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Study for subjects 40 to 65 years-old with a diagnosis of moderate to severe COPD. Aclidinium bromide 400 mcg 2x a day will be given as an active comparator.
This is a randomized, six-way crossover study to determine the efficacy and dose-response profile of SUN101. The study population will consist of subjects 40 to 65 years-old (inclusive), with a diagnosis of moderate to severe COPD. Aclidinium bromide 400 mcg bid will be given as an active comparator. The study will be double-blind for SUN-101 and placebo and will be open-label for aclidinium.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo | Placebo Comparator | Placebo bid |
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| SUN-101 3 mcg | Experimental | SUN-101 3 mcg bid |
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| SUN-101 6.25 mcg | Experimental | SUN-101 6.25 mcg bid |
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| SUN-101 12.5 mcg | Experimental | SUN-101 12.5 mcg bid |
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| SUN-101 50 mcg | Experimental | SUN-101 50 mcg bid |
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| Aclidinium 400 mcg | Active Comparator | Aclidinium 400 mcg bid |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Placebo | Drug | Placebo |
| |
| SUN101 3 mcg |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Trough FEV1 at Treatment Visit Day 7 Compared to Placebo. | Spirometry was performed according to internationally accepted standards. Trough FEV1 was defined as the average of the 2 spirometry values collected at 23 hours 15 minutes, and 23 hours 45 minutes post-morning dose on Day 7 of each Treatment Period. The FEV1 values within 6 hours after the use of rescue medication were considered as missing. Baseline was calculated as the mean of the FEV1 values at 45 minutes and 15 minutes prior to the morning dose at Day 1 of each Treatment Period | Baseline and Day 7 |
| Measure | Description | Time Frame |
|---|---|---|
| Standardized Change From Baseline in FEV1 AUC(0-12hours) | The standardized FEV1 AUC(0-12) on Day 7 was calculated using the trapezoidal rule from the changes in FEV1 from the baseline value (the mean of the two FEV1 values at 45 minutes and 15 minutes prior to morning dose at Day 1 of the respective Treatment Periods) and dividing by the actual length of the time interval). | Day 7 |
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Inclusion Criteria:
Male or female patients 40 to 65 years-old, inclusive.
A clinical diagnosis of moderate to severe COPD according to the GOLD 2011 guidelines.
Current smokers or ex-smokers with at least 10 pack year smoking history (eg, at least 1 pack/day for 10 years, or equivalent).
Post bronchodilator (following inhalation of ipratropium bromide) FEV1 ≥ 40% and ≤ 70% of predicted normal during Screening.
Post bronchodilator (following inhalation of ipratropium bromide) FEV1/FVC ratio ≤ 0.70 during Screening.
Post bronchodilator (following inhalation of ipratropium bromide) improvement in FEV1 ≥ 12% and ≥ 100 mL during Screening.
Ability to perform reproducible spirometry according to the American Thoracic Society (ATS) and European Respiratory Society (ERS) guidelines (2005).
Female of child bearing potential (only) must have a negative serum pregnancy test at Screening and be neither breastfeeding nor intending to become pregnant during study participation. Females of childbearing potential must be instructed to and agree to avoid pregnancy during the study. Female subjects of child bearing potential must use an adequate method of birth control from Screening until 30 days after receiving study drug and use contraception in addition to their partners using a barrier method. Acceptable forms of contraception are as follows:
Willing and able to remain at the study site for at least 24 hours at Day 7 of each Treatment Period.
Willing and able to attend all study visits and adhere to all study assessments/procedures.
Willing and able to provide written informed consent
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| SUN101 Medical Director, MD | Sumitomo Pharma America, Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Clinical Research of West Florida, Inc. | Clearwater | Florida | 33765 | United States | ||
| American Health Research, Inc. |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29202767 | Result | Donohue JF, Goodin T, Tosiello R, Wheeler A. Dose selection for glycopyrrolate/eFlow(R) phase III clinical studies: results from GOLDEN (Glycopyrrolate for Obstructive Lung Disease via Electronic Nebulizer) phase II dose-finding studies. Respir Res. 2017 Dec 4;18(1):202. doi: 10.1186/s12931-017-0681-z. |
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Eligible subjects will be randomized to one of 12 treatment sequences. There will be a minimum of a 7-day washout period between each treatment visit. At each visit, subjects will receive one dose of study medication according to the sequence assigned.
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| ID | Title | Description |
|---|---|---|
| FG000 | Treatment Group 1 | Participants received SUN-101 50mcg; Aclidinium 400mcg; Placebo; SUN-101 6,25mcg; SUN-101 3mcg; SUN-101 12.5mcg |
| FG001 | Treatment Group 2 | Participants received Placebo; SUN-101 50mcg; SUN-101 3mcg Aclidinium 400mcg; SUN-101 12.5 mcg; SUN-101 6mcg |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Treatment Period 1 |
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| Drug |
SUN-101 3 mcg bid |
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| SUN-101 6.25 mcg | Drug | SUN-101 6.25 mcg bid |
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| SUN-101 12.5 mcg | Drug | SUN-101 12.5 mcg bid |
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| SUN-101 50 mcg | Drug | SUN-101 50 mcg bid |
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| Aclidinium | Drug | Aclidinium 400 mcg bid |
|
| Number of Subjects With Treatment-emergent Adverse Events (Overall and by Treatment) | A treatment emergent adverse event (TEAE) is any TEAE that occurred on or after the first dose of study medication, any SAE with a missing start date and a stop date on or after the first dose of study medication, or any TEAE with both a missing start and stop date. | Over 7 days |
| Percentage of Subjects With Treatment-emergent Adverse Events (Overall and by Treatment) | A treatment emergent adverse event (TEAE) is any TEAE that occurred on or after the first dose of study medication, any SAE with a missing start date and a stop date on or after the first dose of study medication, or any TEAE with both a missing start and stop date. | Over 7 days |
| Charlotte |
| North Carolina |
| 28207 |
| United States |
| North Carolina Clinical Research | Raleigh | North Carolina | 27607 | United States |
| Clinical Research Institute of Southern Oregon, PC | Medford | Oregon | 97504 | United States |
| Palmetto Medical Research Associates, LLC | Easley | South Carolina | 29640 | United States |
| Greenville Pharmaceutical Research, Inc. | Greenville | South Carolina | 29615 | United States |
| Upstate Pharmaceutical Research | Greenville | South Carolina | 29615 | United States |
| S. Carolina | Spartanburg | South Carolina | 29303 | United States |
| Spartanburg Medical Research | Spartanburg | South Carolina | 29303 | United States |
| CU Pharmaceutical Research | Union | South Carolina | 29379 | United States |
| FG002 | Treatment Group 3 | Participants received SUN-101 3mcg Placebo; SUN-101 12.5 mcg; SUN-101 50mcg; SUN-101 6.25mcg Aclidinium 400mcg; |
| FG003 | Treatment Group 4 | Participants received SUN-101 12.5 mcg; SUN-101 3mcg Placebo; SUN-101 50mcg; Aclidinium 400mcg; SUN-101 6.25mcg |
| FG004 | Treatment Group 5 | Participants received SUN-101 6.25mcg SUN-101 12.5 mcg; Aclidinium 400mcg; SUN-101 3mcg SUN-101 50mcg Placebo; Aclidinium 400mcg; SUN-101 6.25mcg |
| FG005 | Treatment Group 6 | Participants received Aclidinium 400mcg; SUN-101 6.25mcg SUN-101 50mcg SUN-101 12.5 mcg; Placebo; SUN-101 3mcg Placebo; |
| FG006 | Treatment Group 7 | Participants received SUN-101 3mcg SUN-101 50mcg Aclidinium 400mcg; Placebo; SUN-101 6.25mcg SUN-101 12.5 mcg; SUN-101 3mcg |
| FG007 | Treatment Group 8 | Participants received Aclidinium 400mcg; SUN-101 3mcg SUN-101 6.25mcg SUN-101 50mcg SUN-101 12.5 mcg; Placebo; |
| FG008 | Treatment Group 9 | Participants received SUN-101 6.25mcg Aclidinium 400mcg; SUN-101 12.5 mcg SUN-101 3mcg Placebo; SUN-101 50mcg |
| FG009 | Treatment Group 10 | Participants received SUN-101 12.5 mcg SUN-101 6.25mcg Placebo; Aclidinium 400mcg; SUN-101 50 mcg SUN-101 3mcg |
| FG010 | Treatment Group 11 | Participants received Placebo; SUN-101 12.5 mcg SUN-101 50 mcg SUN-101 6.25mcg Aclidinium 400mcg; SUN-101 3mcg |
| FG011 | Treatment Group 12 | Participants received SUN-101 50 mcg Placebo; SUN-101 3mcg SUN-101 6.25mcg Aclidinium 400mcg; SUN-101 12.5 mcg |
| COMPLETED |
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| NOT COMPLETED |
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| Washout Period 1 |
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| Treatment Period 2 |
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| Washout Period 2 |
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| Treatment Period 3 |
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| Washout Period 3 |
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| Treatment Period 4 |
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| Washout Period 4 |
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| Treatment Period 5 |
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| Washout Period 5 |
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| Treatment Period 6 |
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| ID | Title | Description |
|---|---|---|
| BG000 | Total | Total of all participants |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
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| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Count of Participants | Participants | No |
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| 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 Trough FEV1 at Treatment Visit Day 7 Compared to Placebo. | Spirometry was performed according to internationally accepted standards. Trough FEV1 was defined as the average of the 2 spirometry values collected at 23 hours 15 minutes, and 23 hours 45 minutes post-morning dose on Day 7 of each Treatment Period. The FEV1 values within 6 hours after the use of rescue medication were considered as missing. Baseline was calculated as the mean of the FEV1 values at 45 minutes and 15 minutes prior to the morning dose at Day 1 of each Treatment Period | Efficacy Population: all subjects who were randomized to treatment, received at least one dose of study medication, and had at least one trough FEV1 evaluation and the corresponding baseline FEV1 for at least one treatment period. | Posted | Least Squares Mean | Standard Error | liters | Baseline and Day 7 |
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| Secondary | Standardized Change From Baseline in FEV1 AUC(0-12hours) | The standardized FEV1 AUC(0-12) on Day 7 was calculated using the trapezoidal rule from the changes in FEV1 from the baseline value (the mean of the two FEV1 values at 45 minutes and 15 minutes prior to morning dose at Day 1 of the respective Treatment Periods) and dividing by the actual length of the time interval). | Efficacy Population: all subjects who were randomized to treatment, received at least one dose of study medication, and had at least one trough FEV1 evaluation and the corresponding baseline FEV1 for at least one treatment period. | Posted | Least Squares Mean | Standard Error | Liters | Day 7 |
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| Secondary | Number of Subjects With Treatment-emergent Adverse Events (Overall and by Treatment) | A treatment emergent adverse event (TEAE) is any TEAE that occurred on or after the first dose of study medication, any SAE with a missing start date and a stop date on or after the first dose of study medication, or any TEAE with both a missing start and stop date. | Safety population was defined as all subjects who were randomized to treatment and received at least one dose of study medication. | Posted | Number | participants | Over 7 days |
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| Secondary | Percentage of Subjects With Treatment-emergent Adverse Events (Overall and by Treatment) | A treatment emergent adverse event (TEAE) is any TEAE that occurred on or after the first dose of study medication, any SAE with a missing start date and a stop date on or after the first dose of study medication, or any TEAE with both a missing start and stop date. | Safety population was defined as all subjects who were randomized to treatment and received at least one dose of study medication. | Posted | Number | percentage of participants | Over 7 days |
|
Over 7 days
A treatment emergent serious adverse event (TESAE) is any SAE that occurred on or after the first dose of study medication, any SAE with a missing start date and a stop date on or after the first dose of study medication, or any SAE with both a missing start and stop date.
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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 | Placebo | Placebo bid Placebo: Placebo | 1 | 92 | 2 | 92 | ||
| EG001 | SUN-101 3 mcg | SUN-101 3 mcg bid SUN101 3 mcg: SUN-101 3 mcg bid | 0 | 91 | 6 | 91 | ||
| EG002 | SUN-101 6.25 mcg | SUN-101 6.25 mcg bid SUN-101 6.25 mcg: SUN-101 6.25 mcg bid | 2 | 92 | 4 | 92 | ||
| EG003 | SUN-101 12.5 mcg | SUN-101 12.5 mcg bid SUN-101 12.5 mcg: SUN-101 12.5 mcg bid | 1 | 90 | 6 | 90 | ||
| EG004 | SUN-101 50 mcg | SUN-101 50 mcg bid SUN-101 50 mcg: SUN-101 50 mcg bid | 0 | 92 | 5 | 92 | ||
| EG005 | Aclidinium 400 mcg | Aclidinium 400 mcg bid Aclidinium: Aclidinium 400 mcg bid | 3 | 94 | 10 | 94 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| acute myocardial infarction | Cardiac disorders | MedDRA 15.1 | Systematic Assessment |
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| atrial fibrillation | Cardiac disorders | MedDRA 15.1 | Systematic Assessment |
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| cardia failure acute | Cardiac disorders | MedDRA 15.1 | Systematic Assessment |
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| chest pain | General disorders | MedDRA 15.1 | Systematic Assessment |
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| bronchitis | Infections and infestations | MedDRA 15.1 | Systematic Assessment |
| |
| metapneumovirus infection | Infections and infestations | MedDRA 15.1 | Systematic Assessment |
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| Toxicity to various agents | Injury, poisoning and procedural complications | MedDRA 15.1 | Systematic Assessment |
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| chronic obstructive pulmonary disease | Respiratory, thoracic and mediastinal disorders | MedDRA 15.1 | Systematic Assessment |
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| pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA 15.1 | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Dysgeusia | Nervous system disorders | MedDRA 15.1 | Systematic Assessment |
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| cough | Respiratory, thoracic and mediastinal disorders | MedDRA 15.1 | Systematic Assessment |
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In the event the Study is part of a multi-center study, the first publication of the results of the Study shall be made in conjunction with the results of other participating study sites as a multi-center publication; provided however, if a multi-center publication is not forthcoming within twenty-four (24) months following completion of the Study at all sites, Institution and Investigator shall be free to publish.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Respiratory Medical Director | Sunovion Pharmaceuticals Inc. | 1-866-503-6351 |
| ID | Term |
|---|---|
| D029424 | Pulmonary Disease, Chronic Obstructive |
| 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 |
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| ID | Term |
|---|---|
| C542859 | aclidinium bromide |
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| Withdrawal by Subject |
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| Withdrawal by Subject |
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| Unknown or Not Reported |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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| Superiority |
A sample size of 66 subjects (rounding to 72 for using Williams squares and 96 with dropouts) provides ~90% power to detect a 100 mL treatment difference in mean change trough FEV1 between SUN-101 and placebo at a Bonferroni-adjusted significance level of 0.0125 using a 2-tailed paired t-test and assuming a within-subject standard deviation for change in trough FEV1 of 176 and a within-subject correlation of 0.3. |
| An mixed effects model was used with mean change from baseline in trough FEV1 as the response, with factors for treatment, period, sequence, baseline FEV1 as a covariate and a random effect for subject nested within sequence. The Kenward and Roger correction to the degrees of freedom was used. An unstructured covariance model was used to model intrasubject correlation. | LS Mean (SE) | 0.0014 | P-values were adjusted using Dunnett's method for comparing the multiple treatments to placebo. The comparison of aclidinium to placebo was performed at the 0.05 significance level to establish assay sensitivity. | LS Mean (SE) | 0.0822 | Standard Error of the Mean | 0.0225 | 2-Sided | 95 | 0.0380 | 0.1264 | Superiority | A sample size of 66 subjects (rounding to 72 for using Williams squares and 96 with dropouts) provides ~90% power to detect a 100 mL treatment difference in mean change trough FEV1 between SUN-101 and placebo at a Bonferroni-adjusted significance level of 0.0125 using a 2-tailed paired t-test and assuming a within-subject standard deviation for change in trough FEV1 of 176 and a within-subject correlation of 0.3. |
| An mixed effects model was used with mean change from baseline in trough FEV1 as the response, with factors for treatment, period, sequence, baseline FEV1 as a covariate and a random effect for subject nested within sequence. The Kenward and Roger correction to the degrees of freedom was used. An unstructured covariance model was used to model intrasubject correlation. | LS Mean (SE) | <0.0001 | P-values were adjusted using Dunnett's method for comparing the multiple treatments to placebo. The comparison of aclidinium to placebo was performed at the 0.05 significance level to establish assay sensitivity. | LS Mean (SE) | 0.1088 | Standard Error of the Mean | 0.0226 | 2-Sided | 95 | 0.0644 | 0.1532 | Superiority | A sample size of 66 subjects (rounding to 72 for using Williams squares and 96 with dropouts) provides ~90% power to detect a 100 mL treatment difference in mean change trough FEV1 between SUN-101 and placebo at a Bonferroni-adjusted significance level of 0.0125 using a 2-tailed paired t-test and assuming a within-subject standard deviation for change in trough FEV1 of 176 and a within-subject correlation of 0.3. |
| An mixed effects model was used with mean change from baseline in trough FEV1 as the response, with factors for treatment, period, sequence, baseline FEV1 as a covariate and a random effect for subject nested within sequence. The Kenward and Roger correction to the degrees of freedom was used. An unstructured covariance model was used to model intrasubject correlation | LS Mean (SE) | <0.0001 | P-values were adjusted using Dunnett's method for comparing the multiple treatments to placebo. The comparison of aclidinium to placebo was performed at the 0.05 significance level to establish assay sensitivity. | LS Mean (SE) | 0.1375 | Standard Error of the Mean | 0.0226 | 2-Sided | 95 | 0.0931 | 0.1818 | Superiority | A sample size of 66 subjects (rounding to 72 for using Williams squares and 96 with dropouts) provides ~90% power to detect a 100 mL treatment difference in mean change trough FEV1 between SUN-101 and placebo at a Bonferroni-adjusted significance level of 0.0125 using a 2-tailed paired t-test and assuming a within-subject standard deviation for change in trough FEV1 of 176 and a within-subject correlation of 0.3. |
| An mixed effects model was used with mean change from baseline in trough FEV1 as the response, with factors for treatment, period, sequence, baseline FEV1 as a covariate and a random effect for subject nested within sequence. The Kenward and Roger correction to the degrees of freedom was used. An unstructured covariance model was used to model intrasubject correlation. | LS Mean (SE) | <0.0001 | P-values were adjusted using Dunnett's method for comparing the multiple treatments to placebo. The comparison of aclidinium to placebo was performed at the 0.05 significance level to establish assay sensitivity. | LS Mean (SE) | 0.1567 | Standard Error of the Mean | 0.0226 | 2-Sided | 95 | 0.1121 | 0.2012 | Superiority | A sample size of 66 subjects (rounding to 72 for using Williams squares and 96 with dropouts) provides ~90% power to detect a 100 mL treatment difference in mean change trough FEV1 between SUN-101 and placebo at a Bonferroni-adjusted significance level of 0.0125 using a 2-tailed paired t-test and assuming a within-subject standard deviation for change in trough FEV1 of 176 and a within-subject correlation of 0.3. |
| OG004 | SUN-101 50 mcg | SUN-101 50 mcg bid SUN-101 50 mcg: SUN-101 50 mcg bid |
| OG005 | Aclidinium 400 mcg | Aclidinium 400 mcg bid Aclidinium: Aclidinium 400 mcg bid |
|
|
|
| OG004 |
| SUN-101 50 mcg |
SUN-101 50 mcg bid SUN-101 50 mcg: SUN-101 50 mcg bid |
| OG005 | Aclidinium 400 mcg | Aclidinium 400 mcg bid Aclidinium: Aclidinium 400 mcg bid |
| OG006 | TOTAL | Total number of study participants |
|
|
| OG004 |
| SUN-101 50 mcg |
SUN-101 50 mcg bid SUN-101 50 mcg: SUN-101 50 mcg bid |
| OG005 | Aclidinium 400 mcg | Aclidinium 400 mcg bid Aclidinium: Aclidinium 400 mcg bid |
| OG006 | TOTAL | Total number of study participants |
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