Chronic Obstructive Pulmonary Disease
Conditions
Keywords
COPD
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).
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.
Interventions
DRUGEP-101 via nebulizer (eFlow®) 200 ug
EP-101 (200) ug administered once daily for 7 days
DRUGEP-101 via nebulizer (eFlow®) 25 ug
EP-101 (25 ug ) Dose 1 administered once daily for 7 days
DRUGEP-101 via nebulizer (eFlow®) 50 ug
EP-101 (50 ug ) administered once daily for 7 days
DRUGEP-101 via nebulizer (eFlow®) 100 ug
EP-101 (100ug) administered once daily for 7 days
DRUGPlacebo EP-101
Placebo EP-101 administered once daily for 7 days
DRUGTiotropium bromide via (Spiriva® Handihaler®)
Tiotropium 18 µg administered once daily for 7 days using Handihaler® DPI
DRUGIpratropium bromide Inhalation Solution via Handihaler® DPI
Ipratropium 500 µg administered three times daily for 7 days using general purpose nebulizer
Sponsors
Sunovion Respiratory Development Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to 75 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| Rescue Medication Use | Day 1 through Day 7 | Mean number of puffs of daily rescue medication |
| 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. |
| 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 |
Countries
United Kingdom, United States
Participant flow
Pre-assignment details
One randomized subject did not receive any study medication.
Participants by arm
| Arm | Count |
|---|---|
| Total Particiants total of all participants in the study | 139 |
| Total | 139 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Period 1-First Intervention (7 Days) | Adverse Event | 1 |
| Period 1-First Intervention (7 Days) | Personal Reasons | 1 |
| Period 2-Second Intervention (7 Days) | Adverse Event | 4 |
| Period 2-Second Intervention (7 Days) | personal reasons | 1 |
| Period 4-Fourth Intervention (7 Days) | personal reasons | 1 |
| Washout 1 | Personal Reasons | 1 |
| Washout 1 | Withdrawal by Subject | 1 |
| Washout 2 | electrive surgery | 1 |
| Washout 3 | personal reasons | 1 |
| Washout 4 | Lost to Follow-up | 1 |
Baseline characteristics
| Characteristic | Total Particiants |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 51 Participants |
| Age, Categorical Between 18 and 65 years | 88 Participants |
| Age, Continuous | 61.4 years STANDARD_DEVIATION 8.11 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 138 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 134 Participants |
| Region of Enrollment United Kingdom | 19 Participants |
| Region of Enrollment United States | 120 Participants |
| Sex: Female, Male Female | 78 Participants |
| Sex: Female, Male Male | 61 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 74 | 0 / 78 | 0 / 76 | 0 / 75 | 0 / 75 | 0 / 76 | 0 / 77 |
| other Total, other adverse events | 0 / 74 | 0 / 78 | 0 / 76 | 0 / 75 | 0 / 75 | 0 / 76 | 0 / 77 |
| serious Total, serious adverse events | 8 / 74 | 13 / 78 | 14 / 76 | 13 / 75 | 5 / 75 | 2 / 76 | 16 / 77 |
Outcome results
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.
Time frame: Day 1 and Day 7
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| EP-101 Via Nebulizer (eFlow®) 25 mcg | Mean Change in 24 Post Dose Trough Forced Expiratory Volume in 1 Second (FEV1) | Trough FEV1 - day 1 | 0.0477 liters | Standard Deviation 0.16359 |
| EP-101 Via Nebulizer (eFlow®) 25 mcg | Mean Change in 24 Post Dose Trough Forced Expiratory Volume in 1 Second (FEV1) | Trough FEV1 - day 7 | 0.0478 liters | Standard Deviation 0.18965 |
| EP-101 Via Nebulizer (eFlow®) 50 mcg | Mean Change in 24 Post Dose Trough Forced Expiratory Volume in 1 Second (FEV1) | Trough FEV1 - day 1 | 0.1009 liters | Standard Deviation 0.13261 |
| EP-101 Via Nebulizer (eFlow®) 50 mcg | Mean Change in 24 Post Dose Trough Forced Expiratory Volume in 1 Second (FEV1) | Trough FEV1 - day 7 | 0.0699 liters | Standard Deviation 0.16909 |
| EP-101 Via Nebulizer (eFlow®)100 mcg | Mean Change in 24 Post Dose Trough Forced Expiratory Volume in 1 Second (FEV1) | Trough FEV1 - day 1 | 0.0648 liters | Standard Deviation 0.14239 |
| EP-101 Via Nebulizer (eFlow®)100 mcg | Mean Change in 24 Post Dose Trough Forced Expiratory Volume in 1 Second (FEV1) | Trough FEV1 - day 7 | 0.0666 liters | Standard Deviation 0.15132 |
| EP-101 Via Nebulizer (eFlow®) 200 mcg | Mean Change in 24 Post Dose Trough Forced Expiratory Volume in 1 Second (FEV1) | Trough FEV1 - day 1 | 0.0632 liters | Standard Deviation 0.14965 |
| EP-101 Via Nebulizer (eFlow®) 200 mcg | Mean Change in 24 Post Dose Trough Forced Expiratory Volume in 1 Second (FEV1) | Trough FEV1 - day 7 | 0.0840 liters | Standard Deviation 0.13842 |
| Ipratropium Bromide Inhalation Solution | Mean Change in 24 Post Dose Trough Forced Expiratory Volume in 1 Second (FEV1) | Trough FEV1 - day 1 | 0.0933 liters | Standard Deviation 0.1898 |
| Ipratropium Bromide Inhalation Solution | Mean Change in 24 Post Dose Trough Forced Expiratory Volume in 1 Second (FEV1) | Trough FEV1 - day 7 | 0.0292 liters | Standard Deviation 0.16507 |
| Tiotropium Bromide Via (Spiriva® Handihaler®) | Mean Change in 24 Post Dose Trough Forced Expiratory Volume in 1 Second (FEV1) | Trough FEV1 - day 1 | 0.0740 liters | Standard Deviation 0.144441 |
| Tiotropium Bromide Via (Spiriva® Handihaler®) | Mean Change in 24 Post Dose Trough Forced Expiratory Volume in 1 Second (FEV1) | Trough FEV1 - day 7 | 0.0564 liters | Standard Deviation 0.16356 |
| Placebo | Mean Change in 24 Post Dose Trough Forced Expiratory Volume in 1 Second (FEV1) | Trough FEV1 - day 1 | 0.0301 liters | Standard Deviation 0.14394 |
| Placebo | Mean Change in 24 Post Dose Trough Forced Expiratory Volume in 1 Second (FEV1) | Trough FEV1 - day 7 | -0.155 liters | Standard Deviation 0.17934 |
Comparison: 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.p-value: 0.000395% CI: [0.0347, 0.1099]ANCOVA
Comparison: 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.p-value: 0.000695% CI: [0.0307, 0.1046]ANCOVA
Comparison: 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.p-value: <0.000195% CI: [0.0644, 0.1398]ANCOVA
Comparison: 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.p-value: <0.000195% CI: [0.0918, 0.1681]ANCOVA
Comparison: 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.p-value: 0.0295% CI: [0.0073, 0.082]Mantel Haenszel
Comparison: 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.p-value: 0.00695% CI: [0.0243, 0.1382]ANCOVA
Comparison: 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.p-value: 0.040295% CI: [0.0018, 0.0752]ANCOVA
Comparison: 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.p-value: 0.000395% CI: [0.0337, 0.1055]ANCOVA
Comparison: 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.p-value: 0.007495% CI: [0.014, 0.0861]ANCOVA
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.
Time frame: Day 1 and Day 7
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| EP-101 Via Nebulizer (eFlow®) 25 mcg | Standardized Change in FEV1 Area Under the Curve (AUC) (0-12hr , 12-24hr, 0-24hr) on Day 1 and Day 7 | AUC 0-12 on Day 7 | 0.1034 liters | Standard Deviation 0.19035 |
| EP-101 Via Nebulizer (eFlow®) 25 mcg | Standardized Change in FEV1 Area Under the Curve (AUC) (0-12hr , 12-24hr, 0-24hr) on Day 1 and Day 7 | AUC 0-12 on Day 1 | 0.1001 liters | Standard Deviation 0.15704 |
| EP-101 Via Nebulizer (eFlow®) 25 mcg | Standardized Change in FEV1 Area Under the Curve (AUC) (0-12hr , 12-24hr, 0-24hr) on Day 1 and Day 7 | AUC 12-24 on Day 7 | 0.0112 liters | Standard Deviation 0.18136 |
| EP-101 Via Nebulizer (eFlow®) 25 mcg | Standardized Change in FEV1 Area Under the Curve (AUC) (0-12hr , 12-24hr, 0-24hr) on Day 1 and Day 7 | AUC 0-24 on Day 1 | 0.0525 liters | Standard Deviation 0.15495 |
| EP-101 Via Nebulizer (eFlow®) 25 mcg | Standardized Change in FEV1 Area Under the Curve (AUC) (0-12hr , 12-24hr, 0-24hr) on Day 1 and Day 7 | AUC 0-24 on Day 7 | 0.0579 liters | Standard Deviation 0.17822 |
| EP-101 Via Nebulizer (eFlow®) 25 mcg | Standardized Change in FEV1 Area Under the Curve (AUC) (0-12hr , 12-24hr, 0-24hr) on Day 1 and Day 7 | AUC 12-24 on Day 1 | 0.0039 liters | Standard Deviation 0.17104 |
| EP-101 Via Nebulizer (eFlow®) 50 mcg | Standardized Change in FEV1 Area Under the Curve (AUC) (0-12hr , 12-24hr, 0-24hr) on Day 1 and Day 7 | AUC 12-24 on Day 7 | 0.0540 liters | Standard Deviation 0.16633 |
| EP-101 Via Nebulizer (eFlow®) 50 mcg | Standardized Change in FEV1 Area Under the Curve (AUC) (0-12hr , 12-24hr, 0-24hr) on Day 1 and Day 7 | AUC 0-12 on Day 1 | 0.1520 liters | Standard Deviation 0.13646 |
| EP-101 Via Nebulizer (eFlow®) 50 mcg | Standardized Change in FEV1 Area Under the Curve (AUC) (0-12hr , 12-24hr, 0-24hr) on Day 1 and Day 7 | AUC 12-24 on Day 1 | 0.0681 liters | Standard Deviation 0.12835 |
| EP-101 Via Nebulizer (eFlow®) 50 mcg | Standardized Change in FEV1 Area Under the Curve (AUC) (0-12hr , 12-24hr, 0-24hr) on Day 1 and Day 7 | AUC 0-24 on Day 7 | 0.0980 liters | Standard Deviation 0.15651 |
| EP-101 Via Nebulizer (eFlow®) 50 mcg | Standardized Change in FEV1 Area Under the Curve (AUC) (0-12hr , 12-24hr, 0-24hr) on Day 1 and Day 7 | AUC 0-12 on Day 7 | 0.1411 liters | Standard Deviation 0.16343 |
| EP-101 Via Nebulizer (eFlow®) 50 mcg | Standardized Change in FEV1 Area Under the Curve (AUC) (0-12hr , 12-24hr, 0-24hr) on Day 1 and Day 7 | AUC 0-24 on Day 1 | 0.1107 liters | Standard Deviation 0.12207 |
| EP-101 Via Nebulizer (eFlow®)100 mcg | Standardized Change in FEV1 Area Under the Curve (AUC) (0-12hr , 12-24hr, 0-24hr) on Day 1 and Day 7 | AUC 12-24 on Day 1 | 0.0413 liters | Standard Deviation 0.14032 |
| EP-101 Via Nebulizer (eFlow®)100 mcg | Standardized Change in FEV1 Area Under the Curve (AUC) (0-12hr , 12-24hr, 0-24hr) on Day 1 and Day 7 | AUC 0-24 on Day 7 | 0.0812 liters | Standard Deviation 0.13293 |
| EP-101 Via Nebulizer (eFlow®)100 mcg | Standardized Change in FEV1 Area Under the Curve (AUC) (0-12hr , 12-24hr, 0-24hr) on Day 1 and Day 7 | AUC 0-24 on Day 1 | 0.0919 liters | Standard Deviation 0.11554 |
| EP-101 Via Nebulizer (eFlow®)100 mcg | Standardized Change in FEV1 Area Under the Curve (AUC) (0-12hr , 12-24hr, 0-24hr) on Day 1 and Day 7 | AUC 12-24 on Day 7 | 0.0278 liters | Standard Deviation 0.15187 |
| EP-101 Via Nebulizer (eFlow®)100 mcg | Standardized Change in FEV1 Area Under the Curve (AUC) (0-12hr , 12-24hr, 0-24hr) on Day 1 and Day 7 | AUC 0-12 on Day 1 | 0.1414 liters | Standard Deviation 0.11045 |
| EP-101 Via Nebulizer (eFlow®)100 mcg | Standardized Change in FEV1 Area Under the Curve (AUC) (0-12hr , 12-24hr, 0-24hr) on Day 1 and Day 7 | AUC 0-12 on Day 7 | 0.1329 liters | Standard Deviation 0.13416 |
| EP-101 Via Nebulizer (eFlow®) 200 mcg | Standardized Change in FEV1 Area Under the Curve (AUC) (0-12hr , 12-24hr, 0-24hr) on Day 1 and Day 7 | AUC 12-24 on Day 7 | 0.0614 liters | Standard Deviation 0.1345 |
| EP-101 Via Nebulizer (eFlow®) 200 mcg | Standardized Change in FEV1 Area Under the Curve (AUC) (0-12hr , 12-24hr, 0-24hr) on Day 1 and Day 7 | AUC 0-12 on Day 1 | 0.1720 liters | Standard Deviation 0.12644 |
| EP-101 Via Nebulizer (eFlow®) 200 mcg | Standardized Change in FEV1 Area Under the Curve (AUC) (0-12hr , 12-24hr, 0-24hr) on Day 1 and Day 7 | AUC 12-24 on Day 1 | 0.0645 liters | Standard Deviation 0.13275 |
| EP-101 Via Nebulizer (eFlow®) 200 mcg | Standardized Change in FEV1 Area Under the Curve (AUC) (0-12hr , 12-24hr, 0-24hr) on Day 1 and Day 7 | AUC 0-24 on Day 1 | 0.1194 liters | Standard Deviation 0.11905 |
| EP-101 Via Nebulizer (eFlow®) 200 mcg | Standardized Change in FEV1 Area Under the Curve (AUC) (0-12hr , 12-24hr, 0-24hr) on Day 1 and Day 7 | AUC 0-12 on Day 7 | 0.1438 liters | Standard Deviation 0.14833 |
| EP-101 Via Nebulizer (eFlow®) 200 mcg | Standardized Change in FEV1 Area Under the Curve (AUC) (0-12hr , 12-24hr, 0-24hr) on Day 1 and Day 7 | AUC 0-24 on Day 7 | 0.1030 liters | Standard Deviation 0.13162 |
| Ipratropium Bromide Inhalation Solution | Standardized Change in FEV1 Area Under the Curve (AUC) (0-12hr , 12-24hr, 0-24hr) on Day 1 and Day 7 | AUC 0-12 on Day 7 | 0.1603 liters | Standard Deviation 0.1642 |
| Ipratropium Bromide Inhalation Solution | Standardized Change in FEV1 Area Under the Curve (AUC) (0-12hr , 12-24hr, 0-24hr) on Day 1 and Day 7 | AUC 12-24 on Day 1 | 0.0987 liters | Standard Deviation 0.16958 |
| Ipratropium Bromide Inhalation Solution | Standardized Change in FEV1 Area Under the Curve (AUC) (0-12hr , 12-24hr, 0-24hr) on Day 1 and Day 7 | AUC 12-24 on Day 7 | 0.0357 liters | Standard Deviation 0.17382 |
| Ipratropium Bromide Inhalation Solution | Standardized Change in FEV1 Area Under the Curve (AUC) (0-12hr , 12-24hr, 0-24hr) on Day 1 and Day 7 | AUC 0-24 on Day 1 | 0.1496 liters | Standard Deviation 0.14425 |
| Ipratropium Bromide Inhalation Solution | Standardized Change in FEV1 Area Under the Curve (AUC) (0-12hr , 12-24hr, 0-24hr) on Day 1 and Day 7 | AUC 0-12 on Day 1 | 0.1990 liters | Standard Deviation 0.1374 |
| Ipratropium Bromide Inhalation Solution | Standardized Change in FEV1 Area Under the Curve (AUC) (0-12hr , 12-24hr, 0-24hr) on Day 1 and Day 7 | AUC 0-24 on Day 7 | 0.1009 liters | Standard Deviation 0.15882 |
| Tiotropium Bromide Via (Spiriva® Handihaler®) | Standardized Change in FEV1 Area Under the Curve (AUC) (0-12hr , 12-24hr, 0-24hr) on Day 1 and Day 7 | AUC 0-24 on Day 1 | 0.0872 liters | Standard Deviation 0.12638 |
| Tiotropium Bromide Via (Spiriva® Handihaler®) | Standardized Change in FEV1 Area Under the Curve (AUC) (0-12hr , 12-24hr, 0-24hr) on Day 1 and Day 7 | AUC 0-24 on Day 7 | 0.0776 liters | Standard Deviation 0.14702 |
| Tiotropium Bromide Via (Spiriva® Handihaler®) | Standardized Change in FEV1 Area Under the Curve (AUC) (0-12hr , 12-24hr, 0-24hr) on Day 1 and Day 7 | AUC 0-12 on Day 7 | 0.1256 liters | Standard Deviation 0.15197 |
| Tiotropium Bromide Via (Spiriva® Handihaler®) | Standardized Change in FEV1 Area Under the Curve (AUC) (0-12hr , 12-24hr, 0-24hr) on Day 1 and Day 7 | AUC 12-24 on Day 1 | 0.0499 liters | Standard Deviation 0.14532 |
| Tiotropium Bromide Via (Spiriva® Handihaler®) | Standardized Change in FEV1 Area Under the Curve (AUC) (0-12hr , 12-24hr, 0-24hr) on Day 1 and Day 7 | AUC 12-24 on Day 7 | 0.0283 liters | Standard Deviation 0.15596 |
| Tiotropium Bromide Via (Spiriva® Handihaler®) | Standardized Change in FEV1 Area Under the Curve (AUC) (0-12hr , 12-24hr, 0-24hr) on Day 1 and Day 7 | AUC 0-12 on Day 1 | 0.1213 liters | Standard Deviation 0.12548 |
| Placebo | Standardized Change in FEV1 Area Under the Curve (AUC) (0-12hr , 12-24hr, 0-24hr) on Day 1 and Day 7 | AUC 12-24 on Day 1 | -0.0245 liters | Standard Deviation 0.12151 |
| Placebo | Standardized Change in FEV1 Area Under the Curve (AUC) (0-12hr , 12-24hr, 0-24hr) on Day 1 and Day 7 | AUC 12-24 on Day 7 | 0.0698 liters | Standard Deviation 0.16584 |
| Placebo | Standardized Change in FEV1 Area Under the Curve (AUC) (0-12hr , 12-24hr, 0-24hr) on Day 1 and Day 7 | AUC 0-24 on Day 7 | -0.0395 liters | Standard Deviation 0.15415 |
| Placebo | Standardized Change in FEV1 Area Under the Curve (AUC) (0-12hr , 12-24hr, 0-24hr) on Day 1 and Day 7 | AUC 0-12 on Day 7 | -0.0098 liters | Standard Deviation 0.15537 |
| Placebo | Standardized Change in FEV1 Area Under the Curve (AUC) (0-12hr , 12-24hr, 0-24hr) on Day 1 and Day 7 | AUC 0-24 on Day 1 | -0.0073 liters | Standard Deviation 0.11377 |
| Placebo | Standardized Change in FEV1 Area Under the Curve (AUC) (0-12hr , 12-24hr, 0-24hr) on Day 1 and Day 7 | AUC 0-12 on Day 1 | 0.0130 liters | Standard Deviation 0.11486 |
Comparison: ACU 0-24 on Day 1p-value: <0.000195% CI: [0.0505, 0.1028]ANCOVA
Comparison: ACU 0-24 Day 1p-value: <0.000195% CI: [0.0965, 0.1475]ANCOVA
Comparison: AUC 0-24 Day 1p-value: <0.000195% CI: [0.0965, 0.1479]ANCOVA
Comparison: AUC 0-24 day 1p-value: <0.000195% CI: [0.1362, 0.1888]ANCOVA
Comparison: AUC 0-24 day 1p-value: <0.000195% CI: [0.1434, 0.1946]ANCOVA
Comparison: AUC 0-24 day 1p-value: <0.000195% CI: [0.0716, 0.1473]ANCOVA
Comparison: AUC 0-24 on Day 7p-value: <0.000195% CI: [0.0812, 0.1379]ANCOVA
Comparison: AUC0-24 on Day 7p-value: <0.000195% CI: [0.0993, 0.1548]ANCOVA
Comparison: AUC 0-24 on day 7p-value: <0.000195% CI: [0.1169, 0.173]ANCOVA
Comparison: AUC 0-24 on day 7p-value: <0.000195% CI: [0.1403, 0.1972]ANCOVA
Comparison: AUC 0-24 on day 7p-value: <0.000195% CI: [0.1117, 0.173]ANCOVA
Comparison: AUC 0-24 on day 7p-value: <0.000195% CI: [0.0795, 0.1972]ANCOVA
Comparison: AUC 0-12 on day 1p-value: <0.000195% CI: [0.0776, 0.1301]ANCOVA
Comparison: AUC 0-12 on day 1p-value: <0.000195% CI: [0.1212, 0.1724]ANCOVA
Comparison: AUC 0-12 on day 1p-value: <0.000195% CI: [0.1322, 0.1837]ANCOVA
Comparison: AUC 0-12 on day 1p-value: <0.000195% CI: [0.1655, 0.2184]ANCOVA
Comparison: AUC 0-12 on day 1p-value: <0.000195% CI: [0.1738, 0.2251]ANCOVA
Comparison: AUC 0-12 on day 1p-value: <0.000195% CI: [0.0872, 0.1625]ANCOVA
Comparison: AUC 0-12 on day 7p-value: <0.000195% CI: [0.097, 0.1587]ANCOVA
Comparison: AUC 0-12 on day 7p-value: <0.000195% CI: [0.1151, 0.1756]ANCOVA
Comparison: AUC 0-12 on day 7p-value: <0.000195% CI: [0.1393, 0.2004]ANCOVA
Comparison: AUC 0-12 on day 7p-value: <0.000195% CI: [0.1503, 0.2125]ANCOVA
Comparison: AUC 0-12 on day 7p-value: <0.000195% CI: [0.1393, 0.201]ANCOVA
Comparison: AUC 0-12 on day 7p-value: <0.000195% CI: [0.0951, 0.1817]ANCOVA
Comparison: AUC 12-24 on day 1p-value: <0.000195% CI: [0.0155, 0.0786]ANCOVA
Comparison: AUC 12-24 on day 1p-value: <0.000195% CI: [0.0611, 0.1226]ANCOVA
Comparison: AUC 12-24 on day 1p-value: <0.000195% CI: [0.0519, 0.1139]ANCOVA
Comparison: AUC 12-24 o day 1p-value: <0.000195% CI: [0.0982, 0.1617]ANCOVA
Comparison: AUC 12-24 on day 1p-value: <0.000195% CI: [0.1061, 0.1678]ANCOVA
Comparison: AUC 12-24 on day 1p-value: <0.000195% CI: [0.049, 0.1377]ANCOVA
Comparison: AUC 12-24 on day 7p-value: <0.000195% CI: [0.0573, 0.1186]ANCOVA
Comparison: AUC 12-24 on day 7p-value: <0.000195% CI: [0.0788, 0.1388]ANCOVA
Comparison: AUC 12-24 on day 7p-value: <0.000195% CI: [0.0872, 0.1478]ANCOVA
p-value: <0.000195% CI: [0.1226, 0.1838]ANCOVA
p-value: <0.000195% CI: [0.0747, 0.135]ANCOVA
Comparison: AUC 12-24 on day 7p-value: <0.000195% CI: [0.0589, 0.1398]ANCOVA
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.
Time frame: Day 1 through Day 7
Population: All subjects who received at least one dose of study medication were included in the safety analysis.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| EP-101 Via Nebulizer (eFlow®) 25 mcg | Number of Participants With Adverse Events, Vital Signs, and Clinically Significant Abnormal ECG Values and Laboratory Tests | Treatment emergent AEs | 23 Participants |
| EP-101 Via Nebulizer (eFlow®) 25 mcg | Number of Participants With Adverse Events, Vital Signs, and Clinically Significant Abnormal ECG Values and Laboratory Tests | Clinical signicant abnormal vital signs | 0 Participants |
| EP-101 Via Nebulizer (eFlow®) 25 mcg | Number of Participants With Adverse Events, Vital Signs, and Clinically Significant Abnormal ECG Values and Laboratory Tests | Clinicall significant abnormal lab valuesday1-day7 | 1 Participants |
| EP-101 Via Nebulizer (eFlow®) 25 mcg | Number of Participants With Adverse Events, Vital Signs, and Clinically Significant Abnormal ECG Values and Laboratory Tests | Clinically significant abnormal ECG values Day 7 | 7 Participants |
| EP-101 Via Nebulizer (eFlow®) 25 mcg | Number of Participants With Adverse Events, Vital Signs, and Clinically Significant Abnormal ECG Values and Laboratory Tests | Clinically significant abnormal ECG values Day 1 | 10 Participants |
| EP-101 Via Nebulizer (eFlow®) 50 mcg | Number of Participants With Adverse Events, Vital Signs, and Clinically Significant Abnormal ECG Values and Laboratory Tests | Clinical signicant abnormal vital signs | 0 Participants |
| EP-101 Via Nebulizer (eFlow®) 50 mcg | Number of Participants With Adverse Events, Vital Signs, and Clinically Significant Abnormal ECG Values and Laboratory Tests | Treatment emergent AEs | 23 Participants |
| EP-101 Via Nebulizer (eFlow®) 50 mcg | Number of Participants With Adverse Events, Vital Signs, and Clinically Significant Abnormal ECG Values and Laboratory Tests | Clinically significant abnormal ECG values Day 1 | 7 Participants |
| EP-101 Via Nebulizer (eFlow®) 50 mcg | Number of Participants With Adverse Events, Vital Signs, and Clinically Significant Abnormal ECG Values and Laboratory Tests | Clinically significant abnormal ECG values Day 7 | 5 Participants |
| EP-101 Via Nebulizer (eFlow®) 50 mcg | Number of Participants With Adverse Events, Vital Signs, and Clinically Significant Abnormal ECG Values and Laboratory Tests | Clinicall significant abnormal lab valuesday1-day7 | 0 Participants |
| EP-101 Via Nebulizer (eFlow®)100 mcg | Number of Participants With Adverse Events, Vital Signs, and Clinically Significant Abnormal ECG Values and Laboratory Tests | Clinically significant abnormal ECG values Day 7 | 8 Participants |
| EP-101 Via Nebulizer (eFlow®)100 mcg | Number of Participants With Adverse Events, Vital Signs, and Clinically Significant Abnormal ECG Values and Laboratory Tests | Clinicall significant abnormal lab valuesday1-day7 | 2 Participants |
| EP-101 Via Nebulizer (eFlow®)100 mcg | Number of Participants With Adverse Events, Vital Signs, and Clinically Significant Abnormal ECG Values and Laboratory Tests | Clinical signicant abnormal vital signs | 2 Participants |
| EP-101 Via Nebulizer (eFlow®)100 mcg | Number of Participants With Adverse Events, Vital Signs, and Clinically Significant Abnormal ECG Values and Laboratory Tests | Clinically significant abnormal ECG values Day 1 | 13 Participants |
| EP-101 Via Nebulizer (eFlow®)100 mcg | Number of Participants With Adverse Events, Vital Signs, and Clinically Significant Abnormal ECG Values and Laboratory Tests | Treatment emergent AEs | 28 Participants |
| EP-101 Via Nebulizer (eFlow®) 200 mcg | Number of Participants With Adverse Events, Vital Signs, and Clinically Significant Abnormal ECG Values and Laboratory Tests | Treatment emergent AEs | 26 Participants |
| EP-101 Via Nebulizer (eFlow®) 200 mcg | Number of Participants With Adverse Events, Vital Signs, and Clinically Significant Abnormal ECG Values and Laboratory Tests | Clinical signicant abnormal vital signs | 0 Participants |
| EP-101 Via Nebulizer (eFlow®) 200 mcg | Number of Participants With Adverse Events, Vital Signs, and Clinically Significant Abnormal ECG Values and Laboratory Tests | Clinically significant abnormal ECG values Day 7 | 11 Participants |
| EP-101 Via Nebulizer (eFlow®) 200 mcg | Number of Participants With Adverse Events, Vital Signs, and Clinically Significant Abnormal ECG Values and Laboratory Tests | Clinicall significant abnormal lab valuesday1-day7 | 2 Participants |
| EP-101 Via Nebulizer (eFlow®) 200 mcg | Number of Participants With Adverse Events, Vital Signs, and Clinically Significant Abnormal ECG Values and Laboratory Tests | Clinically significant abnormal ECG values Day 1 | 11 Participants |
| Ipratropium Bromide Inhalation Solution | Number of Participants With Adverse Events, Vital Signs, and Clinically Significant Abnormal ECG Values and Laboratory Tests | Clinically significant abnormal ECG values Day 7 | 3 Participants |
| Ipratropium Bromide Inhalation Solution | Number of Participants With Adverse Events, Vital Signs, and Clinically Significant Abnormal ECG Values and Laboratory Tests | Clinicall significant abnormal lab valuesday1-day7 | 1 Participants |
| Ipratropium Bromide Inhalation Solution | Number of Participants With Adverse Events, Vital Signs, and Clinically Significant Abnormal ECG Values and Laboratory Tests | Clinical signicant abnormal vital signs | 1 Participants |
| Ipratropium Bromide Inhalation Solution | Number of Participants With Adverse Events, Vital Signs, and Clinically Significant Abnormal ECG Values and Laboratory Tests | Treatment emergent AEs | 19 Participants |
| Ipratropium Bromide Inhalation Solution | Number of Participants With Adverse Events, Vital Signs, and Clinically Significant Abnormal ECG Values and Laboratory Tests | Clinically significant abnormal ECG values Day 1 | 5 Participants |
| Tiotropium Bromide Via (Spiriva® Handihaler®) | Number of Participants With Adverse Events, Vital Signs, and Clinically Significant Abnormal ECG Values and Laboratory Tests | Clinicall significant abnormal lab valuesday1-day7 | 0 Participants |
| Tiotropium Bromide Via (Spiriva® Handihaler®) | Number of Participants With Adverse Events, Vital Signs, and Clinically Significant Abnormal ECG Values and Laboratory Tests | Clinical signicant abnormal vital signs | 0 Participants |
| Tiotropium Bromide Via (Spiriva® Handihaler®) | Number of Participants With Adverse Events, Vital Signs, and Clinically Significant Abnormal ECG Values and Laboratory Tests | Clinically significant abnormal ECG values Day 1 | 8 Participants |
| Tiotropium Bromide Via (Spiriva® Handihaler®) | Number of Participants With Adverse Events, Vital Signs, and Clinically Significant Abnormal ECG Values and Laboratory Tests | Clinically significant abnormal ECG values Day 7 | 8 Participants |
| Tiotropium Bromide Via (Spiriva® Handihaler®) | Number of Participants With Adverse Events, Vital Signs, and Clinically Significant Abnormal ECG Values and Laboratory Tests | Treatment emergent AEs | 12 Participants |
| Placebo | Number of Participants With Adverse Events, Vital Signs, and Clinically Significant Abnormal ECG Values and Laboratory Tests | Clinicall significant abnormal lab valuesday1-day7 | 3 Participants |
| Placebo | Number of Participants With Adverse Events, Vital Signs, and Clinically Significant Abnormal ECG Values and Laboratory Tests | Clinically significant abnormal ECG values Day 1 | 6 Participants |
| Placebo | Number of Participants With Adverse Events, Vital Signs, and Clinically Significant Abnormal ECG Values and Laboratory Tests | Clinical signicant abnormal vital signs | 1 Participants |
| Placebo | Number of Participants With Adverse Events, Vital Signs, and Clinically Significant Abnormal ECG Values and Laboratory Tests | Treatment emergent AEs | 25 Participants |
| Placebo | Number of Participants With Adverse Events, Vital Signs, and Clinically Significant Abnormal ECG Values and Laboratory Tests | Clinically significant abnormal ECG values Day 7 | 7 Participants |
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
Time frame: Day 1 and Day 7
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| EP-101 Via Nebulizer (eFlow®) 25 mcg | Peak FEV1 (Maximum FEV1 During the First 4 Hours Post-dose on Day 1 and Day 7) | Day 1 | 1.469 liters | Standard Deviation 0.5049 |
| EP-101 Via Nebulizer (eFlow®) 25 mcg | Peak FEV1 (Maximum FEV1 During the First 4 Hours Post-dose on Day 1 and Day 7) | Day 7 | 1.482 liters | Standard Deviation 0.4993 |
| EP-101 Via Nebulizer (eFlow®) 50 mcg | Peak FEV1 (Maximum FEV1 During the First 4 Hours Post-dose on Day 1 and Day 7) | Day 1 | 1.498 liters | Standard Deviation 0.4857 |
| EP-101 Via Nebulizer (eFlow®) 50 mcg | Peak FEV1 (Maximum FEV1 During the First 4 Hours Post-dose on Day 1 and Day 7) | Day 7 | 1.496 liters | Standard Deviation 0.4694 |
| EP-101 Via Nebulizer (eFlow®)100 mcg | Peak FEV1 (Maximum FEV1 During the First 4 Hours Post-dose on Day 1 and Day 7) | Day 1 | 1.443 liters | Standard Deviation 0.4431 |
| EP-101 Via Nebulizer (eFlow®)100 mcg | Peak FEV1 (Maximum FEV1 During the First 4 Hours Post-dose on Day 1 and Day 7) | Day 7 | 1.462 liters | Standard Deviation 0.43 |
| EP-101 Via Nebulizer (eFlow®) 200 mcg | Peak FEV1 (Maximum FEV1 During the First 4 Hours Post-dose on Day 1 and Day 7) | Day 1 | 1.455 liters | Standard Deviation 0.4355 |
| EP-101 Via Nebulizer (eFlow®) 200 mcg | Peak FEV1 (Maximum FEV1 During the First 4 Hours Post-dose on Day 1 and Day 7) | Day 7 | 1.453 liters | Standard Deviation 0.4476 |
| Ipratropium Bromide Inhalation Solution | Peak FEV1 (Maximum FEV1 During the First 4 Hours Post-dose on Day 1 and Day 7) | Day 1 | 1.601 liters | Standard Deviation 0.4665 |
| Ipratropium Bromide Inhalation Solution | Peak FEV1 (Maximum FEV1 During the First 4 Hours Post-dose on Day 1 and Day 7) | Day 7 | 1.594 liters | Standard Deviation 0.4943 |
| Tiotropium Bromide Via (Spiriva® Handihaler®) | Peak FEV1 (Maximum FEV1 During the First 4 Hours Post-dose on Day 1 and Day 7) | Day 1 | 1.434 liters | Standard Deviation 0.4774 |
| Tiotropium Bromide Via (Spiriva® Handihaler®) | Peak FEV1 (Maximum FEV1 During the First 4 Hours Post-dose on Day 1 and Day 7) | Day 7 | 1.475 liters | Standard Deviation 0.4556 |
| Placebo | Peak FEV1 (Maximum FEV1 During the First 4 Hours Post-dose on Day 1 and Day 7) | Day 1 | 1.356 liters | Standard Deviation 0.4471 |
| Placebo | Peak FEV1 (Maximum FEV1 During the First 4 Hours Post-dose on Day 1 and Day 7) | Day 7 | 1.348 liters | Standard Deviation 0.4465 |
Secondary
Rescue Medication Use
Mean number of puffs of daily rescue medication
Time frame: Day 1 through Day 7
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| EP-101 Via Nebulizer (eFlow®) 25 mcg | Rescue Medication Use | 1.34 average daily number of puffs | Standard Deviation 2.72 |
| EP-101 Via Nebulizer (eFlow®) 50 mcg | Rescue Medication Use | 1.11 average daily number of puffs | Standard Deviation 1.89 |
| EP-101 Via Nebulizer (eFlow®)100 mcg | Rescue Medication Use | 1.48 average daily number of puffs | Standard Deviation 2.43 |
| EP-101 Via Nebulizer (eFlow®) 200 mcg | Rescue Medication Use | 1.29 average daily number of puffs | Standard Deviation 2.7 |
| Ipratropium Bromide Inhalation Solution | Rescue Medication Use | 1.42 average daily number of puffs | Standard Deviation 2.91 |
| Tiotropium Bromide Via (Spiriva® Handihaler®) | Rescue Medication Use | 1.33 average daily number of puffs | Standard Deviation 3.01 |
| Placebo | Rescue Medication Use | 1.59 average daily number of puffs | Standard Deviation 2.16 |
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.
Time frame: Day 1 and Day 7
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| EP-101 Via Nebulizer (eFlow®) 25 mcg | Treatment Responders (Number of Subjects With Clinically Meaningful Change From Pre-dose in Trough FEV1 on Day 1 and Day 7) | Day 1 | 18 number of participants |
| EP-101 Via Nebulizer (eFlow®) 25 mcg | Treatment Responders (Number of Subjects With Clinically Meaningful Change From Pre-dose in Trough FEV1 on Day 1 and Day 7) | Day 7 | 29 number of participants |
| EP-101 Via Nebulizer (eFlow®) 50 mcg | Treatment Responders (Number of Subjects With Clinically Meaningful Change From Pre-dose in Trough FEV1 on Day 1 and Day 7) | Day 1 | 29 number of participants |
| EP-101 Via Nebulizer (eFlow®) 50 mcg | Treatment Responders (Number of Subjects With Clinically Meaningful Change From Pre-dose in Trough FEV1 on Day 1 and Day 7) | Day 7 | 30 number of participants |
| EP-101 Via Nebulizer (eFlow®)100 mcg | Treatment Responders (Number of Subjects With Clinically Meaningful Change From Pre-dose in Trough FEV1 on Day 1 and Day 7) | Day 1 | 24 number of participants |
| EP-101 Via Nebulizer (eFlow®)100 mcg | Treatment Responders (Number of Subjects With Clinically Meaningful Change From Pre-dose in Trough FEV1 on Day 1 and Day 7) | Day 7 | 34 number of participants |
| EP-101 Via Nebulizer (eFlow®) 200 mcg | Treatment Responders (Number of Subjects With Clinically Meaningful Change From Pre-dose in Trough FEV1 on Day 1 and Day 7) | Day 1 | 24 number of participants |
| EP-101 Via Nebulizer (eFlow®) 200 mcg | Treatment Responders (Number of Subjects With Clinically Meaningful Change From Pre-dose in Trough FEV1 on Day 1 and Day 7) | Day 7 | 37 number of participants |
| Ipratropium Bromide Inhalation Solution | Treatment Responders (Number of Subjects With Clinically Meaningful Change From Pre-dose in Trough FEV1 on Day 1 and Day 7) | Day 1 | 24 number of participants |
| Ipratropium Bromide Inhalation Solution | Treatment Responders (Number of Subjects With Clinically Meaningful Change From Pre-dose in Trough FEV1 on Day 1 and Day 7) | Day 7 | 27 number of participants |
| Tiotropium Bromide Via (Spiriva® Handihaler®) | Treatment Responders (Number of Subjects With Clinically Meaningful Change From Pre-dose in Trough FEV1 on Day 1 and Day 7) | Day 1 | 26 number of participants |
| Tiotropium Bromide Via (Spiriva® Handihaler®) | Treatment Responders (Number of Subjects With Clinically Meaningful Change From Pre-dose in Trough FEV1 on Day 1 and Day 7) | Day 7 | 37 number of participants |
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.
Time frame: Day 1 and Day 7
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| EP-101 Via Nebulizer (eFlow®) 25 mcg | Treatment Responders (Percentage of Subjects With Clinically Meaningful Change From Pre-dose in Trough FEV1 on Day 1 and Day 7) | Day 1 | 25.0 percentage of participants |
| EP-101 Via Nebulizer (eFlow®) 25 mcg | Treatment Responders (Percentage of Subjects With Clinically Meaningful Change From Pre-dose in Trough FEV1 on Day 1 and Day 7) | Day 7 | 40.3 percentage of participants |
| EP-101 Via Nebulizer (eFlow®) 50 mcg | Treatment Responders (Percentage of Subjects With Clinically Meaningful Change From Pre-dose in Trough FEV1 on Day 1 and Day 7) | Day 1 | 38.7 percentage of participants |
| EP-101 Via Nebulizer (eFlow®) 50 mcg | Treatment Responders (Percentage of Subjects With Clinically Meaningful Change From Pre-dose in Trough FEV1 on Day 1 and Day 7) | Day 7 | 40.0 percentage of participants |
| EP-101 Via Nebulizer (eFlow®)100 mcg | Treatment Responders (Percentage of Subjects With Clinically Meaningful Change From Pre-dose in Trough FEV1 on Day 1 and Day 7) | Day 1 | 32.0 percentage of participants |
| EP-101 Via Nebulizer (eFlow®)100 mcg | Treatment Responders (Percentage of Subjects With Clinically Meaningful Change From Pre-dose in Trough FEV1 on Day 1 and Day 7) | Day 7 | 46.6 percentage of participants |
| EP-101 Via Nebulizer (eFlow®) 200 mcg | Treatment Responders (Percentage of Subjects With Clinically Meaningful Change From Pre-dose in Trough FEV1 on Day 1 and Day 7) | Day 1 | 35.3 percentage of participants |
| EP-101 Via Nebulizer (eFlow®) 200 mcg | Treatment Responders (Percentage of Subjects With Clinically Meaningful Change From Pre-dose in Trough FEV1 on Day 1 and Day 7) | Day 7 | 51.4 percentage of participants |
| Ipratropium Bromide Inhalation Solution | Treatment Responders (Percentage of Subjects With Clinically Meaningful Change From Pre-dose in Trough FEV1 on Day 1 and Day 7) | Day 1 | 33.8 percentage of participants |
| Ipratropium Bromide Inhalation Solution | Treatment Responders (Percentage of Subjects With Clinically Meaningful Change From Pre-dose in Trough FEV1 on Day 1 and Day 7) | Day 7 | 37.5 percentage of participants |
| Tiotropium Bromide Via (Spiriva® Handihaler®) | Treatment Responders (Percentage of Subjects With Clinically Meaningful Change From Pre-dose in Trough FEV1 on Day 1 and Day 7) | Day 1 | 34.7 percentage of participants |
| Tiotropium Bromide Via (Spiriva® Handihaler®) | Treatment Responders (Percentage of Subjects With Clinically Meaningful Change From Pre-dose in Trough FEV1 on Day 1 and Day 7) | Day 7 | 48.7 percentage of participants |