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The purpose of this study is to evaluate the efficacy of this multicenter, randomized, double-blind, placebo-controlled, 4-period, incomplete-block crossover, dose-ranging study comparing 2 fixed dose combinations (FDCs) of aclidinium bromide with formoterol fumarate or with placebo, aclidinium bromide and formoterol fumarate, all administered twice a day (BID) in patients with stable, moderate to severe chronic obstructive pulmonary disease (COPD) beginning with a 2-week run-in period and with a 7-10 day washout each between treatment period.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Aclidinium 400 μg / Formoterol 12 μg | Experimental | Aclidinium bromide 400 μg / formoterol fumarate 12 μg fixed dose combination administered twice-daily (BID) |
|
| Aclidinium 400 μg / formoterol 6 μg | Experimental | Aclidinium bromide 400 μg / formoterol fumarate 6 μg fixed dose combination administered twice-daily (BID) |
|
| Aclidinium 400 μg | Experimental | Aclidinium bromide 400 μg administered twice-daily (BID) |
|
| Formoterol 12 μg | Active Comparator | Formoterol fumarate 12 μg twice-daily |
|
| Placebo | Placebo Comparator | Placebo twice-daily |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Aclidinium 400 μg / Formoterol 12 μg | Drug | Aclidinium bromide 400 μg / formoterol fumarate 12 μg fixed dose combination administered twice-daily (BID) for a 14 day period within four different treatment periods. |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Normalized Forced Expiratory Volume in One Second (FEV1) Area Under the Curve Over 12 Hours (AUC0-12) | 0 to 12 hours post-dose on Day 14 |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Morning Pre-dose (Trough) Forced Expiratory Volume in One Second (FEV1) | Day 14 | |
| Change From Baseline in Morning Peak Forced Expiratory Volume in One Second (FEV1) | Day 14 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Esther Garcia, MD | AstraZeneca | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Forest Investigative Site 0909 | Glendale | Arizona | 85306 | United States | ||
| Forest Investigative Site 2050 |
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| Label | URL |
|---|---|
| lac-md-27-synopsis | View source |
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The study was conducted in a total of 20 study centers in the United States. The first patient was screened in December 2009 and the last patient visit was in August 2010.
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| ID | Title | Description |
|---|---|---|
| FG000 | Sequence 1 | Aclidiunium/Formoterol 400/6 - Aclidiunium/Formoterol 400/12 - Aclidinium - Formoterol |
| FG001 | Sequence 2 | Aclidinium/Formoterol 400/12 - Aclidinium - Formoterol - Placebo |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Period 1 |
|
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| Aclidinium 400 μg / Formoterol 6 μg | Drug | Aclidinium bromide 400 μg / formoterol fumarate 6 μg fixed dose combination administered twice-daily (BID) for a 14 day period within four different treatment periods. |
|
| Aclidinium 400 μg | Drug | Aclidinium bromide 400 μg administered twice-daily (BID) for a 14 day period within four different treatment periods. |
|
| Formoterol 12 μg | Drug | Formoterol fumarate 12 μg twice-daily for a 14 day period within four different treatment periods. |
|
| Placebo | Drug | Placebo twice-daily delivered by inhalation for a 14 day period within four different treatment periods. |
|
| Pheonix |
| Arizona |
| 85006 |
| United States |
| Forest Investigative Site 2029 | Rancho Mirage | California | 92270 | United States |
| Forest Investigative Site 1084 | Stockton | California | 95207 | United States |
| Forest Investigative Site 2045 | Wheat Ridge | Colorado | 80033 | United States |
| Forest Investigative Site 1152 | Clearwater | Florida | 33765 | United States |
| Forest Investigative Site 2053 | Tampa | Florida | 33603 | United States |
| Forest Investigative Site 2047 | Tampa | Florida | 33613 | United States |
| Forest Investigative Site 1431 | North Dartmouth | Massachusetts | 02747 | United States |
| Forest Investigative Site 2084 | Summit | New Jersey | 07901 | United States |
| Forest Investigative Site 1119 | Elmira | New York | 14901 | United States |
| Forest Investigative Site 2035 | Elizabeth City | North Carolina | 27909 | United States |
| Forest Investigative Site 1153 | Raleigh | North Carolina | 27607 | United States |
| Forest Investigative Site 2028 | Cincinnati | Ohio | 45242 | United States |
| Forest Investigative Site 2043 | Medford | Oregon | 97504 | United States |
| Forest Investigative Site 1106 | Portland | Oregon | 97213 | United States |
| Forest Investigative Site 1089 | East Providence | Rhode Island | 02914 | United States |
| Forest Investigative Site 1121 | Spartanburg | South Carolina | 29303 | United States |
| Forest Investigative Site 1498 | San Antonio | Texas | 78215 | United States |
| Forest Investigative Site 1129 | Waco | Texas | 76712 | United States |
| FG002 | Sequence 3 | Aclidinium - Formoterol - Placebo - Aclidinium/Formoterol 400/6 |
| FG003 | Sequence 4 | Formoterol - Placebo - Aclidinium/Formoterol 400/6 - Aclidinium/Formoterol 400/12 |
| FG004 | Sequence 5 | Placebo - Aclidinium/Formoterol 400/6 - Aclidinium/Formoterol 400/12 - Aclidinium |
| FG005 | Sequence 6 | Aclidinium/Formoterol 400/6 - Aclidinium - Placebo - Aclidinium/Formoterol 400/12 |
| FG006 | Sequence 7 | Aclidinium/Formoterol 400/12 - Formoterol - Aclidinium/Formoterol 400/6 - Aclidinium |
| FG007 | Sequence 8 | Aclidinium - Placebo - Aclidinium/Formoterol 400/12 - Formoterol |
| FG008 | Sequence 9 | Formoterol - Aclidinium/Formoterol 400/6 - Aclidinium - Placebo |
| FG009 | Sequence 10 | Placebo - Aclidinium/Formoterol 400/12 - Formoterol - Aclidinium/Formoterol 400/6 |
| FG010 | Sequence 11 | Aclidinium/Formoterol 400/6 - Formoterol - Aclidinium/Formoterol 400/12 - Placebo |
| FG011 | Sequence 12 | Aclidinium/Formoterol 400/12 - Placebo - Aclidinium - Aclidinium/Formoterol 400/6 |
| FG012 | Sequence 13 | Aclidinium - Aclidinium/Formoterol 400/6 - Formoterol - Aclidinium/Formoterol 400/12 |
| FG013 | Sequence 14 | Formoterol - Aclidinium/Formoterol 400/12 - Placebo - Aclidinium |
| FG014 | Sequence 15 | Placebo - Aclidinium - Aclidinium/Formoterol 400/6 - Formoterol |
| FG015 | Sequence 16 | Aclidinium/Formoterol 400/6 - Placebo - Formoterol - Aclidinium |
| FG016 | Sequence 17 | Aclidinium/Formoterol 400/12 - Aclidinium/Formoterol 400/6 - Placebo - Formoterol |
| FG017 | Sequence 18 | Aclidinium - Aclidinium/Formoterol 400/12 - Aclidinium/Formoterol 400/6 - Placebo |
| FG018 | Sequence 19 | Formoterol - Aclidinium - Aclidinium/Formoterol 400/12 - Aclidinium/Formoterol 400/6 |
| FG019 | Sequence 20 | Placebo - Formoterol - Aclidinium - Aclidinium/Formoterol 400/12 |
| COMPLETED |
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| NOT COMPLETED |
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| Period 2 |
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| Period 3 |
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| Period 4 |
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| ID | Title | Description |
|---|---|---|
| BG000 | Overall Population | Safety population defined as all randomized patients who took at least one dose of double-blind investigational product |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | Years |
| |||||||||||||||||
| Gender | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change From Baseline in Normalized Forced Expiratory Volume in One Second (FEV1) Area Under the Curve Over 12 Hours (AUC0-12) | ITT Population defined as randomized patients who took at least one dose of double-blind investigational product and who had at least 1 baseline and 1 post-baseline assessment of FEV1 | Posted | Least Squares Mean | Standard Error | Liters | 0 to 12 hours post-dose on Day 14 |
|
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| Secondary | Change From Baseline in Morning Pre-dose (Trough) Forced Expiratory Volume in One Second (FEV1) | ITT Population defined as randomized patients who took at least one dose of double-blind investigational product and who had at least 1 baseline and 1 post-baseline assessment of FEV1 | Posted | Least Squares Mean | Standard Error | Liters | Day 14 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Change From Baseline in Morning Peak Forced Expiratory Volume in One Second (FEV1) | ITT Population defined as randomized patients who took at least one dose of double-blind investigational product and who had at least 1 baseline and 1 post-baseline assessment of FEV1 | Posted | Least Squares Mean | Standard Error | Liters | Day 14 |
|
Up to 30 days after the last dose of investigational product, for up to 24 weeks
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Aclidinium 400 μg / Formoterol 12 μg | Aclidinium bromide 400 μg / formoterol fumarate 12 μg fixed dose combination administered twice-daily (BID) | 2 | 87 | 0 | 87 | ||
| EG001 | Aclidinium 400 μg / Formoterol 6 μg | Aclidinium bromide 400 μg / formoterol fumarate 6 μg fixed dose combination administered twice-daily (BID) | 0 | 91 | 0 | 91 | ||
| EG002 | Aclidinium 400 μg | Aclidinium bromide 400 μg administered twice-daily (BID) | 1 | 94 | 0 | 94 | ||
| EG003 | Formoterol 12 μg | Formoterol fumarate 12 μg twice-daily | 1 | 92 | 0 | 92 | ||
| EG004 | Placebo | Placebo twice-daily | 0 | 92 | 0 | 92 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Chronic obstructive pulmonary disease | Respiratory, thoracic and mediastinal disorders | MedDRA v13.1 | Systematic Assessment |
| |
| Hypoglycaemia | Metabolism and nutrition disorders | MedDRA v13.1 | Systematic Assessment |
| |
| Renal failure acute | Renal and urinary disorders | MedDRA v13.1 | Systematic Assessment |
| |
| Metastatic renal cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA v13.1 | Systematic Assessment |
| |
| Coronary artery occlusion | Cardiac disorders | MedDRA v13.1 | Systematic Assessment |
|
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Publication of the results by the Investigator will be subject to mutual agreement between the investigator and sponsor.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Esther Garcia | AstraZeneca | ClinicalTrialTransparency@astrazeneca.com |
| ID | Term |
|---|---|
| D029424 | Pulmonary Disease, Chronic Obstructive |
| D029481 | Bronchitis, Chronic |
| D004646 | Emphysema |
| ID | Term |
|---|---|
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D001991 | Bronchitis |
| D012141 | Respiratory Tract Infections |
| D007239 | Infections |
| D001982 | Bronchial Diseases |
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| ID | Term |
|---|---|
| C542859 | aclidinium bromide |
| D000068759 | Formoterol Fumarate |
| ID | Term |
|---|---|
| D004983 | Ethanolamines |
| D000605 | Amino Alcohols |
| D000438 | Alcohols |
| D009930 | Organic Chemicals |
| D000588 | Amines |
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| Adverse Event |
|
| Withdrawal by Subject |
|
| Lack of Efficacy |
|
| Withdrawal by Subject |
|
| Mixed Models Analysis |
Treatment and period were fixed effects, subjects was random effect, and baseline values at each period were a covariate |
| <0.0001 |
| Least square mean difference |
| 0.202 |
| Standard Error of the Mean |
| 0.022 |
| 2-Sided |
| 95 |
| 0.158 |
| 0.245 |
| No |
| Superiority or Other |
Placebo twice-daily |
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Placebo twice-daily |
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