Study to Investigate the Dose Response, Safety and Efficacy of Nebulized EP-101(SUN101) in Patients With Chronic Obstructive Pulmonary Disease (COPD): GOLDEN-1 Study
Sponsor
Sunovion Respiratory Development Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT01426009
Collaborator
(none)
140
11
7
4
12.7
3.2
Study Details
Study Description
Brief Summary
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).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
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.
Study Design
Study Type:
Interventional
Actual Enrollment
:
140 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Randomized, Double-Blind, Placebo-Controlled, Multi-Center, Seven Arm, Four-Period Cross-over, Incomplete Block Design, 7-Day Dosing Study to Assess the Dose-Response, Safety, and Efficacy of EP-101 (SUN101) in Subjects With Moderate to Severe COPD
Study Start Date
:
Aug 1, 2011
Actual Primary Completion Date
:
Dec 1, 2011
Actual Study Completion Date
:
Dec 1, 2011
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: EP-101 via nebulizer (eFlow®) 25 ug EP-101 via nebulizer (eFlow®) |
Drug: EP-101 via nebulizer (eFlow®) 25 ug
EP-101 (25 ug ) Dose 1 administered once daily for 7 days
Other Names:
|
| Active Comparator: Tiotropium bromide via (Spiriva® Handihaler®) Tiotropium bromide via (Spiriva® Handihaler®) |
Drug: Tiotropium bromide via (Spiriva® Handihaler®)
Tiotropium 18 µg administered once daily for 7 days using Handihaler® DPI
Other Names:
|
| Active Comparator: Ipratropium bromide Inhalation Solution Ipratropium bromide Inhalation Solution via Handihaler® DPI |
Drug: Ipratropium bromide Inhalation Solution via Handihaler® DPI
Ipratropium 500 µg administered three times daily for 7 days using general purpose nebulizer
Other Names:
|
| Placebo Comparator: Placebo EP-101 Placebo |
Drug: Placebo EP-101
Placebo EP-101 administered once daily for 7 days
Other Names:
|
| Experimental: EP-101 via nebulizer (eFlow®) 50 ug EP-101 via nebulizer (eFlow®) |
Drug: EP-101 via nebulizer (eFlow®) 50 ug
EP-101 (50 ug ) administered once daily for 7 days
Other Names:
|
| Experimental: EP-101 via nebulizer (eFlow®) 100 ug EP-101 via nebulizer (eFlow®) |
Drug: EP-101 via nebulizer (eFlow®) 100 ug
EP-101 (100ug) administered once daily for 7 days
Other Names:
|
| Experimental: EP-101 via nebulizer (eFlow®) 200 ug EP-101 via nebulizer (eFlow®) |
Drug: EP-101 via nebulizer (eFlow®) 200 ug
EP-101 (200) ug administered once daily for 7 days
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Mean Change in 24 Post Dose Trough Forced Expiratory Volume in 1 Second (FEV1) [Day 1 and Day 7]
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.
- Standardized Change in FEV1 Area Under the Curve (AUC) (0-12hr , 12-24hr, 0-24hr) on Day 1 and Day 7 [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.
Secondary Outcome Measures
- Peak FEV1 (Maximum FEV1 During the First 4 Hours Post-dose on Day 1 and Day 7) [Day 1 and Day 7]
Spirometry measurements were conducted in accordance with the current ATS/ERS 2005 guidelines
- Treatment Responders (Number of Subjects With Clinically Meaningful Change From Pre-dose in Trough FEV1 on Day 1 and Day 7) [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.
- Number of Participants With Adverse Events, Vital Signs, and Clinically Significant Abnormal ECG Values and Laboratory Tests [Day 1 through Day 7]
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.
- Rescue Medication Use [Day 1 through Day 7]
Mean number of puffs of daily rescue medication
- Treatment Responders (Percentage of Subjects With Clinically Meaningful Change From Pre-dose in Trough FEV1 on Day 1 and Day 7) [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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
40 Years
to 75 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
40-75 years of age
-
Clinical diagnosis of moderate to severe COPD
-
Current/ex-smokers with at least 10 pack-year smoking history
-
Post-bronchodilator FEV1 ≥ 30% and ≤ 70% predicted normal values
-
Post-bronchodilator FEV1/FVC ratio of ≤ 0.70
-
Post-bronchodilator improvement in FEV1 ≥ 12% and ≤ 30%, and a minimum of 100 mL
-
Willing and able to remain at the study site for at least 24 hours at each study visit
-
Signed written informed consent
Exclusion Criteria:
-
Current evidence or recent history of any clinically significant and unstable disease or abnormality (e.g., myocardial infarction, cardiac failure, uncontrolled hypertension, life-threatening arrhythmias, uncontrolled diabetes)
-
Primary diagnosis of asthma
-
History of malignancy within the past 5 years
-
History of COPD exacerbation within 6 weeks of Screening
-
Daily oxygen therapy > 10 hours per day
-
Systemic steroids use within 6 weeks of Screening
-
Respiratory tract infection within 6 weeks of Screening
-
History of tuberculosis, bronchiectasis
-
History of urinary retention or bladder neck obstruction type symptoms
-
History of glaucoma
-
Prolonged QTc interval (>460msec) or history of long QT syndrome
-
Recent history of alcohol or drug abuse
-
Females who are pregnant or breastfeeding, or if of child-bearing potential unwilling to practice acceptable birth control methods
-
History of hypersensitivity or intolerance to aerosol medications
-
Participation in another investigational drug study within 30 days of Screening
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Elevation Investigational Site | Phoenix | Arizona | United States | 85006 |
| 2 | Elevation Investigational Site | Los Angeles | California | United States | 90048 |
| 3 | Elevation Investigational Site | DeLand | Florida | United States | 32720 |
| 4 | Elevation Investigational SIte | Madisonville | Kentucky | United States | 42431 |
| 5 | Elevation Investigational Site | North Dartmouth | Massachusetts | United States | 02747 |
| 6 | Elevation Investigational Site | Charlotte | North Carolina | United States | 28207 |
| 7 | Elevation Investigational Site | Raleigh | North Carolina | United States | 27607 |
| 8 | Elevation Investigational Site | Medford | Oregon | United States | 97504 |
| 9 | Elevation Investigational Site | Spartanburg | South Carolina | United States | 29303 |
| 10 | Elevation Investigational Site | Tacoma | Washington | United States | 98418 |
| 11 | Elevation Investigational Site | Manchester | United Kingdom | M21 8AD |
Sponsors and Collaborators
- Sunovion Respiratory Development Inc.
Investigators
- Study Director: Ahmet Tutuncu, M.D., Ph.D., Chief Medical Officer / Elevation Pharmaceuticals, Inc.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Sunovion Respiratory Development Inc.
ClinicalTrials.gov Identifier:
NCT01426009
Other Study ID Numbers:
- EP-101-03
First Posted:
Aug 30, 2011
Last Update Posted:
May 9, 2018
Last Verified:
May 1, 2018
Keywords provided by Sunovion Respiratory Development Inc.
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | One randomized subject did not receive any study medication. |
| Arm/Group Title | Total |
|---|---|
| Arm/Group Description | 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", |
| Period Title: Period 1-First Intervention (7 Days) | |
| STARTED | 139 |
| EP-101 Via Nebulizer | 23 |
| EP-101 Via Nebulizer | 24 |
| EP-101 Via Nebulizer | 22 |
| EP-101 Via Nebulizer | 23 |
| Ipratropium Bromide | 23 |
| Placebo | 24 |
| COMPLETED | 137 |
| NOT COMPLETED | 2 |
| Period Title: Period 1-First Intervention (7 Days) | |
| STARTED | 137 |
| COMPLETED | 135 |
| NOT COMPLETED | 2 |
| Period Title: Period 1-First Intervention (7 Days) | |
| STARTED | 135 |
| EP-101 Via Nebulizer | 22 |
| EP-101 Via Nebulizer | 24 |
| EP-101 Via Nebulizer | 24 |
| EP-101 Via Nebulizer | 23 |
| Ipratropium Bromide | 21 |
| Placebo | 21 |
| COMPLETED | 130 |
| NOT COMPLETED | 5 |
| Period Title: Period 1-First Intervention (7 Days) | |
| STARTED | 130 |
| COMPLETED | 129 |
| NOT COMPLETED | 1 |
| Period Title: Period 1-First Intervention (7 Days) | |
| STARTED | 129 |
| EP-101 Via Nebulizer | 19 |
| EP-101 Via Nebulizer | 23 |
| EP-101 Via Nebulizer | 22 |
| EP-101 Via Nebulizer | 20 |
| Ipratropium Bromide | 23 |
| Placebo | 22 |
| COMPLETED | 129 |
| NOT COMPLETED | 0 |
| Period Title: Period 1-First Intervention (7 Days) | |
| STARTED | 129 |
| COMPLETED | 128 |
| NOT COMPLETED | 1 |
| Period Title: Period 1-First Intervention (7 Days) | |
| STARTED | 128 |
| EP-101 Via Nebulizer | 10 |
| EP-101 Via Nebulizer | 7 |
| EP-101 Via Nebulizer | 8 |
| EP-101 Via Nebulizer | 9 |
| Ipratropium Bromide | 8 |
| Tiotropium Bromide | 76 |
| Placebo | 10 |
| COMPLETED | 127 |
| NOT COMPLETED | 1 |
| Period Title: Period 1-First Intervention (7 Days) | |
| STARTED | 127 |
| COMPLETED | 126 |
| NOT COMPLETED | 1 |
Baseline Characteristics
| Arm/Group Title | Total Particiants |
|---|---|
| Arm/Group Description | total of all participants in the study |
| Overall Participants | 139 |
| Age (Count of Participants) | |
| <=18 years |
0
0%
|
| Between 18 and 65 years |
88
63.3%
|
| >=65 years |
51
36.7%
|
| Age (years) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [years] |
61.4
(8.11)
|
| Sex: Female, Male (Count of Participants) | |
| Female |
78
56.1%
|
| Male |
61
43.9%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |
| Hispanic or Latino |
1
0.7%
|
| Not Hispanic or Latino |
138
99.3%
|
| Unknown or Not Reported |
0
0%
|
| Race (NIH/OMB) (Count of Participants) | |
| American Indian or Alaska Native |
1
0.7%
|
| Asian |
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
| Black or African American |
4
2.9%
|
| White |
134
96.4%
|
| More than one race |
0
0%
|
| Unknown or Not Reported |
0
0%
|
| Region of Enrollment (Count of Participants) | |
| United States |
120
86.3%
|
| United Kingdom |
19
13.7%
|
Outcome Measures
| Title | Mean Change in 24 Post Dose Trough Forced Expiratory Volume in 1 Second (FEV1) |
|---|---|
| Description | 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. |
| Time Frame | Day 1 and Day 7 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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 |
| Arm/Group Title | EP-101 Via Nebulizer (eFlow®) 25 mcg | EP-101 Via Nebulizer (eFlow®) 50 mcg | EP-101 Via Nebulizer (eFlow®)100 mcg | EP-101 Via Nebulizer (eFlow®) 200 mcg | Ipratropium Bromide Inhalation Solution | Tiotropium Bromide Via (Spiriva® Handihaler®) | Placebo |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | 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 | 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 | 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 | 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 | 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 | Tiotropium bromide via (Spiriva® Handihaler®) Tiotropium bromide via (Spiriva® Handihaler®): Tiotropium 18 µg administered once daily for 7 days using Handihaler® DPI | Placebo Placebo : Placebo administered once daily for 7 days |
| Measure Participants | 72 | 75 | 75 | 75 | 72 | 76 | 77 |
| Trough FEV1 - day 1 |
0.0477
(0.16359)
|
0.1009
(0.13261)
|
0.0648
(0.14239)
|
0.0632
(0.14965)
|
0.0933
(0.18980)
|
0.0740
(0.144441)
|
0.0301
(0.14394)
|
| Trough FEV1 - day 7 |
0.0478
(0.18965)
|
0.0699
(0.16909)
|
0.0666
(0.15132)
|
0.0840
(0.13842)
|
0.0292
(0.16507)
|
0.0564
(0.16356)
|
-0.155
(0.17934)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | EP-101 Via Nebulizer (eFlow®) 25 mcg, Placebo |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority | |
| Comments | Day 7 analysis | |
| Statistical Test of Hypothesis | p-Value | 0.0003 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Squares Mean Difference (SE) |
| Estimated Value | 0.0723 | |
| Confidence Interval |
(2-Sided) 95% 0.0347 to 0.1099 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0188 |
|
| Estimation Comments | Standard Error of the Mean Difference | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | EP-101 Via Nebulizer (eFlow®) 50 mcg, Placebo |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority | |
| Comments | Day 7 analysis | |
| Statistical Test of Hypothesis | p-Value | 0.0006 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Squares Mean Difference (SE) |
| Estimated Value | 0.0676 | |
| Confidence Interval |
(2-Sided) 95% 0.0307 to 0.1046 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0184 |
|
| Estimation Comments | Standard Error of the Mean Difference | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | EP-101 Via Nebulizer (eFlow®)100 mcg, Placebo |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority | |
| Comments | Day 7 analysis | |
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Squares Mean Difference (SE) |
| Estimated Value | 0.1021 | |
| Confidence Interval |
(2-Sided) 95% 0.0644 to 0.1398 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0188 |
|
| Estimation Comments | Standard Error of the Mean Difference | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | EP-101 Via Nebulizer (eFlow®) 200 mcg, Placebo |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority | |
| Comments | Day 7 analysis | |
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Squares Mean Difference (SE) |
| Estimated Value | 0.1299 | |
| Confidence Interval |
(2-Sided) 95% 0.0918 to 00.1681 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0190 |
|
| Estimation Comments | Standard Error of the Mean Difference | |
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Ipratropium Bromide Inhalation Solution, Placebo |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority | |
| Comments | Day 7 analysis | |
| Statistical Test of Hypothesis | p-Value | 0.0200 |
| Comments | ||
| Method | Mantel Haenszel | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Squares Mean Difference (SE) |
| Estimated Value | 0.0446 | |
| Confidence Interval |
(2-Sided) 95% 0.0073 to 0.0820 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0186 |
|
| Estimation Comments | Standard Error of the Mean Difference | |
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Tiotropium Bromide Via (Spiriva® Handihaler®), Placebo |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority | |
| Comments | Day 7 analysis | |
| Statistical Test of Hypothesis | p-Value | 0.0060 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Squares Mean Difference (SE) |
| Estimated Value | 0.0813 | |
| Confidence Interval |
(2-Sided) 95% 0.0243 to 0.1382 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0284 |
|
| Estimation Comments | Standard Error of the Mean Difference | |
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | EP-101 Via Nebulizer (eFlow®) 25 mcg, Placebo |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority | |
| Comments | Day 1 analysis | |
| Statistical Test of Hypothesis | p-Value | 0.0402 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Squares Mean Difference (SE) |
| Estimated Value | 0.0385 | |
| Confidence Interval |
(2-Sided) 95% 0.0018 to 0.0752 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0183 |
|
| Estimation Comments | Standard Error of the Mean Difference | |
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | EP-101 Via Nebulizer (eFlow®) 50 mcg, Placebo |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority | |
| Comments | Day 1 analysis | |
| Statistical Test of Hypothesis | p-Value | 0.0003 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Squares Mean Difference (SE) |
| Estimated Value | 0.0696 | |
| Confidence Interval |
(2-Sided) 95% 0.0337 to 0.1055 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0179 |
|
| Estimation Comments | Standard Error of the Mean Difference | |
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | EP-101 Via Nebulizer (eFlow®)100 mcg, Placebo |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority | |
| Comments | Day 1 analysis | |
| Statistical Test of Hypothesis | p-Value | 0.0074 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Squares Mean |
| Estimated Value | 0.0501 | |
| Confidence Interval |
(2-Sided) 95% 0.0140 to 0.0861 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0180 |
|
| Estimation Comments | ||
| Title | Standardized Change in FEV1 Area Under the Curve (AUC) (0-12hr , 12-24hr, 0-24hr) on Day 1 and Day 7 |
|---|---|
| Description | 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. |
| Time Frame | Day 1 and Day 7 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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 |
| Arm/Group Title | EP-101 Via Nebulizer (eFlow®) 25 mcg | EP-101 Via Nebulizer (eFlow®) 50 mcg | EP-101 Via Nebulizer (eFlow®)100 mcg | EP-101 Via Nebulizer (eFlow®) 200 mcg | Ipratropium Bromide Inhalation Solution | Tiotropium Bromide Via (Spiriva® Handihaler®) | Placebo |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | 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 | 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 | 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 | 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 | 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 | Tiotropium bromide via (Spiriva® Handihaler®) Tiotropium bromide via (Spiriva® Handihaler®): Tiotropium 18 µg administered once daily for 7 days using Handihaler® DPI | Placebo Placebo : Placebo administered once daily for 7 days |
| Measure Participants | 72 | 76 | 75 | 71 | 74 | 75 | 76 |
| AUC 0-12 on Day 1 |
0.1001
(0.15704)
|
0.1520
(0.13646)
|
0.1414
(0.11045)
|
0.1720
(0.12644)
|
0.1990
(0.13740)
|
0.1213
(0.12548)
|
0.0130
(0.11486)
|
| AUC 12-24 on Day 1 |
0.0039
(0.17104)
|
0.0681
(0.12835)
|
0.0413
(0.14032)
|
0.0645
(0.13275)
|
0.0987
(0.16958)
|
0.0499
(0.14532)
|
-0.0245
(0.12151)
|
| AUC 0-24 on Day 1 |
0.0525
(0.15495)
|
0.1107
(0.12207)
|
0.0919
(0.11554)
|
0.1194
(0.11905)
|
0.1496
(0.14425)
|
0.0872
(0.12638)
|
-0.0073
(0.11377)
|
| AUC 0-12 on Day 7 |
0.1034
(0.19035)
|
0.1411
(0.16343)
|
0.1329
(0.13416)
|
0.1438
(0.14833)
|
0.1603
(0.16420)
|
0.1256
(0.15197)
|
-0.0098
(0.15537)
|
| AUC 12-24 on Day 7 |
0.0112
(0.18136)
|
0.0540
(0.16633)
|
0.0278
(0.15187)
|
0.0614
(0.13450)
|
0.0357
(0.17382)
|
0.0283
(0.15596)
|
0.0698
(0.16584)
|
| AUC 0-24 on Day 7 |
0.0579
(0.17822)
|
0.0980
(0.15651)
|
0.0812
(0.13293)
|
0.1030
(0.13162)
|
0.1009
(0.15882)
|
0.0776
(0.14702)
|
-0.0395
(0.15415)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | EP-101 Via Nebulizer (eFlow®) 25 mcg, Placebo |
|---|---|---|
| Comments | ACU 0-24 on Day 1 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Squares Mean Difference (SE) |
| Estimated Value | 0.0767 | |
| Confidence Interval |
(2-Sided) 95% 0.0505 to 0.1028 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0131 |
|
| Estimation Comments | standard error of the mean difference | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | EP-101 Via Nebulizer (eFlow®) 50 mcg, Placebo |
|---|---|---|
| Comments | ACU 0-24 Day 1 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Squares Mean Difference (SE) |
| Estimated Value | 0.1220 | |
| Confidence Interval |
(2-Sided) 95% 0.0965 to 0.1475 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0127 |
|
| Estimation Comments | standard error of the Mean difference | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | EP-101 Via Nebulizer (eFlow®)100 mcg, Placebo |
|---|---|---|
| Comments | AUC 0-24 Day 1 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Squares Mean Difference (SE) |
| Estimated Value | 0.1222 | |
| Confidence Interval |
(2-Sided) 95% 0.0965 to 0.1479 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0128 |
|
| Estimation Comments | standard error of the Mean difference | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | EP-101 Via Nebulizer (eFlow®) 200 mcg, Placebo |
|---|---|---|
| Comments | AUC 0-24 day 1 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Squares Mean Difference (SE) |
| Estimated Value | 0.1625 | |
| Confidence Interval |
(2-Sided) 95% 0.1362 to 0.1888 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0131 |
|
| Estimation Comments | standard error of the Mean difference | |
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Ipratropium Bromide Inhalation Solution, Placebo |
|---|---|---|
| Comments | AUC 0-24 day 1 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Squares Mean Difference (SE) |
| Estimated Value | 0.1690 | |
| Confidence Interval |
(2-Sided) 95% 0.1434 to 0.1946 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0128 |
|
| Estimation Comments | standard error of the Mean difference | |
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Tiotropium Bromide Via (Spiriva® Handihaler®), Placebo |
|---|---|---|
| Comments | AUC 0-24 day 1 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Squares Mean Difference (SE) |
| Estimated Value | 0.1095 | |
| Confidence Interval |
(2-Sided) 95% 0.0716 to 0.1473 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0189 |
|
| Estimation Comments | standard error of the Mean difference | |
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | EP-101 Via Nebulizer (eFlow®) 25 mcg, Placebo |
|---|---|---|
| Comments | AUC 0-24 on Day 7 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Squares Mean Difference (SE) |
| Estimated Value | 0.1095 | |
| Confidence Interval |
(2-Sided) 95% 0.0812 to 0.1379 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0141 |
|
| Estimation Comments | standard error of the Mean difference | |
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | EP-101 Via Nebulizer (eFlow®) 50 mcg, Placebo |
|---|---|---|
| Comments | AUC0-24 on Day 7 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Squares Mean Difference (SE) |
| Estimated Value | 0.1271 | |
| Confidence Interval |
(2-Sided) 95% 0.0993 to 0.1548 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0139 |
|
| Estimation Comments | standard error of the Mean difference | |
Statistical Analysis 9
| Statistical Analysis Overview | Comparison Group Selection | EP-101 Via Nebulizer (eFlow®)100 mcg, Placebo |
|---|---|---|
| Comments | AUC 0-24 on day 7 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Squares Mean Difference (SE) |
| Estimated Value | 0.1450 | |
| Confidence Interval |
(2-Sided) 95% 0.1169 to 0.1730 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0140 |
|
| Estimation Comments | standard error of the Mean difference | |
Statistical Analysis 10
| Statistical Analysis Overview | Comparison Group Selection | EP-101 Via Nebulizer (eFlow®) 200 mcg, Placebo |
|---|---|---|
| Comments | AUC 0-24 on day 7 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Squares Mean Difference (SE) |
| Estimated Value | 0.1688 | |
| Confidence Interval |
(2-Sided) 95% 0.1403 to 0.1972 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0142 |
|
| Estimation Comments | standard error of the Mean difference | |
Statistical Analysis 11
| Statistical Analysis Overview | Comparison Group Selection | Ipratropium Bromide Inhalation Solution, Placebo |
|---|---|---|
| Comments | AUC 0-24 on day 7 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Squares Mean Difference (SE) |
| Estimated Value | 0.1396 | |
| Confidence Interval |
(2-Sided) 95% 0.1117 to 0.1730 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0139 |
|
| Estimation Comments | standard error of the Mean difference | |
Statistical Analysis 12
| Statistical Analysis Overview | Comparison Group Selection | Tiotropium Bromide Via (Spiriva® Handihaler®), Placebo |
|---|---|---|
| Comments | AUC 0-24 on day 7 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Squares Mean Difference (SE) |
| Estimated Value | 0.1183 | |
| Confidence Interval |
(2-Sided) 95% 0.0795 to 0.1972 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0194 |
|
| Estimation Comments | standard error of the Mean difference | |
Statistical Analysis 13
| Statistical Analysis Overview | Comparison Group Selection | EP-101 Via Nebulizer (eFlow®) 25 mcg, Placebo |
|---|---|---|
| Comments | AUC 0-12 on day 1 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Squares Mean Difference (SE) |
| Estimated Value | 0.1038 | |
| Confidence Interval |
(2-Sided) 95% 0.0776 to 0.1301 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0131 |
|
| Estimation Comments | standard error of the Mean difference | |
Statistical Analysis 14
| Statistical Analysis Overview | Comparison Group Selection | EP-101 Via Nebulizer (eFlow®) 50 mcg, Placebo |
|---|---|---|
| Comments | AUC 0-12 on day 1 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Squares Mean Difference (SE) |
| Estimated Value | 0.1468 | |
| Confidence Interval |
(2-Sided) 95% 0.1212 to 0.1724 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0128 |
|
| Estimation Comments | standard error of the Mean difference | |
Statistical Analysis 15
| Statistical Analysis Overview | Comparison Group Selection | EP-101 Via Nebulizer (eFlow®)100 mcg, Placebo |
|---|---|---|
| Comments | AUC 0-12 on day 1 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Squares Mean Difference (SE) |
| Estimated Value | 0.1579 | |
| Confidence Interval |
(2-Sided) 95% 0.1322 to 0.1837 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0128 |
|
| Estimation Comments | standard error of the Mean difference | |
Statistical Analysis 16
| Statistical Analysis Overview | Comparison Group Selection | EP-101 Via Nebulizer (eFlow®) 200 mcg, Placebo |
|---|---|---|
| Comments | AUC 0-12 on day 1 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Squares Mean Difference (SE) |
| Estimated Value | 0.1919 | |
| Confidence Interval |
(2-Sided) 95% 0.1655 to 0.2184 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0132 |
|
| Estimation Comments | standard error of the Mean difference | |
Statistical Analysis 17
| Statistical Analysis Overview | Comparison Group Selection | Ipratropium Bromide Inhalation Solution, Placebo |
|---|---|---|
| Comments | AUC 0-12 on day 1 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Squares Mean Difference (SE) |
| Estimated Value | 0.1994 | |
| Confidence Interval |
(2-Sided) 95% 0.1738 to 0.2251 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0128 |
|
| Estimation Comments | standard error of the Mean difference | |
Statistical Analysis 18
| Statistical Analysis Overview | Comparison Group Selection | Tiotropium Bromide Via (Spiriva® Handihaler®), Placebo |
|---|---|---|
| Comments | AUC 0-12 on day 1 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Squares Mean Difference (SE) |
| Estimated Value | 0.1248 | |
| Confidence Interval |
(2-Sided) 95% 0.0872 to 0.1625 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0188 |
|
| Estimation Comments | standard error of the Mean difference | |
Statistical Analysis 19
| Statistical Analysis Overview | Comparison Group Selection | EP-101 Via Nebulizer (eFlow®) 25 mcg, Placebo |
|---|---|---|
| Comments | AUC 0-12 on day 7 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | standard error of the Mean difference | |
| Method of Estimation | Estimation Parameter | Least Squares Mean Difference (SE) |
| Estimated Value | 0.1279 | |
| Confidence Interval |
(2-Sided) 95% 0.0970 to 0.1587 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0154 |
|
| Estimation Comments | standard error of the Mean difference | |
Statistical Analysis 20
| Statistical Analysis Overview | Comparison Group Selection | EP-101 Via Nebulizer (eFlow®) 50 mcg, Placebo |
|---|---|---|
| Comments | AUC 0-12 on day 7 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Squares Mean Difference (SE) |
| Estimated Value | 0.1454 | |
| Confidence Interval |
(2-Sided) 95% 0.1151 to 0.1756 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0151 |
|
| Estimation Comments | standard error of the Mean difference | |
Statistical Analysis 21
| Statistical Analysis Overview | Comparison Group Selection | EP-101 Via Nebulizer (eFlow®)100 mcg, Placebo |
|---|---|---|
| Comments | AUC 0-12 on day 7 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Squares Mean Difference (SE) |
| Estimated Value | 0.1699 | |
| Confidence Interval |
(2-Sided) 95% 0.1393 to 0.2004 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0152 |
|
| Estimation Comments | standard error of the Mean difference | |
Statistical Analysis 22
| Statistical Analysis Overview | Comparison Group Selection | EP-101 Via Nebulizer (eFlow®) 200 mcg, Placebo |
|---|---|---|
| Comments | AUC 0-12 on day 7 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Squares Mean Difference (SE) |
| Estimated Value | 0.1814 | |
| Confidence Interval |
(2-Sided) 95% 0.1503 to 0.2125 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0155 |
|
| Estimation Comments | standard error of the Mean difference | |
Statistical Analysis 23
| Statistical Analysis Overview | Comparison Group Selection | Ipratropium Bromide Inhalation Solution, Placebo |
|---|---|---|
| Comments | AUC 0-12 on day 7 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Squares Mean Difference (SE) |
| Estimated Value | 0.1697 | |
| Confidence Interval |
(2-Sided) 95% 0.1393 to 0.201 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0152 |
|
| Estimation Comments | standard error of the Mean difference | |
Statistical Analysis 24
| Statistical Analysis Overview | Comparison Group Selection | Tiotropium Bromide Via (Spiriva® Handihaler®), Placebo |
|---|---|---|
| Comments | AUC 0-12 on day 7 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Squares Mean Difference (SE) |
| Estimated Value | 0.1384 | |
| Confidence Interval |
(2-Sided) 95% 0.0951 to 0.1817 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0216 |
|
| Estimation Comments | standard error of the Mean difference | |
Statistical Analysis 25
| Statistical Analysis Overview | Comparison Group Selection | EP-101 Via Nebulizer (eFlow®) 25 mcg, Placebo |
|---|---|---|
| Comments | AUC 12-24 on day 1 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Squares Mean Difference (SE) |
| Estimated Value | 0.0471 | |
| Confidence Interval |
(2-Sided) 95% 0.0155 to 0.0786 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0157 |
|
| Estimation Comments | standard error of the Mean difference | |
Statistical Analysis 26
| Statistical Analysis Overview | Comparison Group Selection | EP-101 Via Nebulizer (eFlow®) 50 mcg, Placebo |
|---|---|---|
| Comments | AUC 12-24 on day 1 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Squares Mean Difference (SE) |
| Estimated Value | 0.0918 | |
| Confidence Interval |
(2-Sided) 95% 0.0611 to 0.1226 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0154 |
|
| Estimation Comments | standard error of the Mean difference | |
Statistical Analysis 27
| Statistical Analysis Overview | Comparison Group Selection | EP-101 Via Nebulizer (eFlow®)100 mcg, Placebo |
|---|---|---|
| Comments | AUC 12-24 on day 1 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Squares Mean Difference (SE) |
| Estimated Value | 0.0829 | |
| Confidence Interval |
(2-Sided) 95% 0.0519 to 0.1139 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0155 |
|
| Estimation Comments | standard error of the Mean difference | |
Statistical Analysis 28
| Statistical Analysis Overview | Comparison Group Selection | EP-101 Via Nebulizer (eFlow®) 200 mcg, Placebo |
|---|---|---|
| Comments | AUC 12-24 o day 1 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Squares Mean Difference (SE) |
| Estimated Value | 0.1299 | |
| Confidence Interval |
(2-Sided) 95% 0.0982 to 0.1617 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0158 |
|
| Estimation Comments | standard error of the Mean difference | |
Statistical Analysis 29
| Statistical Analysis Overview | Comparison Group Selection | Ipratropium Bromide Inhalation Solution, Placebo |
|---|---|---|
| Comments | AUC 12-24 on day 1 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Squares Mean Difference (SE) |
| Estimated Value | 0.1369 | |
| Confidence Interval |
(2-Sided) 95% 0.1061 to 0.1678 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0154 |
|
| Estimation Comments | standard error of the Mean difference | |
Statistical Analysis 30
| Statistical Analysis Overview | Comparison Group Selection | Tiotropium Bromide Via (Spiriva® Handihaler®), Placebo |
|---|---|---|
| Comments | AUC 12-24 on day 1 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Squares Mean Difference (SE) |
| Estimated Value | 0.0934 | |
| Confidence Interval |
(2-Sided) 95% 0.0490 to 0.1377 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0221 |
|
| Estimation Comments | standard error of the Mean difference | |
Statistical Analysis 31
| Statistical Analysis Overview | Comparison Group Selection | EP-101 Via Nebulizer (eFlow®) 25 mcg, Placebo |
|---|---|---|
| Comments | AUC 12-24 on day 7 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Squares Mean Difference (SE) |
| Estimated Value | 0.0879 | |
| Confidence Interval |
(2-Sided) 95% 0.0573 to 0.1186 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0153 |
|
| Estimation Comments | standard error of the Mean difference | |
Statistical Analysis 32
| Statistical Analysis Overview | Comparison Group Selection | EP-101 Via Nebulizer (eFlow®) 50 mcg, Placebo |
|---|---|---|
| Comments | AUC 12-24 on day 7 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Squares Mean Difference (SE) |
| Estimated Value | 0.1088 | |
| Confidence Interval |
(2-Sided) 95% 0.0788 to 0.1388 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0150 |
|
| Estimation Comments | standard error of the Mean difference | |
Statistical Analysis 33
| Statistical Analysis Overview | Comparison Group Selection | EP-101 Via Nebulizer (eFlow®)100 mcg, Placebo |
|---|---|---|
| Comments | AUC 12-24 on day 7 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Squares Mean Difference (SE) |
| Estimated Value | 0.1175 | |
| Confidence Interval |
(2-Sided) 95% 0.0872 to 0.1478 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0151 |
|
| Estimation Comments | standard error of the Mean difference | |
Statistical Analysis 34
| Statistical Analysis Overview | Comparison Group Selection | EP-101 Via Nebulizer (eFlow®) 200 mcg, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Squares Mean Difference (SE) |
| Estimated Value | 0.1532 | |
| Confidence Interval |
(2-Sided) 95% 0.1226 to 0.1838 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0153 |
|
| Estimation Comments | standard error of the Mean difference | |
Statistical Analysis 35
| Statistical Analysis Overview | Comparison Group Selection | Ipratropium Bromide Inhalation Solution, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Squares Mean Difference (SE) |
| Estimated Value | 0.1048 | |
| Confidence Interval |
(2-Sided) 95% 0.0747 to 0.1350 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0150 |
|
| Estimation Comments | standard error of the Mean difference | |
Statistical Analysis 36
| Statistical Analysis Overview | Comparison Group Selection | Tiotropium Bromide Via (Spiriva® Handihaler®), Placebo |
|---|---|---|
| Comments | AUC 12-24 on day 7 | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Squares Mean Difference (SE) |
| Estimated Value | 0.0993 | |
| Confidence Interval |
(2-Sided) 95% 0.0589 to 0.1398 |
|
| Parameter Dispersion |
Type: Standard Error of the Mean Value: 0.0202 |
|
| Estimation Comments | standard error of the Mean difference | |
| Title | Peak FEV1 (Maximum FEV1 During the First 4 Hours Post-dose on Day 1 and Day 7) |
|---|---|
| Description | Spirometry measurements were conducted in accordance with the current ATS/ERS 2005 guidelines |
| Time Frame | Day 1 and Day 7 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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 |
| Arm/Group Title | EP-101 Via Nebulizer (eFlow®) 25 mcg | EP-101 Via Nebulizer (eFlow®) 50 mcg | EP-101 Via Nebulizer (eFlow®)100 mcg | EP-101 Via Nebulizer (eFlow®) 200 mcg | Ipratropium Bromide Inhalation Solution | Tiotropium Bromide Via (Spiriva® Handihaler®) | Placebo |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | 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 | 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 | 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 | 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 | 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 | Tiotropium bromide via (Spiriva® Handihaler®) Tiotropium bromide via (Spiriva® Handihaler®): Tiotropium 18 µg administered once daily for 7 days using Handihaler® DPI | Placebo Placebo : Placebo administered once daily for 7 days |
| Measure Participants | 72 | 76 | 75 | 72 | 74 | 76 | 77 |
| Day 1 |
1.469
(0.5049)
|
1.498
(0.4857)
|
1.443
(0.4431)
|
1.455
(0.4355)
|
1.601
(0.4665)
|
1.434
(0.4774)
|
1.356
(0.4471)
|
| Day 7 |
1.482
(0.4993)
|
1.496
(0.4694)
|
1.462
(0.4300)
|
1.453
(0.4476)
|
1.594
(0.4943)
|
1.475
(0.4556)
|
1.348
(0.4465)
|
| Title | Treatment Responders (Number of Subjects With Clinically Meaningful Change From Pre-dose in Trough FEV1 on Day 1 and Day 7) |
|---|---|
| Description | 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. |
| Time Frame | Day 1 and Day 7 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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 |
| Arm/Group Title | EP-101 Via Nebulizer (eFlow®) 25 mcg | EP-101 Via Nebulizer (eFlow®) 50 mcg | EP-101 Via Nebulizer (eFlow®)100 mcg | EP-101 Via Nebulizer (eFlow®) 200 mcg | Ipratropium Bromide Inhalation Solution | Tiotropium Bromide Via (Spiriva® Handihaler®) |
|---|---|---|---|---|---|---|
| Arm/Group Description | 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 | 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 | 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 | 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 | 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 | Tiotropium bromide via (Spiriva® Handihaler®) Tiotropium bromide via (Spiriva® Handihaler®): Tiotropium 18 µg administered once daily for 7 days using Handihaler® DPI |
| Measure Participants | 72 | 76 | 75 | 72 | 74 | 76 |
| Day 1 |
18
12.9%
|
29
NaN
|
24
NaN
|
24
NaN
|
24
NaN
|
26
NaN
|
| Day 7 |
29
20.9%
|
30
NaN
|
34
NaN
|
37
NaN
|
27
NaN
|
37
NaN
|
| Title | Number of Participants With Adverse Events, Vital Signs, and Clinically Significant Abnormal ECG Values and Laboratory Tests |
|---|---|
| Description | 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. |
| Time Frame | Day 1 through Day 7 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All subjects who received at least one dose of study medication were included in the safety analysis. |
| Arm/Group Title | EP-101 Via Nebulizer (eFlow®) 25 mcg | EP-101 Via Nebulizer (eFlow®) 50 mcg | EP-101 Via Nebulizer (eFlow®)100 mcg | EP-101 Via Nebulizer (eFlow®) 200 mcg | Ipratropium Bromide Inhalation Solution | Tiotropium Bromide Via (Spiriva® Handihaler®) | Placebo |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | 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 | 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 | 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 | 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 | 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 | Tiotropium bromide via (Spiriva® Handihaler®) Tiotropium bromide via (Spiriva® Handihaler®): Tiotropium 18 µg administered once daily for 7 days using Handihaler® DPI | Placebo Placebo : Placebo administered once daily for 7 days |
| Measure Participants | 74 | 78 | 76 | 75 | 75 | 76 | 77 |
| Treatment emergent AEs |
23
16.5%
|
23
NaN
|
28
NaN
|
26
NaN
|
19
NaN
|
12
NaN
|
25
NaN
|
| Clinical signicant abnormal vital signs |
0
0%
|
0
NaN
|
2
NaN
|
0
NaN
|
1
NaN
|
0
NaN
|
1
NaN
|
| Clinically significant abnormal ECG values Day 1 |
10
7.2%
|
7
NaN
|
13
NaN
|
11
NaN
|
5
NaN
|
8
NaN
|
6
NaN
|
| Clinically significant abnormal ECG values Day 7 |
7
5%
|
5
NaN
|
8
NaN
|
11
NaN
|
3
NaN
|
8
NaN
|
7
NaN
|
| Clinicall significant abnormal lab valuesday1-day7 |
1
0.7%
|
0
NaN
|
2
NaN
|
2
NaN
|
1
NaN
|
0
NaN
|
3
NaN
|
| Title | Rescue Medication Use |
|---|---|
| Description | Mean number of puffs of daily rescue medication |
| Time Frame | Day 1 through Day 7 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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 |
| Arm/Group Title | EP-101 Via Nebulizer (eFlow®) 25 mcg | EP-101 Via Nebulizer (eFlow®) 50 mcg | EP-101 Via Nebulizer (eFlow®)100 mcg | EP-101 Via Nebulizer (eFlow®) 200 mcg | Ipratropium Bromide Inhalation Solution | Tiotropium Bromide Via (Spiriva® Handihaler®) | Placebo |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | 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 | 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 | 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 | 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 | 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 | Tiotropium bromide via (Spiriva® Handihaler®) Tiotropium bromide via (Spiriva® Handihaler®): Tiotropium 18 µg administered once daily for 7 days using Handihaler® DPI | Placebo Placebo : Placebo administered once daily for 7 days |
| Measure Participants | 72 | 76 | 75 | 72 | 74 | 76 | 77 |
| Mean (Standard Deviation) [average daily number of puffs] |
1.34
(2.72)
|
1.11
(1.89)
|
1.48
(2.43)
|
1.29
(2.70)
|
1.42
(2.91)
|
1.33
(3.01)
|
1.59
(2.16)
|
| Title | Treatment Responders (Percentage of Subjects With Clinically Meaningful Change From Pre-dose in Trough FEV1 on Day 1 and Day 7) |
|---|---|
| Description | 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. |
| Time Frame | Day 1 and Day 7 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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 |
| Arm/Group Title | EP-101 Via Nebulizer (eFlow®) 25 mcg | EP-101 Via Nebulizer (eFlow®) 50 mcg | EP-101 Via Nebulizer (eFlow®)100 mcg | EP-101 Via Nebulizer (eFlow®) 200 mcg | Ipratropium Bromide Inhalation Solution | Tiotropium Bromide Via (Spiriva® Handihaler®) |
|---|---|---|---|---|---|---|
| Arm/Group Description | 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 | 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 | 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 | 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 | 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 | Tiotropium bromide via (Spiriva® Handihaler®) Tiotropium bromide via (Spiriva® Handihaler®): Tiotropium 18 µg administered once daily for 7 days using Handihaler® DPI |
| Measure Participants | 72 | 76 | 75 | 72 | 74 | 76 |
| Day 1 |
25.0
18%
|
38.7
NaN
|
32.0
NaN
|
35.3
NaN
|
33.8
NaN
|
34.7
NaN
|
| Day 7 |
40.3
29%
|
40.0
NaN
|
46.6
NaN
|
51.4
NaN
|
37.5
NaN
|
48.7
NaN
|
Adverse Events
| Time Frame | day 1 through day 7 | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | existing conditions which worsen or events which occur during the course of the clinical trial after treatment with randomized study drug has started | |||||||||||||
| Arm/Group Title | EP-101 Via Nebulizer (eFlow®) 25 mcg | EP-101 Via Nebulizer (eFlow®) 50 mcg | EP-101 Via Nebulizer (eFlow®)100 mcg | EP-101 Via Nebulizer (eFlow®) 200 mcg | Ipratropium Bromide Inhalation Solution | Tiotropium Bromide Via (Spiriva® Handihaler®) | Placebo | |||||||
| Arm/Group Description | 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 | 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 | 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 | 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 | 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 | Tiotropium bromide via (Spiriva® Handihaler®) Tiotropium bromide via (Spiriva® Handihaler®): Tiotropium 18 µg administered once daily for 7 days using Handihaler® DPI | Placebo Placebo : Placebo administered once daily for 7 days | |||||||
All Cause Mortality |
||||||||||||||
| EP-101 Via Nebulizer (eFlow®) 25 mcg | EP-101 Via Nebulizer (eFlow®) 50 mcg | EP-101 Via Nebulizer (eFlow®)100 mcg | EP-101 Via Nebulizer (eFlow®) 200 mcg | Ipratropium Bromide Inhalation Solution | Tiotropium Bromide Via (Spiriva® Handihaler®) | Placebo | ||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/74 (0%) | 0/78 (0%) | 0/76 (0%) | 0/75 (0%) | 0/75 (0%) | 0/76 (0%) | 0/77 (0%) | |||||||
Serious Adverse Events |
||||||||||||||
| EP-101 Via Nebulizer (eFlow®) 25 mcg | EP-101 Via Nebulizer (eFlow®) 50 mcg | EP-101 Via Nebulizer (eFlow®)100 mcg | EP-101 Via Nebulizer (eFlow®) 200 mcg | Ipratropium Bromide Inhalation Solution | Tiotropium Bromide Via (Spiriva® Handihaler®) | Placebo | ||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 8/74 (10.8%) | 13/78 (16.7%) | 14/76 (18.4%) | 13/75 (17.3%) | 5/75 (6.7%) | 2/76 (2.6%) | 16/77 (20.8%) | |||||||
| Nervous system disorders | ||||||||||||||
| headache | 3/74 (4.1%) | 4 | 3/78 (3.8%) | 5 | 5/76 (6.6%) | 5 | 4/75 (5.3%) | 7 | 0/75 (0%) | 0 | 2/76 (2.6%) | 3 | 7/77 (9.1%) | 9 |
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||
| cough | 5/74 (6.8%) | 9 | 10/78 (12.8%) | 13 | 9/76 (11.8%) | 15 | 9/75 (12%) | 14 | 5/75 (6.7%) | 5 | 1/76 (1.3%) | 1 | 9/77 (11.7%) | 14 |
Other (Not Including Serious) Adverse Events |
||||||||||||||
| EP-101 Via Nebulizer (eFlow®) 25 mcg | EP-101 Via Nebulizer (eFlow®) 50 mcg | EP-101 Via Nebulizer (eFlow®)100 mcg | EP-101 Via Nebulizer (eFlow®) 200 mcg | Ipratropium Bromide Inhalation Solution | Tiotropium Bromide Via (Spiriva® Handihaler®) | Placebo | ||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/74 (0%) | 0/78 (0%) | 0/76 (0%) | 0/75 (0%) | 0/75 (0%) | 0/76 (0%) | 0/77 (0%) | |||||||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
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.
Results Point of Contact
| Name/Title | Respiratory Medical Director |
|---|---|
| Organization | Sunovion Pharmaceuticals Inc. |
| Phone | 1-866-503-6351 |
Responsible Party:
Sunovion Respiratory Development Inc.
ClinicalTrials.gov Identifier:
NCT01426009
Other Study ID Numbers:
- EP-101-03
First Posted:
Aug 30, 2011
Last Update Posted:
May 9, 2018
Last Verified:
May 1, 2018