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The purpose of this study is to determine steady-state efficacy and dose response profile and to assess safety and pharmacokinetic profile of nebulized EP-101(SUN101) after 7-day dosing using an investigational high efficiency nebulizer (eFlow®) compared with placebo and two active comparators in patients with moderate to severe Chronic Obstructive Pulmonary Disease (COPD).
This is a phase 2, multicenter, randomized, double-blind, placebo-controlled, four-period, incomplete block design cross-over study using EP-101(SUN101) and open-label active controls (tiotropium bromide and ipratropium bromide). The study population will consist of subjects of 40-75 years of age with moderate to severe COPD. Approximately 133 subjects diagnosed with moderate to severe COPD will be enrolled in order to achieve minimum 105 subjects completing the study.
Following a run-in phase, each subject will be randomly assigned to one of 7 treatment sequences,(96 sequences when order of administration is considered), with each sequence comprised of four 7-day Treatment Periods. There will be a washout period of 7 days between each Treatment Period. Study visits will be conducted on Days 1 and 7 of each Treatment Period, with an overnight stay required in the clinic during these visits. A Final Study Visit will be conducted 7 days following the last study treatment.
During each Treatment Period, study treatments will be administered once daily (QD), except for ipratropium inhalation solution, which will be administered three times daily (TID). EP-101 (SUN101)active and placebo treatments will be administered using an investigational high-efficiency eFlow® nebulizer. Tiotropium bromide (Spiriva®) will be administered in an open-label manner via Handihaler® dry-powder inhaler (DPI). Ipratropium bromide inhalation solution will be administered in an open-label manner via general purpose nebulizer.
This study was previously posted by Elevation Pharmaceuticals, Inc. On September 5, 2012, Elevation was acquired by merger with Sunovion Pharmaceuticals Inc. ("Sunovion"), which resulted in Elevation becoming a direct wholly-owned subsidiary of Sunovion. In conjunction with this acquisition, the name of Elevation has been changed to Sunovion Respiratory Development Inc.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| EP-101 via nebulizer (eFlow®) 25 ug | Experimental | EP-101 via nebulizer (eFlow®) |
|
| Tiotropium bromide via (Spiriva® Handihaler®) | Active Comparator | Tiotropium bromide via (Spiriva® Handihaler®) |
|
| Ipratropium bromide Inhalation Solution | Active Comparator | Ipratropium bromide Inhalation Solution via Handihaler® DPI |
|
| Placebo EP-101 | Placebo Comparator | Placebo |
|
| EP-101 via nebulizer (eFlow®) 50 ug | Experimental | EP-101 via nebulizer (eFlow®) |
|
| EP-101 via nebulizer (eFlow®) 100 ug | Experimental |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| EP-101 via nebulizer (eFlow®) 25 ug | Drug | EP-101 (25 ug ) Dose 1 administered once daily for 7 days |
|
| Measure | Description | Time Frame |
|---|---|---|
| Mean Change in 24 Post Dose Trough Forced Expiratory Volume in 1 Second (FEV1) | Spirometry measurements were conducted in accordance with the current ATS/ERS 2005 guidelines. Trough FEV1 was defined as the mean of the spirometry values collected at 23 hours 30 minutes and 24 hours post dose for Day 1 and Day 7 within each Treatment Period. 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. Change from baseline was calculated as the trough FEV1 value minus the baseline for Day 1 and Day 7. | Day 1 and Day 7 |
| Standardized Change in FEV1 Area Under the Curve (AUC) (0-12hr , 12-24hr, 0-24hr) on Day 1 and Day 7 | Spirometry measurements were conducted in accordance with the current ATS/ERS 2005 guidelines. The standardized FEV1 AUC(0-12hr and 12-24hr) on Day 1 and Day 7 was calculated using the trapezoidal rule from the changes in FEV1 at Day 1 and Day 7, respectively, 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 1 and Day 7 |
| Measure | Description | Time Frame |
|---|---|---|
| Peak FEV1 (Maximum FEV1 During the First 4 Hours Post-dose on Day 1 and Day 7) | Spirometry measurements were conducted in accordance with the current ATS/ERS 2005 guidelines | Day 1 and Day 7 |
| Treatment Responders (Number of Subjects With Clinically Meaningful Change From Pre-dose in Trough FEV1 on Day 1 and Day 7) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Ahmet Tutuncu, M.D., Ph.D. | Chief Medical Officer / Elevation Pharmaceuticals, Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Elevation Investigational Site | Phoenix | Arizona | 85006 | United States | ||
| Elevation Investigational Site |
One randomized subject did not receive any study medication.
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| ID | Title | Description |
|---|---|---|
| FG000 | Total | total subjects which includes:EP-101 via nebulizer (eFlow®), Tiotropium bromide via (Spiriva® Handihaler®), Ipratropium bromide Inhalation Solution via Handihaler® DPI , and Placebo EP-101", |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Period 1-First Intervention (7 Days) |
|
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EP-101 via nebulizer (eFlow®)
|
| EP-101 via nebulizer (eFlow®) 200 ug | Experimental | EP-101 via nebulizer (eFlow®) |
|
| EP-101 via nebulizer (eFlow®) 50 ug | Drug | EP-101 (50 ug ) administered once daily for 7 days |
|
|
| EP-101 via nebulizer (eFlow®) 100 ug | Drug | EP-101 (100ug) administered once daily for 7 days |
|
|
| Placebo EP-101 | Drug | Placebo EP-101 administered once daily for 7 days |
|
|
| Tiotropium bromide via (Spiriva® Handihaler®) | Drug | Tiotropium 18 µg administered once daily for 7 days using Handihaler® DPI |
|
|
| Ipratropium bromide Inhalation Solution via Handihaler® DPI | Drug | Ipratropium 500 µg administered three times daily for 7 days using general purpose nebulizer |
|
|
| EP-101 via nebulizer (eFlow®) 200 ug | Drug | EP-101 (200) ug administered once daily for 7 days |
|
|
Spirometry measurements were conducted in accordance with the current ATS/ERS 2005 guidelines. Clinically meaningful is defined as when the change from baseline (mean of the two pre-dose values at Day 1) in 24 hour trough FEV1 on a SUN-101 treatment is more than 100 mL compared to the mean change in trough FEV1 from all subjects on the placebo treatment. |
| Day 1 and Day 7 |
| Number of Participants With Adverse Events, Vital Signs, and Clinically Significant Abnormal ECG Values and Laboratory Tests | AEs are defined as existing conditions which worsen or events which occur during the course of the clinical trial after treatment. Vital signs were performed during the screening period to confirm study eligibility and at the final study visit. ECGs were performed during the screening period to confirm study eligibility. Vital signs and ECG were additionally collected within 30 minutes pre-dose; and 30 minutes, and 1, 2, 4, 6, 12 hours, and 23 hours 45 minutes post-dose within each treatment period. Clinical laboratory assessments were conducted during the screening period, at each study visit during each treatment period, and at the final study visit. | Day 1 through Day 7 |
| Rescue Medication Use | Mean number of puffs of daily rescue medication | Day 1 through Day 7 |
| Treatment Responders (Percentage of Subjects With Clinically Meaningful Change From Pre-dose in Trough FEV1 on Day 1 and Day 7) | percentage of subjects with clinically meaningful change from pre-dose in trough FEV1 on Day 1 and Day 7 Spirometry measurements were conducted in accordance with the current ATS/ERS 2005 guidelines. | Day 1 and Day 7 |
| Los Angeles |
| California |
| 90048 |
| United States |
| Elevation Investigational Site | DeLand | Florida | 32720 | United States |
| Elevation Investigational SIte | Madisonville | Kentucky | 42431 | United States |
| Elevation Investigational Site | North Dartmouth | Massachusetts | 02747 | United States |
| Elevation Investigational Site | Charlotte | North Carolina | 28207 | United States |
| Elevation Investigational Site | Raleigh | North Carolina | 27607 | United States |
| Elevation Investigational Site | Medford | Oregon | 97504 | United States |
| Elevation Investigational Site | Spartanburg | South Carolina | 29303 | United States |
| Elevation Investigational Site | Tacoma | Washington | 98418 | United States |
| Elevation Investigational Site | Manchester | M21 8AD | United Kingdom |
| EP-101 Via Nebulizer |
|
| EP-101 Via Nebulizer |
|
| EP-101 Via Nebulizer |
|
| EP-101 Via Nebulizer |
|
| Ipratropium Bromide |
|
| Placebo |
|
| COMPLETED |
|
| NOT COMPLETED |
|
|
| Washout 1 |
|
|
| Period 2-Second Intervention (7 Days) |
|
|
| Washout 2 |
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|
| Period 3-Third Intervention (7 Days) |
|
| Washout 3 |
|
|
| Period 4-Fourth Intervention (7 Days) |
|
|
| Washout 4 |
|
|
modified Intent to Treat population for analysis set
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| ID | Title | Description |
|---|---|---|
| BG000 | Total Particiants | total of all participants in the study |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | |||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
| |||||||||||||||||||||||
| Age, Continuous | Mean | Standard Deviation | years |
| ||||||||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| |||||||||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| |||||||||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| |||||||||||||||||||||||
| Region of Enrollment | Count of Participants | Participants | No |
|
| 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 | Mean Change in 24 Post Dose Trough Forced Expiratory Volume in 1 Second (FEV1) | Spirometry measurements were conducted in accordance with the current ATS/ERS 2005 guidelines. Trough FEV1 was defined as the mean of the spirometry values collected at 23 hours 30 minutes and 24 hours post dose for Day 1 and Day 7 within each Treatment Period. 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. Change from baseline was calculated as the trough FEV1 value minus the baseline for Day 1 and Day 7. | All subjects who received at least one dose of study medication and who had Day 1 pre-dose and Day 7 trough FEV1 values were included in the modified intent to treat analysis set | Posted | Mean | Standard Deviation | liters | Day 1 and Day 7 |
|
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary | Standardized Change in FEV1 Area Under the Curve (AUC) (0-12hr , 12-24hr, 0-24hr) on Day 1 and Day 7 | Spirometry measurements were conducted in accordance with the current ATS/ERS 2005 guidelines. The standardized FEV1 AUC(0-12hr and 12-24hr) on Day 1 and Day 7 was calculated using the trapezoidal rule from the changes in FEV1 at Day 1 and Day 7, respectively, 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. | All subjects who received at least one dose of study medication and who had Day 1 pre-dose and Day 7 trough FEV1 values were included in the modified intent-to-treat (mITT) analysis set | Posted | Mean | Standard Deviation | liters | Day 1 and Day 7 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Peak FEV1 (Maximum FEV1 During the First 4 Hours Post-dose on Day 1 and Day 7) | Spirometry measurements were conducted in accordance with the current ATS/ERS 2005 guidelines | All subjects who received at least one dose of study medication and who had Day 1 pre-dose and Day 7 trough FEV1 values were included in the modified intent-to-treat (mITT) analysis set | Posted | Mean | Standard Deviation | liters | Day 1 and Day 7 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Treatment Responders (Number of Subjects With Clinically Meaningful Change From Pre-dose in Trough FEV1 on Day 1 and Day 7) | Spirometry measurements were conducted in accordance with the current ATS/ERS 2005 guidelines. Clinically meaningful is defined as when the change from baseline (mean of the two pre-dose values at Day 1) in 24 hour trough FEV1 on a SUN-101 treatment is more than 100 mL compared to the mean change in trough FEV1 from all subjects on the placebo treatment. | All subjects who received at least one dose of study medication and who had Day 1 pre-dose and Day 7 through FEV1 values were included in the modified intent-to-treat (mITT) analysis set | Posted | Number | number of participants | Day 1 and Day 7 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Number of Participants With Adverse Events, Vital Signs, and Clinically Significant Abnormal ECG Values and Laboratory Tests | AEs are defined as existing conditions which worsen or events which occur during the course of the clinical trial after treatment. Vital signs were performed during the screening period to confirm study eligibility and at the final study visit. ECGs were performed during the screening period to confirm study eligibility. Vital signs and ECG were additionally collected within 30 minutes pre-dose; and 30 minutes, and 1, 2, 4, 6, 12 hours, and 23 hours 45 minutes post-dose within each treatment period. Clinical laboratory assessments were conducted during the screening period, at each study visit during each treatment period, and at the final study visit. | All subjects who received at least one dose of study medication were included in the safety analysis. | Posted | Count of Participants | Participants | No | Day 1 through Day 7 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Rescue Medication Use | Mean number of puffs of daily rescue medication | All subjects who received at least one dose of study medication and who had Day 1 pre-dose and Day 7 through FEV1 values were included in the modified intent-to-treat (mITT) analysis set | Posted | Mean | Standard Deviation | average daily number of puffs | Day 1 through Day 7 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Treatment Responders (Percentage of Subjects With Clinically Meaningful Change From Pre-dose in Trough FEV1 on Day 1 and Day 7) | percentage of subjects with clinically meaningful change from pre-dose in trough FEV1 on Day 1 and Day 7 Spirometry measurements were conducted in accordance with the current ATS/ERS 2005 guidelines. | All subjects who received at least one dose of study medication and who had Day 1 pre-dose and Day 7 through FEV1 values were included in the modified intent-to-treat (mITT) analysis set | Posted | Number | percentage of participants | Day 1 and Day 7 |
|
day 1 through day 7
existing conditions which worsen or events which occur during the course of the clinical trial after treatment with randomized study drug has started
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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 | EP-101 Via Nebulizer (eFlow®) 25 mcg | EP-101 via nebulizer (eFlow®) EP-101 via nebulizer (eFlow®): EP-101 Dose 1 administered once daily for 7 days EP-101 via nebulizer (eFlow®): EP-101 administered once daily for 7 days | 0 | 74 | 8 | 74 | 0 | 74 |
| EG001 | EP-101 Via Nebulizer (eFlow®) 50 mcg | EP-101 via nebulizer (eFlow®) EP-101 via nebulizer (eFlow®): EP-101 Dose 1 administered once daily for 7 days EP-101 via nebulizer (eFlow®): EP-101 administered once daily for 7 days | 0 | 78 | 13 | 78 | 0 | 78 |
| EG002 | EP-101 Via Nebulizer (eFlow®)100 mcg | EP-101 via nebulizer (eFlow®) EP-101 via nebulizer (eFlow®): EP-101 Dose 1 administered once daily for 7 days EP-101 via nebulizer (eFlow®): EP-101 administered once daily for 7 days | 0 | 76 | 14 | 76 | 0 | 76 |
| EG003 | EP-101 Via Nebulizer (eFlow®) 200 mcg | EP-101 via nebulizer (eFlow®) EP-101 via nebulizer (eFlow®): EP-101 Dose 1 administered once daily for 7 days EP-101 via nebulizer (eFlow®): EP-101 administered once daily for 7 days | 0 | 75 | 13 | 75 | 0 | 75 |
| EG004 | Ipratropium Bromide Inhalation Solution | Ipratropium bromide Inhalation Solution via Handihaler® DPI Ipratropium bromide Inhalation Solution via Handihaler® DPI: Ipratropium 500 µg administered three times daily for 7 days using general purpose nebulizer | 0 | 75 | 5 | 75 | 0 | 75 |
| EG005 | Tiotropium Bromide Via (Spiriva® Handihaler®) | Tiotropium bromide via (Spiriva® Handihaler®) Tiotropium bromide via (Spiriva® Handihaler®): Tiotropium 18 µg administered once daily for 7 days using Handihaler® DPI | 0 | 76 | 2 | 76 | 0 | 76 |
| EG006 | Placebo | Placebo Placebo : Placebo administered once daily for 7 days | 0 | 77 | 16 | 77 | 0 | 77 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| headache | Nervous system disorders | MedDRA (14.0) | Systematic Assessment |
| |
| cough | Respiratory, thoracic and mediastinal disorders | MedDRA (14.0) | Systematic Assessment |
|
Not provided
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 |
|---|---|
| D000069447 | Tiotropium Bromide |
| D009241 | Ipratropium |
| ID | Term |
|---|---|
| D012602 | Scopolamine Derivatives |
| D014326 | Tropanes |
| D053961 | Azabicyclo Compounds |
| D001372 | Aza Compounds |
| D009930 | Organic Chemicals |
| D000470 | Alkaloids |
| D006571 | Heterocyclic Compounds |
| D019086 | Bridged Bicyclo Compounds, Heterocyclic |
| D006572 | Heterocyclic Compounds, Bridged-Ring |
| D001286 | Atropine Derivatives |
| D001533 | Belladonna Alkaloids |
| D012991 | Solanaceous Alkaloids |
Not provided
Not provided
| Unknown or Not Reported |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
|
| Trough FEV1 - day 7 |
|
|
| Superiority |
Day 7 analysis |
| An ANCOVA was used with change from baseline in trough FEV1 as the response,with factors for treatment, period, sequence, baseline as a covariate and a random effect for subject nested within sequence.A sample size of 30 subjects per comparison(133 total with dropouts)provides 90% power to detect a 0.12L difference in mean change trough FEV1 between active and placebo at an alpha of 0.05 using a 2-tailed t-test and assuming a within-subject standard deviation for change in trough FEV1 of 0.2. | ANCOVA | 0.0006 | Least Squares Mean Difference (SE) | 0.0676 | Standard Error of the Mean | 0.0184 | 2-Sided | 95 | 0.0307 | 0.1046 | Standard Error of the Mean Difference | Superiority | Day 7 analysis |
| An ANCOVA was used with change from baseline in trough FEV1 as the response, with factors for treatment, period, sequence, baseline as a covariate and a random effect for subject nested within sequence.A sample size of 30 subjects per comparison(133 total with dropouts)provides 90% power to detect a 0.12L difference in mean change trough FEV1 between active and placebo at an alpha of 0.05 using a 2-tailed t-test and assuming a within-subject standard deviation for change in trough FEV1 of 0.2. | ANCOVA | <0.0001 | Least Squares Mean Difference (SE) | 0.1021 | Standard Error of the Mean | 0.0188 | 2-Sided | 95 | 0.0644 | 0.1398 | Standard Error of the Mean Difference | Superiority | Day 7 analysis |
| An ANCOVA was used with change from baseline in trough FEV1 as the response, with factors for treatment, period, sequence, baseline as a covariate and a random effect for subject nested within sequence.A sample size of 30 subjects per comparison(133 total with dropouts)provides 90% power to detect a 0.12L difference in mean change trough FEV1 between active and placebo at an alpha of 0.05 using a 2-tailed t-test and assuming a within-subject standard deviation for change in trough FEV1 of 0.2. | ANCOVA | <0.0001 | Least Squares Mean Difference (SE) | 0.1299 | Standard Error of the Mean | 0.0190 | 2-Sided | 95 | 0.0918 | 00.1681 | Standard Error of the Mean Difference | Superiority | Day 7 analysis |
| An ANCOVA was used with change from baseline in trough FEV1 as the response, with factors for treatment, period, sequence, baseline as a covariate and a random effect for subject nested within sequence.A sample size of 30 subjects per comparison(133 total with dropouts)provides 90% power to detect a 0.12L difference in mean change trough FEV1 between active and placebo at an alpha of 0.05 using a 2-tailed t-test and assuming a within-subject standard deviation for change in trough FEV1 of 0.2. | Mantel Haenszel | 0.0200 | Least Squares Mean Difference (SE) | 0.0446 | Standard Error of the Mean | 0.0186 | 2-Sided | 95 | 0.0073 | 0.0820 | Standard Error of the Mean Difference | Superiority | Day 7 analysis |
| An ANCOVA was used with change from baseline in trough FEV1 as the response, with factors for treatment, period, sequence, baseline as a covariate and a random effect for subject nested within sequence.A sample size of 30 subjects per comparison(133 total with dropouts)provides 90% power to detect a 0.12L difference in mean change trough FEV1 between active and placebo at an alpha of 0.05 using a 2-tailed t-test and assuming a within-subject standard deviation for change in trough FEV1 of 0.2. | ANCOVA | 0.0060 | Least Squares Mean Difference (SE) | 0.0813 | Standard Error of the Mean | 0.0284 | 2-Sided | 95 | 0.0243 | 0.1382 | Standard Error of the Mean Difference | Superiority | Day 7 analysis |
| An ANCOVA was used with change from baseline in trough FEV1 as the response, with factors for treatment, period, sequence, baseline as a covariate and a random effect for subject nested within sequence.A sample size of 30 subjects per comparison(133 total with dropouts)provides 90% power to detect a 0.12L difference in mean change trough FEV1 between active and placebo at an alpha of 0.05 using a 2-tailed t-test and assuming a within-subject standard deviation for change in trough FEV1 of 0.2. | ANCOVA | 0.0402 | Least Squares Mean Difference (SE) | 0.0385 | Standard Error of the Mean | 0.0183 | 2-Sided | 95 | 0.0018 | 0.0752 | Standard Error of the Mean Difference | Superiority | Day 1 analysis |
| An ANCOVA was used with change from baseline in trough FEV1 as the response, with factors for treatment, period, sequence, baseline as a covariate and a random effect for subject nested within sequence.A sample size of 30 subjects per comparison(133 total with dropouts)provides 90% power to detect a 0.12L difference in mean change trough FEV1 between active and placebo at an alpha of 0.05 using a 2-tailed t-test and assuming a within-subject standard deviation for change in trough FEV1 of 0.2. | ANCOVA | 0.0003 | Least Squares Mean Difference (SE) | 0.0696 | Standard Error of the Mean | 0.0179 | 2-Sided | 95 | 0.0337 | 0.1055 | Standard Error of the Mean Difference | Superiority | Day 1 analysis |
| An ANCOVA was used with change from baseline in trough FEV1 as the response, with factors for treatment, period, sequence, baseline as a covariate and a random effect for subject nested within sequence.A sample size of 30 subjects per comparison(133 total with dropouts)provides 90% power to detect a 0.12L difference in mean change trough FEV1 between active and placebo at an alpha of 0.05 using a 2-tailed t-test and assuming a within-subject standard deviation for change in trough FEV1 of 0.2. | ANCOVA | 0.0074 | Least Squares Mean | 0.0501 | Standard Error of the Mean | 0.0180 | 2-Sided | 95 | 0.0140 | 0.0861 | Superiority | Day 1 analysis |
EP-101 via nebulizer (eFlow®) EP-101 via nebulizer (eFlow®): EP-101 Dose 1 administered once daily for 7 days EP-101 via nebulizer (eFlow®): EP-101 administered once daily for 7 days |
| OG003 | EP-101 Via Nebulizer (eFlow®) 200 mcg | EP-101 via nebulizer (eFlow®) EP-101 via nebulizer (eFlow®): EP-101 Dose 1 administered once daily for 7 days EP-101 via nebulizer (eFlow®): EP-101 administered once daily for 7 days |
| OG004 | Ipratropium Bromide Inhalation Solution | Ipratropium bromide Inhalation Solution via Handihaler® DPI Ipratropium bromide Inhalation Solution via Handihaler® DPI: Ipratropium 500 µg administered three times daily for 7 days using general purpose nebulizer |
| OG005 | Tiotropium Bromide Via (Spiriva® Handihaler®) | Tiotropium bromide via (Spiriva® Handihaler®) Tiotropium bromide via (Spiriva® Handihaler®): Tiotropium 18 µg administered once daily for 7 days using Handihaler® DPI |
| OG006 | Placebo | Placebo Placebo : Placebo administered once daily for 7 days |
|
|
|
| OG003 |
| EP-101 Via Nebulizer (eFlow®) 200 mcg |
EP-101 via nebulizer (eFlow®) EP-101 via nebulizer (eFlow®): EP-101 Dose 1 administered once daily for 7 days EP-101 via nebulizer (eFlow®): EP-101 administered once daily for 7 days |
| OG004 | Ipratropium Bromide Inhalation Solution | Ipratropium bromide Inhalation Solution via Handihaler® DPI Ipratropium bromide Inhalation Solution via Handihaler® DPI: Ipratropium 500 µg administered three times daily for 7 days using general purpose nebulizer |
| OG005 | Tiotropium Bromide Via (Spiriva® Handihaler®) | Tiotropium bromide via (Spiriva® Handihaler®) Tiotropium bromide via (Spiriva® Handihaler®): Tiotropium 18 µg administered once daily for 7 days using Handihaler® DPI |
| OG006 | Placebo | Placebo Placebo : Placebo administered once daily for 7 days |
|
|
EP-101 via nebulizer (eFlow®)
EP-101 via nebulizer (eFlow®): EP-101 Dose 1 administered once daily for 7 days
EP-101 via nebulizer (eFlow®): EP-101 administered once daily for 7 days
| OG003 | EP-101 Via Nebulizer (eFlow®) 200 mcg | EP-101 via nebulizer (eFlow®) EP-101 via nebulizer (eFlow®): EP-101 Dose 1 administered once daily for 7 days EP-101 via nebulizer (eFlow®): EP-101 administered once daily for 7 days |
| OG004 | Ipratropium Bromide Inhalation Solution | Ipratropium bromide Inhalation Solution via Handihaler® DPI Ipratropium bromide Inhalation Solution via Handihaler® DPI: Ipratropium 500 µg administered three times daily for 7 days using general purpose nebulizer |
| OG005 | Tiotropium Bromide Via (Spiriva® Handihaler®) | Tiotropium bromide via (Spiriva® Handihaler®) Tiotropium bromide via (Spiriva® Handihaler®): Tiotropium 18 µg administered once daily for 7 days using Handihaler® DPI |
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| OG002 | EP-101 Via Nebulizer (eFlow®)100 mcg | EP-101 via nebulizer (eFlow®) EP-101 via nebulizer (eFlow®): EP-101 Dose 1 administered once daily for 7 days EP-101 via nebulizer (eFlow®): EP-101 administered once daily for 7 days |
| OG003 | EP-101 Via Nebulizer (eFlow®) 200 mcg | EP-101 via nebulizer (eFlow®) EP-101 via nebulizer (eFlow®): EP-101 Dose 1 administered once daily for 7 days EP-101 via nebulizer (eFlow®): EP-101 administered once daily for 7 days |
| OG004 | Ipratropium Bromide Inhalation Solution | Ipratropium bromide Inhalation Solution via Handihaler® DPI Ipratropium bromide Inhalation Solution via Handihaler® DPI: Ipratropium 500 µg administered three times daily for 7 days using general purpose nebulizer |
| OG005 | Tiotropium Bromide Via (Spiriva® Handihaler®) | Tiotropium bromide via (Spiriva® Handihaler®) Tiotropium bromide via (Spiriva® Handihaler®): Tiotropium 18 µg administered once daily for 7 days using Handihaler® DPI |
| OG006 | Placebo | Placebo Placebo : Placebo administered once daily for 7 days |
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| EP-101 Via Nebulizer (eFlow®) 200 mcg |
EP-101 via nebulizer (eFlow®) EP-101 via nebulizer (eFlow®): EP-101 Dose 1 administered once daily for 7 days EP-101 via nebulizer (eFlow®): EP-101 administered once daily for 7 days |
| OG004 | Ipratropium Bromide Inhalation Solution | Ipratropium bromide Inhalation Solution via Handihaler® DPI Ipratropium bromide Inhalation Solution via Handihaler® DPI: Ipratropium 500 µg administered three times daily for 7 days using general purpose nebulizer |
| OG005 | Tiotropium Bromide Via (Spiriva® Handihaler®) | Tiotropium bromide via (Spiriva® Handihaler®) Tiotropium bromide via (Spiriva® Handihaler®): Tiotropium 18 µg administered once daily for 7 days using Handihaler® DPI |
| OG006 | Placebo | Placebo Placebo : Placebo administered once daily for 7 days |
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| OG003 | EP-101 Via Nebulizer (eFlow®) 200 mcg | EP-101 via nebulizer (eFlow®) EP-101 via nebulizer (eFlow®): EP-101 Dose 1 administered once daily for 7 days EP-101 via nebulizer (eFlow®): EP-101 administered once daily for 7 days |
| OG004 | Ipratropium Bromide Inhalation Solution | Ipratropium bromide Inhalation Solution via Handihaler® DPI Ipratropium bromide Inhalation Solution via Handihaler® DPI: Ipratropium 500 µg administered three times daily for 7 days using general purpose nebulizer |
| OG005 | Tiotropium Bromide Via (Spiriva® Handihaler®) | Tiotropium bromide via (Spiriva® Handihaler®) Tiotropium bromide via (Spiriva® Handihaler®): Tiotropium 18 µg administered once daily for 7 days using Handihaler® DPI |
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