Chronic Obstructive Pulmonary Disease
Conditions
Keywords
Chronic Obstructive Pulmonary Disease, COPD, Emphysema, Chronic bronchitis
Brief summary
The study assessed the safety and ability of an orally inhaled medicine \[i.e., Glycopyrrolate Inhalation Solution = GIS\] to improve airflow in the lungs when delivered using an eFlow nebulizer in 42 patients with Chronic Obstructive Pulmonary Disease (COPD). Each patient randomly received several, single doses of GIS, or placebo, separated by approximately 1 to 2 weeks. After the dose was given, lung airflow was measured over 24 hours and blood was collected to measure how much GIS was in the bloodstream. The study was conducted to find the once-a- day GIS dose that produced the highest improvement in lung airflow using the eFlow nebulizer.
Interventions
DRUGGlycopyrrolate Inhalation Solution12.5μg
Glycopyrrolate Inhalation Solution12.5μg via eFlow, once daily
DRUGGlycopyrrolate Inhalation Solution 50μg
Glycopyrrolate Inhalation Solution 50μg via eFlow, once daily
DRUGGlycopyrrolate Inhalation Solution 100μg
Glycopyrrolate Inhalation Solution 100μg via eFlow, once daily
DRUGGlycopyrrolate Inhalation Solution 200μg
Glycopyrrolate Inhalation Solution 200μg via eFlow, once daily
DRUGGlycopyrrolate Inhalation Solution 400μg
Glycopyrrolate Inhalation Solution 400μg via eFlow, once daily
DRUGPlacebo 0.5mL
Placebo 0.5mL via eFlow, once daily
Sponsors
Sunovion Respiratory Development Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Age
40 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Male and female patients aged 40 through 75 years, inclusive 2. A clinical diagnosis of COPD according to the GOLD guidelines 3. Current smokers or ex-smokers with at least 10 pack-year smoking history (e.g., at least 1 pack/day for 10 4. Post-bronchodilator FEV1 30-70% of predicted normal at the Screening Visit 5. Post-bronchodilator FEV1/FVC ratio \< 0.70 at the Screening Visit 6. Improvement in FEV1 \>12% and 150 mL following inhalation of ipratropium bromide at the Screening Visit 7. Ability to perform reproducible spirometry according to the ATS/ERS guidelines 8. Willing to stay at the study site for approximately 30 hours on each treatment visit 9. Willing and able to provide written informed consent
Exclusion criteria
1. Females who are pregnant or lactating at the Screening Visit, or if of childbearing potential not using one of the following acceptable means of birth control throughout the study: * Abstinence * Post-menopausal for at least two years * Surgically sterile (i.e., tubal ligation, hysterectomy) * Oral contraceptives (taken for at least one month prior to the Screening Visit) * Approved implantable or injectable contraceptives (e.g., Norplant®, Depo-Provera® or equivalent) * Barrier methods (e.g., condoms with spermicide) * Intrauterine device (i.e., IUD) * Vasectomy of male partner * Non-heterosexual life style 2. Current evidence or recent history of any clinically significant disease (other than COPD) or abnormality in the opinion of the Investigator that would put the subject at risk or which would compromise the quality of the study data; including but not limited to cardiovascular disease, myocardial infarction, cardiac failure, uncontrolled hypertension, life-threatening arrhythmias, uncontrolled diabetes, neurologic or neuromuscular disease, liver disease, gastrointestinal disease or electrolyte abnormalities 3. Recent history of hospitalization due to an exacerbation of airway disease within 3 months or need for increased treatments for COPD within 6 weeks prior to the Screening Visit 4. Primary diagnosis of asthma 5. Prior lung volume reduction surgery or history of chest/lung irradiation 6. Regular use of daily oxygen therapy 7. Use of systemic (eg, intramuscular or intravenous) steroids within 3 months prior to the Screening Visit 8. Respiratory tract infection within 6 weeks prior to the Screening Visit 9. History of tuberculosis, bronchiectasis or other non- specific pulmonary disease 10. History of urinary retention or bladder neck obstruction type symptoms 11. History of narrow-angle glaucoma 12. Clinically significant abnormal ECG 13. Positive Hepatitis B surface antigen or positive Hepatitis C antibody 14. Positive screening test for HIV antibodies 15. Current or recent history (previous 12 months) of excessive use or abuse of alcohol 16. Current evidence or history of abusing legal drugs or use of illegal drugs or substances 17. Donation of 450 mL of blood within 8 weeks of the Screening Visit 18. History of hypersensitivity or intolerance to aerosol medications 19. Participation in another investigational drug study was received within 30 days prior to the Screening Visit
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Trough FEV1 (Change From Baseline) | 24hr post dose | Spirometry measurements were conducted in accordance with the current ATS/ERS 2005 guidelines. Trough FEV1 was defined as the mean of FEV1 values obtained at 23 hours 30 minutes and 24 hours post-dose of each Treatment Visit. |
| Standardized FEV1AUC0-12 Area Under the FEV1 Curve From 0 to 12 Hours Post-dose ( Actual and Change From Baseline). | 0-12h post dose | Spirometry measurements were conducted in accordance with the current ATS/ERS 2005 guidelines.. The standardized actual FEV1 AUC(0-12) was calculated using the trapezoidal rule divided by the actual hours from the first FEV1 to the last FEV1 in the interval. Standardized change from baseline FEV1 AUC(0-12) was also calculated similarly, using the change from pre-dose FEV1. |
| Standardized FEV1AUC12-24 Area Under the FEV1 Curve From 12 to 24 Hours Post- Dose (Actual and Change From Baseline). | 12-24h post dose | Spirometry measurements were conducted in accordance with the current ATS/ERS 2005 guidelines. The standardized actual FEV1 AUC(12-24) was calculated using the trapezoidal rule divided by the actual hours from the first FEV1 to the last FEV1 in the interval. Standardized change from baseline FEV1 AUC(12-24) was also calculated similarly, using the change from pre-dose FEV1. |
| Standardized FEV1 AUC0-24 Area Under the FEV1 Curve From 0 to 24 Hours Post-dose (Actual and Change Baseline) | 0 to 24h | Spirometry measurements were conducted in accordance with the current ATS/ERS 2005 guidelines. . The standardized actual FEV1 AUC(0-24) was calculated using the trapezoidal rule divided by the actual hours from the first FEV1 to the last FEV1 in the interval. Standardized change from baseline FEV1 AUC(0-24) was also calculated similarly, using the change from pre-dose FEV1. |
| Peak FEV1 (Change From Baseline and Percent Change) | 0-4h post dose | spirometry measurements were conducted in accordance with the current ATS/ERS 2005 guidelines. . The peak FEV1 was defined as the highest post-dose FEV1 value within 4 hrs after the dose. Percent change from baseline was calculated as 100 times the difference of peak FEV1 minus baseline FEV1 divided by baseline FEV1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Who Died, Number of Subjects With Treatment Emergent SAEs, Number of Subjects Who Discontinued Due to AE | Day 69 (includes dosing Day 1, washout Day 12, safety follow up Day 69) | AE's are defined as existing conditions which worsen or events which occur during the course of the clinical trial after treatment |
| Number of Subjects With Clinically Significant Abnormal Vital Signs Reported During the Study | 0-24 h | Vital signs were measured at screening and at each Treatment Visit pre-dose (within 30 minutes prior to dose); post-dose at 30 minutes and 1, 2, 4, 8, 12 and 24 hours; and then at the post study assessment. |
| Cmax; Maximum Observed Plasma Concentration | 0 to 12 hour | Pk parameters are calculated from glycopyrrolate plasma concentration analysed from serial blood samples collected between 0 and 12 hr |
| Number of Subjects With Clinically Significant ECG Parameters Reported During the Study | 0 to 24h | ECGs were recorded at screening and at each study treatment visit pre-dose (within 30 minutes prior to dose); post-dose at 30 minutes and 1, 2, 4, 8, 12 and 24 hours; and then at the post study assessment. |
| Percentage of Subjects With Treatment Emergent AEs | Day 69 (includes dosing Day 1, washout Day 12, safety follow up Day 69) | AE's are defined as existing conditions which worsen or events which occur during the course of the clinical trial after treatment |
| Number of Clinically Significant Abnormal Laboratory Results Reported During the Study | Day -14, Day 69 | Clinical safety lab parameters were collected at screening and at the post study assessment. Any laboratory values that were out of range of normal reference values were evaluated by the Investigators. |
| Tmax; Time to Maximum Observed Plasma Concentration | 0 to 12 hours | Pk parameters are calculated from glycopyrrolate plasma concentration analysed from serial blood samples collected between 0 and 12 hr |
| t1/2; Plasma Half-life | 0 to 12 hour | Pk parameters are calculated from glycopyrrolate plasma concentration analysed from serial blood samples collected between 0 and 12 hr |
| AUC0-t; Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Measurable Drug Concentration. | 0 to 12 hour | Pk parameters are calculated from glycopyrrolate plasma concentration analysed from serial blood samples collected between 0 and 12 hr |
| AUC0-inf Area Under the Plasma Concentration-time Curve From Time Zero to Infinity | 0 to 12 hour | Pk parameters are calculated from glycopyrrolate plasma concentration analysed from serial blood samples collected between 0 and 12 hr |
Participant flow
Pre-assignment details
All enrolled subjects were randomized. all randomized subjects received at least one dose of study medication
Participants by arm
| Arm | Count |
|---|---|
| Total Participants Intent to treat population same as safety population -not full analysis set | 42 |
| Total | 42 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Washout Period 1 | Adverse Event | 0 | 2 | 0 | 0 | 0 | 0 |
| Washout Period 1 | Protocol Violation | 0 | 0 | 0 | 0 | 0 | 1 |
| Washout Period 2 | Adverse Event | 0 | 1 | 0 | 0 | 0 | 0 |
| Washout Period 2 | personal reasons | 0 | 0 | 0 | 1 | 0 | 0 |
| Washout Period 4 | Adverse Event | 1 | 0 | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Total Participants |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 13 Participants |
| Age, Categorical Between 18 and 65 years | 29 Participants |
| Age, Continuous | 62.0 years STANDARD_DEVIATION 6.99 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 42 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 1 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 | 41 Participants |
| Region of Enrollment United Kingdom | 42 Participants |
| Sex: Female, Male Female | 15 Participants |
| Sex: Female, Male Male | 27 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 |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 13 / 39 | 9 / 38 | 10 / 37 | 10 / 37 | 10 / 37 | 10 / 37 |
| serious Total, serious adverse events | 0 / 39 | 0 / 38 | 1 / 37 | 0 / 37 | 0 / 37 | 0 / 37 |
Outcome results
Primary
Peak FEV1 (Change From Baseline and Percent Change)
spirometry measurements were conducted in accordance with the current ATS/ERS 2005 guidelines. . The peak FEV1 was defined as the highest post-dose FEV1 value within 4 hrs after the dose. Percent change from baseline was calculated as 100 times the difference of peak FEV1 minus baseline FEV1 divided by baseline FEV1.
Time frame: 0-4h post dose
Population: all subjects who received at least one dose of study medication and have at least one post baseline efficacy measurement were included in the efficacy population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Glycopyrrolate Inhalation Solution12.5μg | Peak FEV1 (Change From Baseline and Percent Change) | Change from baseline | 0.165 liters | Standard Deviation 0.113 |
| Glycopyrrolate Inhalation Solution12.5μg | Peak FEV1 (Change From Baseline and Percent Change) | percent change from baseline | 15.30 liters | Standard Deviation 11.37 |
| Glycopyrrolate Inhalation Solution 50μg | Peak FEV1 (Change From Baseline and Percent Change) | Change from baseline | 0.229 liters | Standard Deviation 0.113 |
| Glycopyrrolate Inhalation Solution 50μg | Peak FEV1 (Change From Baseline and Percent Change) | percent change from baseline | 21.05 liters | Standard Deviation 11.87 |
| Glycopyrrolate Inhalation Solution 100μg | Peak FEV1 (Change From Baseline and Percent Change) | Change from baseline | 0.260 liters | Standard Deviation 0.151 |
| Glycopyrrolate Inhalation Solution 100μg | Peak FEV1 (Change From Baseline and Percent Change) | percent change from baseline | 24.14 liters | Standard Deviation 20.69 |
| Glycopyrrolate Inhalation Solution 200μg | Peak FEV1 (Change From Baseline and Percent Change) | percent change from baseline | 26.73 liters | Standard Deviation 12.56 |
| Glycopyrrolate Inhalation Solution 200μg | Peak FEV1 (Change From Baseline and Percent Change) | Change from baseline | 0.292 liters | Standard Deviation 0.12 |
| Glycopyrrolate Inhalation Solution 400μg | Peak FEV1 (Change From Baseline and Percent Change) | Change from baseline | 0.272 liters | Standard Deviation 0.125 |
| Glycopyrrolate Inhalation Solution 400μg | Peak FEV1 (Change From Baseline and Percent Change) | percent change from baseline | 25.44 liters | Standard Deviation 15.1 |
| Placebo 0.5mL | Peak FEV1 (Change From Baseline and Percent Change) | Change from baseline | 0.061 liters | Standard Deviation 0.102 |
| Placebo 0.5mL | Peak FEV1 (Change From Baseline and Percent Change) | percent change from baseline | 5.24 liters | Standard Deviation 8275 |
Primary
Standardized FEV1AUC0-12 Area Under the FEV1 Curve From 0 to 12 Hours Post-dose ( Actual and Change From Baseline).
Spirometry measurements were conducted in accordance with the current ATS/ERS 2005 guidelines.. The standardized actual FEV1 AUC(0-12) was calculated using the trapezoidal rule divided by the actual hours from the first FEV1 to the last FEV1 in the interval. Standardized change from baseline FEV1 AUC(0-12) was also calculated similarly, using the change from pre-dose FEV1.
Time frame: 0-12h post dose
Population: All subjects who received at least one dose of study medication and had at least one postbaseline efficacy measurement (FEV1) were included in the intent to treat analysis
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Glycopyrrolate Inhalation Solution12.5μg | Standardized FEV1AUC0-12 Area Under the FEV1 Curve From 0 to 12 Hours Post-dose ( Actual and Change From Baseline). | change from baseline standardized FEV1 AUC0_12 | 0.055 liters | Standard Deviation 0.113 |
| Glycopyrrolate Inhalation Solution12.5μg | Standardized FEV1AUC0-12 Area Under the FEV1 Curve From 0 to 12 Hours Post-dose ( Actual and Change From Baseline). | actual standardized FEV1 AUC0_12 | 1.259 liters | Standard Deviation 0.409 |
| Glycopyrrolate Inhalation Solution 50μg | Standardized FEV1AUC0-12 Area Under the FEV1 Curve From 0 to 12 Hours Post-dose ( Actual and Change From Baseline). | change from baseline standardized FEV1 AUC0_12 | 0.126 liters | Standard Deviation 0.112 |
| Glycopyrrolate Inhalation Solution 50μg | Standardized FEV1AUC0-12 Area Under the FEV1 Curve From 0 to 12 Hours Post-dose ( Actual and Change From Baseline). | actual standardized FEV1 AUC0_12 | 1.311 liters | Standard Deviation 0.422 |
| Glycopyrrolate Inhalation Solution 100μg | Standardized FEV1AUC0-12 Area Under the FEV1 Curve From 0 to 12 Hours Post-dose ( Actual and Change From Baseline). | change from baseline standardized FEV1 AUC0_12 | 0.136 liters | Standard Deviation 0.134 |
| Glycopyrrolate Inhalation Solution 100μg | Standardized FEV1AUC0-12 Area Under the FEV1 Curve From 0 to 12 Hours Post-dose ( Actual and Change From Baseline). | actual standardized FEV1 AUC0_12 | 1.335 liters | Standard Deviation 0.394 |
| Glycopyrrolate Inhalation Solution 200μg | Standardized FEV1AUC0-12 Area Under the FEV1 Curve From 0 to 12 Hours Post-dose ( Actual and Change From Baseline). | change from baseline standardized FEV1 AUC0_12 | 0.184 liters | Standard Deviation 0.134 |
| Glycopyrrolate Inhalation Solution 200μg | Standardized FEV1AUC0-12 Area Under the FEV1 Curve From 0 to 12 Hours Post-dose ( Actual and Change From Baseline). | actual standardized FEV1 AUC0_12 | 1.374 liters | Standard Deviation 0.391 |
| Glycopyrrolate Inhalation Solution 400μg | Standardized FEV1AUC0-12 Area Under the FEV1 Curve From 0 to 12 Hours Post-dose ( Actual and Change From Baseline). | actual standardized FEV1 AUC0_12 | 1.390 liters | Standard Deviation 0.423 |
| Glycopyrrolate Inhalation Solution 400μg | Standardized FEV1AUC0-12 Area Under the FEV1 Curve From 0 to 12 Hours Post-dose ( Actual and Change From Baseline). | change from baseline standardized FEV1 AUC0_12 | 0.170 liters | Standard Deviation 0.11 |
| Placebo 0.5mL | Standardized FEV1AUC0-12 Area Under the FEV1 Curve From 0 to 12 Hours Post-dose ( Actual and Change From Baseline). | actual standardized FEV1 AUC0_12 | 1.180 liters | Standard Deviation 0.427 |
| Placebo 0.5mL | Standardized FEV1AUC0-12 Area Under the FEV1 Curve From 0 to 12 Hours Post-dose ( Actual and Change From Baseline). | change from baseline standardized FEV1 AUC0_12 | -0.024 liters | Standard Deviation 0.095 |
Comparison: An analysis of covariance was used with change from baseline in standardized FEV1 AUC0\_12 as the response, with factors for center, treatment, period, sequence, baseline FEV1 as a covariate and a random effect for subject nested within sequence.p-value: <0.000195% CI: [0.05, 0.123]least squares mean
Comparison: An analysis of covariance was used with change from baseline in standardized FEV1 AUC0\_12 as the response, with factors for center, treatment, period, sequence, baseline FEV1 as a covariate and a random effect for subject nested within sequence.p-value: <0.000195% CI: [0.114, 0.187]least squares mean
Comparison: An analysis of covariance was used with change from baseline in standardized FEV1 AUC0\_12 as the response, with factors for center, treatment, period, sequence, baseline FEV1 as a covariate and a random effect for subject nested within sequence.p-value: <0.000195% CI: [0.12, 0.193]least squares mean
Comparison: An analysis of covariance was used with change from baseline in standardized FEV1 AUC0\_12 as the response, with factors for center, treatment, period, sequence, baseline FEV1 as a covariate and a random effect for subject nested within sequence.p-value: <0.000195% CI: [0.165, 0.239]least squares mean
Comparison: An analysis of covariance was used with change from baseline in standardized FEV1 AUC0\_12 as the response, with factors for center, treatment, period, sequence, baseline FEV1 as a covariate and a random effect for subject nested within sequence.p-value: <0.000195% CI: [0.162, 0.235]least squares mean
Primary
Standardized FEV1 AUC0-24 Area Under the FEV1 Curve From 0 to 24 Hours Post-dose (Actual and Change Baseline)
Spirometry measurements were conducted in accordance with the current ATS/ERS 2005 guidelines. . The standardized actual FEV1 AUC(0-24) was calculated using the trapezoidal rule divided by the actual hours from the first FEV1 to the last FEV1 in the interval. Standardized change from baseline FEV1 AUC(0-24) was also calculated similarly, using the change from pre-dose FEV1.
Time frame: 0 to 24h
Population: all subjects who received at least one dose of study medication and had at least one postbaseline efficacy measurement (FEV1) were included in the intent to treat analysis
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Glycopyrrolate Inhalation Solution12.5μg | Standardized FEV1 AUC0-24 Area Under the FEV1 Curve From 0 to 24 Hours Post-dose (Actual and Change Baseline) | Actual standardized FEV1 AUC0_12 | 1.212 liters | Standard Deviation 0.391 |
| Glycopyrrolate Inhalation Solution12.5μg | Standardized FEV1 AUC0-24 Area Under the FEV1 Curve From 0 to 24 Hours Post-dose (Actual and Change Baseline) | change from baseline standardized FEV1 AUC0_12 | 0.009 liters | Standard Deviation 0.114 |
| Glycopyrrolate Inhalation Solution 50μg | Standardized FEV1 AUC0-24 Area Under the FEV1 Curve From 0 to 24 Hours Post-dose (Actual and Change Baseline) | Actual standardized FEV1 AUC0_12 | 1.257 liters | Standard Deviation 0.411 |
| Glycopyrrolate Inhalation Solution 50μg | Standardized FEV1 AUC0-24 Area Under the FEV1 Curve From 0 to 24 Hours Post-dose (Actual and Change Baseline) | change from baseline standardized FEV1 AUC0_12 | 0.072 liters | Standard Deviation 0.115 |
| Glycopyrrolate Inhalation Solution 100μg | Standardized FEV1 AUC0-24 Area Under the FEV1 Curve From 0 to 24 Hours Post-dose (Actual and Change Baseline) | Actual standardized FEV1 AUC0_12 | 1.281 liters | Standard Deviation 0.379 |
| Glycopyrrolate Inhalation Solution 100μg | Standardized FEV1 AUC0-24 Area Under the FEV1 Curve From 0 to 24 Hours Post-dose (Actual and Change Baseline) | change from baseline standardized FEV1 AUC0_12 | 0.082 liters | Standard Deviation 0.128 |
| Glycopyrrolate Inhalation Solution 200μg | Standardized FEV1 AUC0-24 Area Under the FEV1 Curve From 0 to 24 Hours Post-dose (Actual and Change Baseline) | Actual standardized FEV1 AUC0_12 | 1.313 liters | Standard Deviation 0.364 |
| Glycopyrrolate Inhalation Solution 200μg | Standardized FEV1 AUC0-24 Area Under the FEV1 Curve From 0 to 24 Hours Post-dose (Actual and Change Baseline) | change from baseline standardized FEV1 AUC0_12 | 0.123 liters | Standard Deviation 0.146 |
| Glycopyrrolate Inhalation Solution 400μg | Standardized FEV1 AUC0-24 Area Under the FEV1 Curve From 0 to 24 Hours Post-dose (Actual and Change Baseline) | Actual standardized FEV1 AUC0_12 | 1.325 liters | Standard Deviation 0.407 |
| Glycopyrrolate Inhalation Solution 400μg | Standardized FEV1 AUC0-24 Area Under the FEV1 Curve From 0 to 24 Hours Post-dose (Actual and Change Baseline) | change from baseline standardized FEV1 AUC0_12 | 0.105 liters | Standard Deviation 0.113 |
| Placebo 0.5mL | Standardized FEV1 AUC0-24 Area Under the FEV1 Curve From 0 to 24 Hours Post-dose (Actual and Change Baseline) | Actual standardized FEV1 AUC0_12 | 1.151 liters | Standard Deviation 0.408 |
| Placebo 0.5mL | Standardized FEV1 AUC0-24 Area Under the FEV1 Curve From 0 to 24 Hours Post-dose (Actual and Change Baseline) | change from baseline standardized FEV1 AUC0_12 | -0.053 liters | Standard Deviation 0.102 |
Primary
Standardized FEV1AUC12-24 Area Under the FEV1 Curve From 12 to 24 Hours Post- Dose (Actual and Change From Baseline).
Spirometry measurements were conducted in accordance with the current ATS/ERS 2005 guidelines. The standardized actual FEV1 AUC(12-24) was calculated using the trapezoidal rule divided by the actual hours from the first FEV1 to the last FEV1 in the interval. Standardized change from baseline FEV1 AUC(12-24) was also calculated similarly, using the change from pre-dose FEV1.
Time frame: 12-24h post dose
Population: All subjects who received at least one dose of study medication and had at least one postbaseline efficacy measurement (FEV1) were included in the intent to treat analysis
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Glycopyrrolate Inhalation Solution12.5μg | Standardized FEV1AUC12-24 Area Under the FEV1 Curve From 12 to 24 Hours Post- Dose (Actual and Change From Baseline). | change from baseline standardized FEV1 AUC0_12 | -0.038 liters | Standard Deviation 0.132 |
| Glycopyrrolate Inhalation Solution12.5μg | Standardized FEV1AUC12-24 Area Under the FEV1 Curve From 12 to 24 Hours Post- Dose (Actual and Change From Baseline). | acutal standardized FEV1 AUC0_12 | 1.165 liters | Standard Deviation 0.377 |
| Glycopyrrolate Inhalation Solution 50μg | Standardized FEV1AUC12-24 Area Under the FEV1 Curve From 12 to 24 Hours Post- Dose (Actual and Change From Baseline). | acutal standardized FEV1 AUC0_12 | 1.203 liters | Standard Deviation 0.404 |
| Glycopyrrolate Inhalation Solution 50μg | Standardized FEV1AUC12-24 Area Under the FEV1 Curve From 12 to 24 Hours Post- Dose (Actual and Change From Baseline). | change from baseline standardized FEV1 AUC0_12 | 0.018 liters | Standard Deviation 0.135 |
| Glycopyrrolate Inhalation Solution 100μg | Standardized FEV1AUC12-24 Area Under the FEV1 Curve From 12 to 24 Hours Post- Dose (Actual and Change From Baseline). | acutal standardized FEV1 AUC0_12 | 1.227 liters | Standard Deviation 0.369 |
| Glycopyrrolate Inhalation Solution 100μg | Standardized FEV1AUC12-24 Area Under the FEV1 Curve From 12 to 24 Hours Post- Dose (Actual and Change From Baseline). | change from baseline standardized FEV1 AUC0_12 | 0.028 liters | Standard Deviation 0.138 |
| Glycopyrrolate Inhalation Solution 200μg | Standardized FEV1AUC12-24 Area Under the FEV1 Curve From 12 to 24 Hours Post- Dose (Actual and Change From Baseline). | acutal standardized FEV1 AUC0_12 | 1.253 liters | Standard Deviation 0.346 |
| Glycopyrrolate Inhalation Solution 200μg | Standardized FEV1AUC12-24 Area Under the FEV1 Curve From 12 to 24 Hours Post- Dose (Actual and Change From Baseline). | change from baseline standardized FEV1 AUC0_12 | 0.063 liters | Standard Deviation 0.178 |
| Glycopyrrolate Inhalation Solution 400μg | Standardized FEV1AUC12-24 Area Under the FEV1 Curve From 12 to 24 Hours Post- Dose (Actual and Change From Baseline). | acutal standardized FEV1 AUC0_12 | 1.259 liters | Standard Deviation 0.396 |
| Glycopyrrolate Inhalation Solution 400μg | Standardized FEV1AUC12-24 Area Under the FEV1 Curve From 12 to 24 Hours Post- Dose (Actual and Change From Baseline). | change from baseline standardized FEV1 AUC0_12 | 0.039 liters | Standard Deviation 0.135 |
| Placebo 0.5mL | Standardized FEV1AUC12-24 Area Under the FEV1 Curve From 12 to 24 Hours Post- Dose (Actual and Change From Baseline). | acutal standardized FEV1 AUC0_12 | 1.123 liters | Standard Deviation 0.392 |
| Placebo 0.5mL | Standardized FEV1AUC12-24 Area Under the FEV1 Curve From 12 to 24 Hours Post- Dose (Actual and Change From Baseline). | change from baseline standardized FEV1 AUC0_12 | -0.082 liters | Standard Deviation 0.12 |
Comparison: An analysis of covariance was used with change from baseline in standardized FEV1 AUC12\_24 as the response, with factors for center, treatment, period, sequence, baseline FEV1 as a covariate and a random effect for subject nested within sequence.p-value: 0.002895% CI: [0.021, 0.095]least squares mean
Comparison: An analysis of covariance was used with change from baseline in standardized FEV1 AUC12\_24 as the response, with factors for center, treatment, period, sequence, baseline FEV1 as a covariate and a random effect for subject nested within sequence.p-value: <0.000195% CI: [0.063, 0.137]least squares mena
Comparison: An analysis of covariance was used with change from baseline in standardized FEV1 AUC12\_24 as the response, with factors for center, treatment, period, sequence, baseline FEV1 as a covariate and a random effect for subject nested within sequence.p-value: <0.000195% CI: [0.068, 0.142]least squares mean
Comparison: An analysis of covariance was used with change from baseline in standardized FEV1 AUC12\_24 as the response, with factors for center, treatment, period, sequence, baseline FEV1 as a covariate and a random effect for subject nested within sequence.p-value: <0.000195% CI: [0.098, 0.173]least squares mean
Comparison: An analysis of covariance was used with change from baseline in standardized FEV1 AUC12\_24 as the response, with factors for center, treatment, period, sequence, baseline FEV1 as a covariate and a random effect for subject nested within sequence.p-value: <0.000195% CI: [0.091, 0.166]least squares mean
Primary
Trough FEV1 (Change From Baseline)
Spirometry measurements were conducted in accordance with the current ATS/ERS 2005 guidelines. Trough FEV1 was defined as the mean of FEV1 values obtained at 23 hours 30 minutes and 24 hours post-dose of each Treatment Visit.
Time frame: 24hr post dose
Population: All subjects who received at least one dose of study medication and had at least one postbaseline efficacy measurement (FEV1) were included in the intent-to-treat analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Glycopyrrolate Inhalation Solution12.5μg | Trough FEV1 (Change From Baseline) | -0.093 liters | Standard Deviation 0.1189 |
| Glycopyrrolate Inhalation Solution 50μg | Trough FEV1 (Change From Baseline) | 0.0114 liters | Standard Deviation 0.1308 |
| Glycopyrrolate Inhalation Solution 100μg | Trough FEV1 (Change From Baseline) | 0.0447 liters | Standard Deviation 0.1548 |
| Glycopyrrolate Inhalation Solution 200μg | Trough FEV1 (Change From Baseline) | 0.0542 liters | Standard Deviation 0.1779 |
| Glycopyrrolate Inhalation Solution 400μg | Trough FEV1 (Change From Baseline) | 0.0292 liters | Standard Deviation 0.1468 |
| Placebo 0.5mL | Trough FEV1 (Change From Baseline) | -0.0612 liters | Standard Deviation 0.1233 |
Comparison: An analysis of covariance was used with change from baseline in trough FEV1 as the response, with factors for center, treatment, period, sequence, baseline FEV1 as a covariate and a random effect for subject nested within sequence.~A sample size of 34 subjects (42 with dropouts) provides 80% power to detect a 0.14L difference in mean change trough FEV1 between 2 groups at an alpha of 0.05 using a 2-tailed t-test and assuming a common standard deviation for change in trough FEV1 of 0.2.p-value: 0.125795% CI: [-0.009, 0.075]least squares mean
Comparison: An analysis of covariance was used with change from baseline in trough FEV1 as the response, with factors for center, treatment, period, sequence, baseline FEV1 as a covariate and a random effect for subject nested within sequence.~A sample size of 34 subjects (42 with dropouts) provides 80% power to detect a 0.14L difference in mean change trough FEV1 between 2 groups at an alpha of 0.05 using a 2-tailed t-test and assuming a common standard deviation for change in trough FEV1 of 0.2.p-value: 0.000895% CI: [0.03, 0.113]least squares mean
Comparison: An analysis of covariance was used with change from baseline in trough FEV1 as the response, with factors for center, treatment, period, sequence, baseline FEV1 as a covariate and a random effect for subject nested within sequence.~A sample size of 34 subjects (42 with dropouts) provides 80% power to detect a 0.14L difference in mean change trough FEV1 between 2 groups at an alpha of 0.05 using a 2-tailed t-test and assuming a common standard deviation for change in trough FEV1 of 0.2.p-value: <0.000195% CI: [0.061, 0.144]least squares mean
Comparison: An analysis of covariance was used with change from baseline in trough FEV1 as the response, with factors for center, treatment, period, sequence, baseline FEV1 as a covariate and a random effect for subject nested within sequence.~A sample size of 34 subjects (42 with dropouts) provides 80% power to detect a 0.14L difference in mean change trough FEV1 between 2 groups at an alpha of 0.05 using a 2-tailed t-test and assuming a common standard deviation for change in trough FEV1 of 0.2.p-value: <0.000195% CI: [0.066, 0.15]least squares mean
Comparison: An analysis of covariance was used with change from baseline in trough FEV1 as the response, with factors for center, treatment, period, sequence, baseline FEV1 as a covariate and a random effect for subject nested within sequence.~A sample size of 34 subjects (42 with dropouts) provides 80% power to detect a 0.14L difference in mean change trough FEV1 between 2 groups at an alpha of 0.05 using a 2-tailed t-test and assuming a common standard deviation for change in trough FEV1 of 0.2.p-value: <0.000195% CI: [0.056, 0.14]least squares mean
Secondary
AUC0-inf Area Under the Plasma Concentration-time Curve From Time Zero to Infinity
Pk parameters are calculated from glycopyrrolate plasma concentration analysed from serial blood samples collected between 0 and 12 hr
Time frame: 0 to 12 hour
Population: All subjects who received at least one dose of EP-101 and who have sufficient blood samples taken to obtain a plasma concentration by time profile and have no major protocol violations were included in the PK analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Glycopyrrolate Inhalation Solution 50μg | AUC0-inf Area Under the Plasma Concentration-time Curve From Time Zero to Infinity | 246.84 pg.h/ml | Geometric Coefficient of Variation 37.49 |
| Glycopyrrolate Inhalation Solution 100μg | AUC0-inf Area Under the Plasma Concentration-time Curve From Time Zero to Infinity | 634.65 pg.h/ml | Geometric Coefficient of Variation 34.28 |
| Glycopyrrolate Inhalation Solution 200μg | AUC0-inf Area Under the Plasma Concentration-time Curve From Time Zero to Infinity | 772.59 pg.h/ml | Geometric Coefficient of Variation 26.3 |
| Glycopyrrolate Inhalation Solution 400μg | AUC0-inf Area Under the Plasma Concentration-time Curve From Time Zero to Infinity | 1367.76 pg.h/ml | Geometric Coefficient of Variation 76.7 |
Secondary
AUC0-t; Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Measurable Drug Concentration.
Pk parameters are calculated from glycopyrrolate plasma concentration analysed from serial blood samples collected between 0 and 12 hr
Time frame: 0 to 12 hour
Population: All subjects who received at least one dose of EP-101 and who have sufficient blood samples taken to obtain a plasma concentration by time profile and have no major protocol violations were included in the PK analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Glycopyrrolate Inhalation Solution12.5μg | AUC0-t; Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Measurable Drug Concentration. | 135.87 pg.h/ml | Geometric Coefficient of Variation 209.27 |
| Glycopyrrolate Inhalation Solution 50μg | AUC0-t; Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Measurable Drug Concentration. | 67.18 pg.h/ml | Geometric Coefficient of Variation 143.22 |
| Glycopyrrolate Inhalation Solution 100μg | AUC0-t; Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Measurable Drug Concentration. | 237.80 pg.h/ml | Geometric Coefficient of Variation 98.45 |
| Glycopyrrolate Inhalation Solution 200μg | AUC0-t; Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Measurable Drug Concentration. | 677.24 pg.h/ml | Geometric Coefficient of Variation 66.34 |
| Glycopyrrolate Inhalation Solution 400μg | AUC0-t; Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Measurable Drug Concentration. | 1481.36 pg.h/ml | Geometric Coefficient of Variation 82.17 |
Secondary
Cmax; Maximum Observed Plasma Concentration
Pk parameters are calculated from glycopyrrolate plasma concentration analysed from serial blood samples collected between 0 and 12 hr
Time frame: 0 to 12 hour
Population: All subjects who received at least one dose of EP-101 and who have sufficient blood samples taken to obtain a plasma concentration by time profile and have no major protocol violations were included in the PK analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Glycopyrrolate Inhalation Solution12.5μg | Cmax; Maximum Observed Plasma Concentration | 59.25 pg/mL | Geometric Coefficient of Variation 78.49 |
| Glycopyrrolate Inhalation Solution 50μg | Cmax; Maximum Observed Plasma Concentration | 74.48 pg/mL | Geometric Coefficient of Variation 62.24 |
| Glycopyrrolate Inhalation Solution 100μg | Cmax; Maximum Observed Plasma Concentration | 144.58 pg/mL | Geometric Coefficient of Variation 52.53 |
| Glycopyrrolate Inhalation Solution 200μg | Cmax; Maximum Observed Plasma Concentration | 316.05 pg/mL | Geometric Coefficient of Variation 48.35 |
| Glycopyrrolate Inhalation Solution 400μg | Cmax; Maximum Observed Plasma Concentration | 504.93 pg/mL | Geometric Coefficient of Variation 55.67 |
Secondary
Number of Clinically Significant Abnormal Laboratory Results Reported During the Study
Clinical safety lab parameters were collected at screening and at the post study assessment. Any laboratory values that were out of range of normal reference values were evaluated by the Investigators.
Time frame: Day -14, Day 69
Population: all subjects who received at least one dose of study drug were included in the safety analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Glycopyrrolate Inhalation Solution12.5μg | Number of Clinically Significant Abnormal Laboratory Results Reported During the Study | 0 number of events |
| Glycopyrrolate Inhalation Solution 50μg | Number of Clinically Significant Abnormal Laboratory Results Reported During the Study | 0 number of events |
| Glycopyrrolate Inhalation Solution 100μg | Number of Clinically Significant Abnormal Laboratory Results Reported During the Study | 0 number of events |
| Glycopyrrolate Inhalation Solution 200μg | Number of Clinically Significant Abnormal Laboratory Results Reported During the Study | 0 number of events |
| Glycopyrrolate Inhalation Solution 400μg | Number of Clinically Significant Abnormal Laboratory Results Reported During the Study | 0 number of events |
| Placebo 0.5mL | Number of Clinically Significant Abnormal Laboratory Results Reported During the Study | 0 number of events |
Secondary
Number of Subjects Who Died, Number of Subjects With Treatment Emergent SAEs, Number of Subjects Who Discontinued Due to AE
AE's are defined as existing conditions which worsen or events which occur during the course of the clinical trial after treatment
Time frame: Day 69 (includes dosing Day 1, washout Day 12, safety follow up Day 69)
Population: all subjects who received at least one dose of study drug were included in the safety analysis
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Glycopyrrolate Inhalation Solution12.5μg | Number of Subjects Who Died, Number of Subjects With Treatment Emergent SAEs, Number of Subjects Who Discontinued Due to AE | subjects who died | 0 participants |
| Glycopyrrolate Inhalation Solution12.5μg | Number of Subjects Who Died, Number of Subjects With Treatment Emergent SAEs, Number of Subjects Who Discontinued Due to AE | subjects with treatment emergent SAEs | 0 participants |
| Glycopyrrolate Inhalation Solution12.5μg | Number of Subjects Who Died, Number of Subjects With Treatment Emergent SAEs, Number of Subjects Who Discontinued Due to AE | Subjects whodiscontinued due to an AE | 2 participants |
| Glycopyrrolate Inhalation Solution12.5μg | Number of Subjects Who Died, Number of Subjects With Treatment Emergent SAEs, Number of Subjects Who Discontinued Due to AE | subjects with treatment emergent AEs | 16 participants |
| Glycopyrrolate Inhalation Solution 50μg | Number of Subjects Who Died, Number of Subjects With Treatment Emergent SAEs, Number of Subjects Who Discontinued Due to AE | Subjects whodiscontinued due to an AE | 2 participants |
| Glycopyrrolate Inhalation Solution 50μg | Number of Subjects Who Died, Number of Subjects With Treatment Emergent SAEs, Number of Subjects Who Discontinued Due to AE | subjects with treatment emergent SAEs | 0 participants |
| Glycopyrrolate Inhalation Solution 50μg | Number of Subjects Who Died, Number of Subjects With Treatment Emergent SAEs, Number of Subjects Who Discontinued Due to AE | subjects who died | 0 participants |
| Glycopyrrolate Inhalation Solution 50μg | Number of Subjects Who Died, Number of Subjects With Treatment Emergent SAEs, Number of Subjects Who Discontinued Due to AE | subjects with treatment emergent AEs | 14 participants |
| Glycopyrrolate Inhalation Solution 100μg | Number of Subjects Who Died, Number of Subjects With Treatment Emergent SAEs, Number of Subjects Who Discontinued Due to AE | subjects with treatment emergent AEs | 17 participants |
| Glycopyrrolate Inhalation Solution 100μg | Number of Subjects Who Died, Number of Subjects With Treatment Emergent SAEs, Number of Subjects Who Discontinued Due to AE | Subjects whodiscontinued due to an AE | 2 participants |
| Glycopyrrolate Inhalation Solution 100μg | Number of Subjects Who Died, Number of Subjects With Treatment Emergent SAEs, Number of Subjects Who Discontinued Due to AE | subjects with treatment emergent SAEs | 1 participants |
| Glycopyrrolate Inhalation Solution 100μg | Number of Subjects Who Died, Number of Subjects With Treatment Emergent SAEs, Number of Subjects Who Discontinued Due to AE | subjects who died | 0 participants |
| Glycopyrrolate Inhalation Solution 200μg | Number of Subjects Who Died, Number of Subjects With Treatment Emergent SAEs, Number of Subjects Who Discontinued Due to AE | subjects who died | 0 participants |
| Glycopyrrolate Inhalation Solution 200μg | Number of Subjects Who Died, Number of Subjects With Treatment Emergent SAEs, Number of Subjects Who Discontinued Due to AE | subjects with treatment emergent AEs | 15 participants |
| Glycopyrrolate Inhalation Solution 200μg | Number of Subjects Who Died, Number of Subjects With Treatment Emergent SAEs, Number of Subjects Who Discontinued Due to AE | subjects with treatment emergent SAEs | 0 participants |
| Glycopyrrolate Inhalation Solution 200μg | Number of Subjects Who Died, Number of Subjects With Treatment Emergent SAEs, Number of Subjects Who Discontinued Due to AE | Subjects whodiscontinued due to an AE | 0 participants |
| Glycopyrrolate Inhalation Solution 400μg | Number of Subjects Who Died, Number of Subjects With Treatment Emergent SAEs, Number of Subjects Who Discontinued Due to AE | Subjects whodiscontinued due to an AE | 0 participants |
| Glycopyrrolate Inhalation Solution 400μg | Number of Subjects Who Died, Number of Subjects With Treatment Emergent SAEs, Number of Subjects Who Discontinued Due to AE | subjects with treatment emergent AEs | 13 participants |
| Glycopyrrolate Inhalation Solution 400μg | Number of Subjects Who Died, Number of Subjects With Treatment Emergent SAEs, Number of Subjects Who Discontinued Due to AE | subjects with treatment emergent SAEs | 0 participants |
| Glycopyrrolate Inhalation Solution 400μg | Number of Subjects Who Died, Number of Subjects With Treatment Emergent SAEs, Number of Subjects Who Discontinued Due to AE | subjects who died | 0 participants |
| Placebo 0.5mL | Number of Subjects Who Died, Number of Subjects With Treatment Emergent SAEs, Number of Subjects Who Discontinued Due to AE | subjects with treatment emergent SAEs | 0 participants |
| Placebo 0.5mL | Number of Subjects Who Died, Number of Subjects With Treatment Emergent SAEs, Number of Subjects Who Discontinued Due to AE | Subjects whodiscontinued due to an AE | 0 participants |
| Placebo 0.5mL | Number of Subjects Who Died, Number of Subjects With Treatment Emergent SAEs, Number of Subjects Who Discontinued Due to AE | subjects with treatment emergent AEs | 14 participants |
| Placebo 0.5mL | Number of Subjects Who Died, Number of Subjects With Treatment Emergent SAEs, Number of Subjects Who Discontinued Due to AE | subjects who died | 0 participants |
Secondary
Number of Subjects With Clinically Significant Abnormal Vital Signs Reported During the Study
Vital signs were measured at screening and at each Treatment Visit pre-dose (within 30 minutes prior to dose); post-dose at 30 minutes and 1, 2, 4, 8, 12 and 24 hours; and then at the post study assessment.
Time frame: 0-24 h
Population: all subjects who received at least one does of study drug were included in the safety analysis
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Glycopyrrolate Inhalation Solution12.5μg | Number of Subjects With Clinically Significant Abnormal Vital Signs Reported During the Study | 0 Participants |
| Glycopyrrolate Inhalation Solution 50μg | Number of Subjects With Clinically Significant Abnormal Vital Signs Reported During the Study | 0 Participants |
| Glycopyrrolate Inhalation Solution 100μg | Number of Subjects With Clinically Significant Abnormal Vital Signs Reported During the Study | 0 Participants |
| Glycopyrrolate Inhalation Solution 200μg | Number of Subjects With Clinically Significant Abnormal Vital Signs Reported During the Study | 0 Participants |
| Glycopyrrolate Inhalation Solution 400μg | Number of Subjects With Clinically Significant Abnormal Vital Signs Reported During the Study | 0 Participants |
| Placebo 0.5mL | Number of Subjects With Clinically Significant Abnormal Vital Signs Reported During the Study | 0 Participants |
Secondary
Number of Subjects With Clinically Significant ECG Parameters Reported During the Study
ECGs were recorded at screening and at each study treatment visit pre-dose (within 30 minutes prior to dose); post-dose at 30 minutes and 1, 2, 4, 8, 12 and 24 hours; and then at the post study assessment.
Time frame: 0 to 24h
Population: all subjects who received at least one dose of study drug were included in the safety analysis
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Glycopyrrolate Inhalation Solution12.5μg | Number of Subjects With Clinically Significant ECG Parameters Reported During the Study | 0 Participants |
| Glycopyrrolate Inhalation Solution 50μg | Number of Subjects With Clinically Significant ECG Parameters Reported During the Study | 0 Participants |
| Glycopyrrolate Inhalation Solution 100μg | Number of Subjects With Clinically Significant ECG Parameters Reported During the Study | 0 Participants |
| Glycopyrrolate Inhalation Solution 200μg | Number of Subjects With Clinically Significant ECG Parameters Reported During the Study | 0 Participants |
| Glycopyrrolate Inhalation Solution 400μg | Number of Subjects With Clinically Significant ECG Parameters Reported During the Study | 0 Participants |
| Placebo 0.5mL | Number of Subjects With Clinically Significant ECG Parameters Reported During the Study | 0 Participants |
Secondary
Percentage of Subjects With Treatment Emergent AEs
AE's are defined as existing conditions which worsen or events which occur during the course of the clinical trial after treatment
Time frame: Day 69 (includes dosing Day 1, washout Day 12, safety follow up Day 69)
Population: all subjects who received at least one dose of study drug were included in the safety analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Glycopyrrolate Inhalation Solution12.5μg | Percentage of Subjects With Treatment Emergent AEs | 41.0 percentage of participants |
| Glycopyrrolate Inhalation Solution 50μg | Percentage of Subjects With Treatment Emergent AEs | 36.8 percentage of participants |
| Glycopyrrolate Inhalation Solution 100μg | Percentage of Subjects With Treatment Emergent AEs | 45.9 percentage of participants |
| Glycopyrrolate Inhalation Solution 200μg | Percentage of Subjects With Treatment Emergent AEs | 40.5 percentage of participants |
| Glycopyrrolate Inhalation Solution 400μg | Percentage of Subjects With Treatment Emergent AEs | 35.1 percentage of participants |
| Placebo 0.5mL | Percentage of Subjects With Treatment Emergent AEs | 37.8 percentage of participants |
Secondary
t1/2; Plasma Half-life
Pk parameters are calculated from glycopyrrolate plasma concentration analysed from serial blood samples collected between 0 and 12 hr
Time frame: 0 to 12 hour
Population: All subjects who received at least one dose of EP-101 and who have sufficient blood samples taken to obtain a plasma concentration by time profile and have no major protocol violations were included in the PK analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Glycopyrrolate Inhalation Solution 50μg | t1/2; Plasma Half-life | 0.8949 hours | Geometric Coefficient of Variation 2.3707 |
| Glycopyrrolate Inhalation Solution 100μg | t1/2; Plasma Half-life | 3.0137 hours | Geometric Coefficient of Variation 50.7557 |
| Glycopyrrolate Inhalation Solution 200μg | t1/2; Plasma Half-life | 3.1663 hours | Geometric Coefficient of Variation 45.4839 |
| Glycopyrrolate Inhalation Solution 400μg | t1/2; Plasma Half-life | 4.1238 hours | Geometric Coefficient of Variation 63.5353 |
Secondary
Tmax; Time to Maximum Observed Plasma Concentration
Pk parameters are calculated from glycopyrrolate plasma concentration analysed from serial blood samples collected between 0 and 12 hr
Time frame: 0 to 12 hours
Population: All subjects who received at least one dose of EP-101 and who have sufficient blood samples taken to obtain a plasma concentration by time profile and have no major protocol violations were included in the PK analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Glycopyrrolate Inhalation Solution12.5μg | Tmax; Time to Maximum Observed Plasma Concentration | 0.165 hours |
| Glycopyrrolate Inhalation Solution 50μg | Tmax; Time to Maximum Observed Plasma Concentration | 0.320 hours |
| Glycopyrrolate Inhalation Solution 100μg | Tmax; Time to Maximum Observed Plasma Concentration | 0.260 hours |
| Glycopyrrolate Inhalation Solution 200μg | Tmax; Time to Maximum Observed Plasma Concentration | 0.275 hours |
| Glycopyrrolate Inhalation Solution 400μg | Tmax; Time to Maximum Observed Plasma Concentration | 0.180 hours |