FDC) administered BID by inhalation | Aclidinium bromide 400 μg + formoterol fumurate 6 μg fixed dose combination (FDC) administered BID by inhalation | Aclidinium bromide 400 μg administered BID by inhalation | Formoterol fumurate 12 μg administered BID by inhalation |
| Measure Participants | 331 | 335 | 333 | 337 | 332 |
| Least Squares Mean (Standard Error) [Scores on a scale] |
-1.862
(0.945)
|
-3.646
(0.861)
|
-5.527
(0.819)
|
-4.306
(0.847)
|
-4.059
(0.853)
|
| Title | Percentage of Patients to Experience Potentially Clinically Significant Post-baseline Vital Signs (Pulse Rate, Systolic or Diastolic Blood Pressure or Weight) |
|---|---|
| Description | Potentially clinically significant change: Systolic BP ≥180 mmHg and increase ≥20 mmHg from baseline or ≤90 mmHg and decrease ≥20 mmHg from baseline Diastolic BP ≥105 mmHg and increase ≥15 mmHg from baseline or ≤50 mmHg and decrease ≥15 mmHg from baseline Pulse rate ≥110 bpm and increase ≥15% from baseline or ≤50 bpm and decrease ≥15% from baseline Weight increase or decrease ≥7% from baseline The last assessment made before the first dose of investigational product in the lead-in study was used as the baseline for all safety analyses in the extension study |
| Time Frame | Baseline of lead-in study to end of treatment (up to Week 52) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Extension Safety Population defined as all patients from the lead-in study (LAC-MD-31) who signed informed consent at Visit 1 of this extension study (last visit of the lead-in study) and who took at least 1 dose of double-blind investigational product in this extension study |
| Arm/Group Title | Placebo | Aclidinium/Formmoterol 400/12 μg | Aclidinium/Formoterol 400/6 μg | Aclidinium 400 μg | Formoterol 12 μg |
|---|---|---|---|---|---|
| Arm/Group Description | Placebo administered BID by inhalation | Aclidinium bromide 400 μg + formoterol fumurate 12 μg fixed dose combination (FDC) administered BID by inhalation | Aclidinium bromide 400 μg + formoterol fumurate 6 μg fixed dose combination (FDC) administered BID by inhalation | Aclidinium bromide 400 μg administered BID by inhalation | Formoterol fumurate 12 μg administered BID by inhalation |
| Measure Participants | 146 | 182 | 204 | 194 | 192 |
| Number [Percentage of participants] |
27.4
18.8%
|
24.2
13.3%
|
18.6
9.1%
|
22.2
11.4%
|
24.5
12.8%
|
Adverse Events
| Time Frame | Follow-up call 14±3 days after end of treatment (Week 28±5 days) | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | The Extension Safety Population defined as all patients from the lead-in study (LAC-MD-31) who signed informed consent at Visit 1 of this extension study (last visit of the lead-in study) and who took at least 1 dose of double-blind investigational product in this extension study | |||||||||
| Arm/Group Title | Placebo | Aclidinium/Formoterol 400/12 μg | Aclidinium/Formoterol 400/6 μg | Aclidinium 400 μg | Formoterol 12 μg | |||||
| Arm/Group Description | Placebo administered BID by inhalation | Aclidinium bromide 400 μg + formoterol fumurate 12 μg fixed dose combination (FDC) administered BID by inhalation | Aclidinium bromide 400 μg + formoterol fumurate 6 μg fixed dose combination (FDC) administered BID by inhalation | Aclidinium bromide 400 μg administered BID by inhalation | Formoterol fumurate 12 μg administered BID by inhalation | |||||
All Cause Mortality |
||||||||||
| Placebo | Aclidinium/Formoterol 400/12 μg | Aclidinium/Formoterol 400/6 μg | Aclidinium 400 μg | Formoterol 12 μg | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | |||||
Serious Adverse Events |
||||||||||
| Placebo | Aclidinium/Formoterol 400/12 μg | Aclidinium/Formoterol 400/6 μg | Aclidinium 400 μg | Formoterol 12 μg | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 10/146 (6.8%) | 14/182 (7.7%) | 14/204 (6.9%) | 15/194 (7.7%) | 14/192 (7.3%) | |||||
| Blood and lymphatic system disorders | ||||||||||
| Anaemia | 1/146 (0.7%) | 0/182 (0%) | 0/204 (0%) | 0/194 (0%) | 0/192 (0%) | |||||
| Haemorrhagic anaemia | 0/146 (0%) | 0/182 (0%) | 0/204 (0%) | 0/194 (0%) | 1/192 (0.5%) | |||||
| Pancytopenia | 0/146 (0%) | 1/182 (0.5%) | 0/204 (0%) | 0/194 (0%) | 0/192 (0%) | |||||
| Cardiac disorders | ||||||||||
| Atrioventricular block second degree | 0/146 (0%) | 0/182 (0%) | 0/204 (0%) | 0/194 (0%) | 1/192 (0.5%) | |||||
| Palpitations | 0/146 (0%) | 0/182 (0%) | 0/204 (0%) | 1/194 (0.5%) | 0/192 (0%) | |||||
| Coronary artery disease | 1/146 (0.7%) | 0/182 (0%) | 0/204 (0%) | 0/194 (0%) | 0/192 (0%) | |||||
| Acute myocardial infarction | 0/146 (0%) | 0/182 (0%) | 1/204 (0.5%) | 0/194 (0%) | 0/192 (0%) | |||||
| Angina pectoris | 0/146 (0%) | 0/182 (0%) | 1/204 (0.5%) | 0/194 (0%) | 0/192 (0%) | |||||
| Myocardial infarction | 1/146 (0.7%) | 0/182 (0%) | 0/204 (0%) | 2/194 (1%) | 1/192 (0.5%) | |||||
| Pericardial effusion | 0/146 (0%) | 0/182 (0%) | 0/204 (0%) | 1/194 (0.5%) | 0/192 (0%) | |||||
| Arrhythmia | 1/146 (0.7%) | 0/182 (0%) | 0/204 (0%) | 0/194 (0%) | 0/192 (0%) | |||||
| Atrial fibrillation | 0/146 (0%) | 0/182 (0%) | 1/204 (0.5%) | 0/194 (0%) | 0/192 (0%) | |||||
| Sick sinus syndrome | 1/146 (0.7%) | 0/182 (0%) | 0/204 (0%) | 0/194 (0%) | 0/192 (0%) | |||||
| Cardiac arrest | 0/146 (0%) | 1/182 (0.5%) | 0/204 (0%) | 0/194 (0%) | 0/192 (0%) | |||||
| Cardio-respiratory arrest | 0/146 (0%) | 0/182 (0%) | 1/204 (0.5%) | 0/194 (0%) | 0/192 (0%) | |||||
| Gastrointestinal disorders | ||||||||||
| Colitis ulcerative | 0/146 (0%) | 1/182 (0.5%) | 0/204 (0%) | 0/194 (0%) | 0/192 (0%) | |||||
| Gastritis | 0/146 (0%) | 0/182 (0%) | 1/204 (0.5%) | 0/194 (0%) | 0/192 (0%) | |||||
| Constipation | 0/146 (0%) | 1/182 (0.5%) | 0/204 (0%) | 0/194 (0%) | 0/192 (0%) | |||||
| Enterocolitis | 0/146 (0%) | 1/182 (0.5%) | 0/204 (0%) | 0/194 (0%) | 0/192 (0%) | |||||
| Lower gastrointestinal haemorrhage | 0/146 (0%) | 1/182 (0.5%) | 0/204 (0%) | 0/194 (0%) | 0/192 (0%) | |||||
| Gastrointestinal haemorrhage | 0/146 (0%) | 0/182 (0%) | 1/204 (0.5%) | 0/194 (0%) | 0/192 (0%) | |||||
| General disorders | ||||||||||
| Asthenia | 0/146 (0%) | 0/182 (0%) | 1/204 (0.5%) | 0/194 (0%) | 0/192 (0%) | |||||
| Death | 1/146 (0.7%) | 1/182 (0.5%) | 0/204 (0%) | 0/194 (0%) | 0/192 (0%) | |||||
| Drug withdrawal syndrome | 0/146 (0%) | 1/182 (0.5%) | 0/204 (0%) | 0/194 (0%) | 0/192 (0%) | |||||
| Infections and infestations | ||||||||||
| Diverticulitis | 1/146 (0.7%) | 0/182 (0%) | 0/204 (0%) | 0/194 (0%) | 2/192 (1%) | |||||
| Cellulitis | 0/146 (0%) | 0/182 (0%) | 1/204 (0.5%) | 0/194 (0%) | 2/192 (1%) | |||||
| Postoperative wound infection | 0/146 (0%) | 1/182 (0.5%) | 0/204 (0%) | 0/194 (0%) | 0/192 (0%) | |||||
| Device related infection | 0/146 (0%) | 0/182 (0%) | 0/204 (0%) | 1/194 (0.5%) | 0/192 (0%) | |||||
| Influenza | 0/146 (0%) | 0/182 (0%) | 0/204 (0%) | 1/194 (0.5%) | 0/192 (0%) | |||||
| Lobar pneumonia | 0/146 (0%) | 0/182 (0%) | 1/204 (0.5%) | 1/194 (0.5%) | 0/192 (0%) | |||||
| Pneumonia | 0/146 (0%) | 0/182 (0%) | 3/204 (1.5%) | 2/194 (1%) | 0/192 (0%) | |||||
| Sepsis | 0/146 (0%) | 0/182 (0%) | 1/204 (0.5%) | 1/194 (0.5%) | 0/192 (0%) | |||||
| Urinary tract infection | 0/146 (0%) | 1/182 (0.5%) | 0/204 (0%) | 0/194 (0%) | 0/192 (0%) | |||||
| Pneumonia viral | 0/146 (0%) | 1/182 (0.5%) | 0/204 (0%) | 0/194 (0%) | 0/192 (0%) | |||||
| Bronchitis viral | 0/146 (0%) | 0/182 (0%) | 0/204 (0%) | 0/194 (0%) | 1/192 (0.5%) | |||||
| Injury, poisoning and procedural complications | ||||||||||
| Fibula fracture | 0/146 (0%) | 0/182 (0%) | 0/204 (0%) | 0/194 (0%) | 1/192 (0.5%) | |||||
| Hip fracture | 0/146 (0%) | 0/182 (0%) | 0/204 (0%) | 1/194 (0.5%) | 0/192 (0%) | |||||
| Tibia fracture | 0/146 (0%) | 0/182 (0%) | 0/204 (0%) | 0/194 (0%) | 1/192 (0.5%) | |||||
| Post laminectomy syndrome | 0/146 (0%) | 0/182 (0%) | 0/204 (0%) | 0/194 (0%) | 1/192 (0.5%) | |||||
| Fall | 0/146 (0%) | 1/182 (0.5%) | 1/204 (0.5%) | 0/194 (0%) | 0/192 (0%) | |||||
| Accidental overdose | 0/146 (0%) | 1/182 (0.5%) | 0/204 (0%) | 0/194 (0%) | 0/192 (0%) | |||||
| Pelvic fracture | 0/146 (0%) | 0/182 (0%) | 1/204 (0.5%) | 0/194 (0%) | 0/192 (0%) | |||||
| Ulna fracture | 0/146 (0%) | 0/182 (0%) | 0/204 (0%) | 1/194 (0.5%) | 0/192 (0%) | |||||
| Investigations | ||||||||||
| International normalised ratio increased | 0/146 (0%) | 0/182 (0%) | 1/204 (0.5%) | 0/194 (0%) | 0/192 (0%) | |||||
| Electrocardiogram abnormal | 1/146 (0.7%) | 1/182 (0.5%) | 0/204 (0%) | 0/194 (0%) | 0/192 (0%) | |||||
| Metabolism and nutrition disorders | ||||||||||
| Diabetes mellitus | 0/146 (0%) | 0/182 (0%) | 0/204 (0%) | 0/194 (0%) | 1/192 (0.5%) | |||||
| Hypoglycaemia | 1/146 (0.7%) | 0/182 (0%) | 0/204 (0%) | 0/194 (0%) | 0/192 (0%) | |||||
| Hyponatraemia | 0/146 (0%) | 1/182 (0.5%) | 0/204 (0%) | 0/194 (0%) | 0/192 (0%) | |||||
| Hypovolaemia | 0/146 (0%) | 1/182 (0.5%) | 0/204 (0%) | 0/194 (0%) | 0/192 (0%) | |||||
| Dehydration | 0/146 (0%) | 0/182 (0%) | 0/204 (0%) | 1/194 (0.5%) | 0/192 (0%) | |||||
| Musculoskeletal and connective tissue disorders | ||||||||||
| Back pain | 0/146 (0%) | 1/182 (0.5%) | 0/204 (0%) | 0/194 (0%) | 1/192 (0.5%) | |||||
| Musculoskeletal pain | 0/146 (0%) | 0/182 (0%) | 0/204 (0%) | 1/194 (0.5%) | 0/192 (0%) | |||||
| Osteoarthritis | 0/146 (0%) | 0/182 (0%) | 0/204 (0%) | 0/194 (0%) | 1/192 (0.5%) | |||||
| Lumbar spinal stenosis | 0/146 (0%) | 0/182 (0%) | 0/204 (0%) | 0/194 (0%) | 1/192 (0.5%) | |||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||
| Bladder transitional cell carcinoma | 0/146 (0%) | 0/182 (0%) | 0/204 (0%) | 0/194 (0%) | 1/192 (0.5%) | |||||
| Lung adenocarcinoma | 0/146 (0%) | 0/182 (0%) | 0/204 (0%) | 1/194 (0.5%) | 0/192 (0%) | |||||
| Metastatic renal cell carcinoma | 0/146 (0%) | 0/182 (0%) | 0/204 (0%) | 0/194 (0%) | 1/192 (0.5%) | |||||
| Transitional cell carcinoma | 0/146 (0%) | 1/182 (0.5%) | 0/204 (0%) | 0/194 (0%) | 0/192 (0%) | |||||
| Nervous system disorders | ||||||||||
| Cerebrovascular accident | 0/146 (0%) | 0/182 (0%) | 0/204 (0%) | 2/194 (1%) | 0/192 (0%) | |||||
| Carotid artery stenosis | 0/146 (0%) | 0/182 (0%) | 1/204 (0.5%) | 0/194 (0%) | 0/192 (0%) | |||||
| Cervical myelopathy | 0/146 (0%) | 0/182 (0%) | 1/204 (0.5%) | 0/194 (0%) | 0/192 (0%) | |||||
| Ataxia | 0/146 (0%) | 1/182 (0.5%) | 0/204 (0%) | 0/194 (0%) | 0/192 (0%) | |||||
| Syncope | 1/146 (0.7%) | 0/182 (0%) | 2/204 (1%) | 0/194 (0%) | 1/192 (0.5%) | |||||
| Convulsion | 0/146 (0%) | 0/182 (0%) | 0/204 (0%) | 1/194 (0.5%) | 0/192 (0%) | |||||
| Psychiatric disorders | ||||||||||
| Anxiety | 0/146 (0%) | 0/182 (0%) | 0/204 (0%) | 0/194 (0%) | 1/192 (0.5%) | |||||
| Affective disorder | 0/146 (0%) | 0/182 (0%) | 0/204 (0%) | 0/194 (0%) | 1/192 (0.5%) | |||||
| Renal and urinary disorders | ||||||||||
| Renal failure acute | 0/146 (0%) | 0/182 (0%) | 0/204 (0%) | 1/194 (0.5%) | 0/192 (0%) | |||||
| Nephrolithiasis | 0/146 (0%) | 0/182 (0%) | 1/204 (0.5%) | 0/194 (0%) | 0/192 (0%) | |||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||
| Acute respiratory failure | 0/146 (0%) | 0/182 (0%) | 2/204 (1%) | 1/194 (0.5%) | 1/192 (0.5%) | |||||
| Pulmonary mass | 0/146 (0%) | 2/182 (1.1%) | 0/204 (0%) | 0/194 (0%) | 0/192 (0%) | |||||
| Vascular disorders | ||||||||||
| Deep vein thrombosis | 1/146 (0.7%) | 0/182 (0%) | 0/204 (0%) | 0/194 (0%) | 0/192 (0%) | |||||
| Peripheral vascular disorder | 0/146 (0%) | 1/182 (0.5%) | 0/204 (0%) | 0/194 (0%) | 0/192 (0%) | |||||
| Hypertension | 1/146 (0.7%) | 0/182 (0%) | 0/204 (0%) | 0/194 (0%) | 1/192 (0.5%) | |||||
| Hypotension | 0/146 (0%) | 0/182 (0%) | 2/204 (1%) | 0/194 (0%) | 1/192 (0.5%) | |||||
Other (Not Including Serious) Adverse Events |
||||||||||
| Placebo | Aclidinium/Formoterol 400/12 μg | Aclidinium/Formoterol 400/6 μg | Aclidinium 400 μg | Formoterol 12 μg | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 37/146 (25.3%) | 59/182 (32.4%) | 64/204 (31.4%) | 67/194 (34.5%) | 62/192 (32.3%) | |||||
| Infections and infestations | ||||||||||
| Nasopharyngitis | 7/146 (4.8%) | 14/182 (7.7%) | 14/204 (6.9%) | 18/194 (9.3%) | 13/192 (6.8%) | |||||
| Urinary tract infection | 8/146 (5.5%) | 15/182 (8.2%) | 13/204 (6.4%) | 8/194 (4.1%) | 11/192 (5.7%) | |||||
| Upper respiratory tract infection | 8/146 (5.5%) | 5/182 (2.7%) | 8/204 (3.9%) | 9/194 (4.6%) | 8/192 (4.2%) | |||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||
| Cough | 3/146 (2.1%) | 5/182 (2.7%) | 6/204 (2.9%) | 12/194 (6.2%) | 5/192 (2.6%) | |||||
| Chronic obstructive pulmonary disease | 23/146 (15.8%) | 37/182 (20.3%) | 45/204 (22.1%) | 44/194 (22.7%) | 46/192 (24%) | |||||
Limitations/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
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Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Publication of the results by the Principal Investigator (PI) will be subject to mutual agreement between the PI and the sponsor
Results Point of Contact
| Name/Title | Study Director |
|---|---|
| Organization | AstraZeneca |
| Phone | |
| ClinicalTrialTransparency@astrazeneca.com |
Responsible Party:
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01572792
Other Study ID Numbers:
- LAC-MD-36
First Posted:
Apr 6, 2012
Last Update Posted:
Apr 21, 2017
Last Verified:
Feb 1, 2017