Chronic Obstructive Pulmonary Disease
Conditions
Keywords
Emphysema, Chronic bronchitis, COPD, Chronic Obstructive Pulmonary Disease
Brief summary
The study assessed the safety and ability of several doses of an orally inhaled medicine \[ie, Glycopyrrolate Inhalation Solution = GIS\] to improve airflow in the lungs when delivered with an electronic eFlow nebulizer system in patients with Chronic Obstructive Pulmonary Disease (COPD). The study was conducted in 12 patients in 2 parts. Part 1 was designed to find the once-a- day GIS dose that produced the highest improvement in lung airflow. Part 2 tested the GIS dose with the highest improvement in lung airflow and a placebo (ie, no drug) delivered by a general purpose nebulizer. The airflow improvements of the same GIS dose were compared between the two nebulizer systems to determine what effect the device had on GIS delivery.
Detailed description
In Part I, 12 subjects were randomly allocated to one of 2 cohorts, running in parallel. The 6 cohort 1 subjects received 25 mg and then 200 mg during their treatment periods 1 and 2, respectively. The 6 cohort 2 subjects received 75mg, 500mg, and 1000 mg during their treatment periods 1, 2, and 3, respectively. During Part II of the study, the same 12 subjects from Part I were randomized to receive either 200 mg jet or placebo in a 1:1 ratio.
Interventions
DRUGGlycopyrrolate Inhalation Solution 25mg
25 μg oral inhalation via eFlow Nebulizer, once daily
DRUGGlycopyrrolate Inhalation Solution 75mg
75 μg oral inhalation via eFlow Nebulizer, once daily
DRUGGlycopyrrolate Inhalation Solution 200mg
200 μg oral inhalation via eFlow Nebulizer, once daily
DRUGGlycopyrrolate Inhalation Solution 200mg Jet
200 μg oral inhalation via inhalation via jet nebulizer, once daily
DRUGGlycopyrrolate Inhalation Solution 500mg
500 μg oral inhalation via eFlow nebulizer, once daily
DRUGGlycopyrrolate Inhalation Solution1000mg
1000 μg oral inhalation via eFlow nebulizer, once daily
DRUGPlacebo
Placebo 0.5 mL oral inhalation via jet nebulizer, once daily
Sponsors
Sunovion Respiratory Development Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
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 years, or 10 packs/day for 1 year) 4. Post-bronchodilator FEV1 40-80% of predicted normal 5. Post-bronchodilator FEV1/FVC ratio \< 0.70 6. Improvement in FEV1 \>12% (minimum 150 mL) following inhalation of ipratropium bromide 7. Ability to perform reproducible spirometry according to the ATS/ERS guidelines 8. If female and of childbearing potential, must have had a negative pregnancy test and was not lactating at the Screening Visit, and was using one of the following acceptable means of birth control throughout the study: * Post-menopausal for at least two years * Surgically sterile * 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 9. Willing and able to provide written informed consent
Exclusion criteria
1. 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 patients at risk or which would compromise the quality of the study data; including but not limited to cardiovascular disease, myocardial infraction, hypertension, arrhythmia, diabetes, neurological or neuromuscular disease, liver disease, gastrointestinal disease or electrolyte abnormalities. 2. Recent history of an exacerbation of airway disease within 3 months or need for increased treatments for COPD within 6 weeks prior to the Screening Visit. 3. Regular use of daily oxygen therapy. 4. Use of systemic (e.g., intramuscular or intravenous) steroids within 3 months prior to the Screening Visit 5. Respiratory tract infection within 6 weeks prior to the Screening Visit 6. History of tuberculosis, bronchiectasis or other non-specific pulmonary disease 7. History of urinary retention or bladder neck obstruction type symptoms 8. History of narrow-angle glaucoma 9. Current or recent history (previous 12 months) of excessive use or abuse of alcohol 10. Current evidence or history of abusing legal drugs or the use of illegal drugs or substances 11. History of hypersensitivity or intolerance to aerosol medications 12. Participation in another investigational drug study where drug was received within 30 days prior to the Screening Visit
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects Who Died | 0-47 days | — |
| Number of Subjects With Treatment Emergent SAEs | 0-47 days | AEs are defined as existing conditions which worsen or events which occur during the course of the clinical trial after treatment.AEs are defined as existing conditions which worsen or events which occur during the course of the clinical trial after treatment. SAEs are AEs that result in the following outcomes: death, are life-threatening, persistent or significant disability/incapacity, congenital anomaly/birth defect, or important medical events that may have been considered a SAE when, based upon appropriate medical judgment, they may have jeopardized the subject and may have required medical or surgical intervention to prevent one of the outcomes listed in the definition. |
| Number of Subjects Who Discontinued Due to AE | 0-47 days | AEs are defined as existing conditions which worsen or events which occur during the course of the clinical trial after treatment. |
| Percentage of Subjects With Treatment Emergent AEs | 0-47 days | AEs 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 | 30 hrs post dose | Vital signs were measured at screening, during the study (pre-dose, and 30 and 60 minutes and 2, 4, 8, 12, 24 and 30 hours post-dose) and at post study assessment. The clinical significance of each out of normal range vital sign parameter was determined by the investigator during the study. |
| Number of Subjects With Clinically Significant Abnormal Laboratory Results Reported During the Study | day 47 (post studyfollow-up assessment) | Clinical safety lab parameters were collected at screening and at the post study follow-up assessment. The clinical significance of each out of normal range laboratory parameter was determined by the investigator during the study. |
| Number of Subjects With Clinically Significant ECG Parameters Reported During the Study | 30hr post dose | ECGs were measured at screening, during the study (pre-dose, and 30 and 60 minutes and 2, 4, 8, 12, 24 and 30 hours post-dose) and at post study follow-up assessment. |
| Number of Subjects With Treatment Emergent AEs | 0-47 days | AEs are defined as existing conditions which worsen or events which occur during the course of the clinical trial after treatment. SAEs are AEs that result in the following outcomes: death, are life-threatening, persistent or significant disability/incapacity, congenital anomaly/birth defect, or important medical events that may have been considered a SAE when, based upon appropriate medical judgment, they may have jeopardized the subject and may have required medical or surgical intervention to prevent one of the outcomes listed in the definition. |
Secondary
| 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 spirometry value collected at 24 hours post dose within each Treatment Period. |
| Peak FEV1 (Percent Change) | 0 to 4hr | Spirometry measurements were conducted in accordance with the current ATS/ERS 2005 guidelines. |
| Peak FEV1 (Change From Baseline ) | 0 to 4hr | Spirometry measurements were conducted in accordance with the current ATS/ERS 2005 guidelines. |
| FEV1 AUC0-24 Area Under the FEV1 Over Time Curve (Change From Baseline) | 0 to 24hr post dose | Spirometry measurements were conducted in accordance with the current ATS/ERS 2005 guidelines. |
| Cmax Maximum Observed Plasma Concentration | 0 to 12 hours post dose | Pk parameters are calculated from glycopyrrolate plasma concentration analysed from serial blood samples collected between 0 and 12 hr |
| Tmax Time to Maximum Observed Plasma Concentration | 0 to 12 hours post dose | 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 the Last Quantifiable Concentration | 0 to 12 hourr post dose | 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 hours post dose | 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 hours post-dose | Pk parameters are calculated from glycopyrrolate plasma concentration analysed from serial blood samples collected between 0 and 12 hr. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 25mg Glycopyrrolate, 200mg Gloycopyrrolate subjects received 25mg Glycopyrrolate then 200mg Glycopyrrolate in part 1- in part 2 subjects from this group either received 200mg Glycopyrrolate or placebo | 6 |
| 75mg Glycopyrrolate,500mg Glycopyrrolate,1000mg Glycopyrrolate subjects received 75mg Glycoprrolate, then, 500mg Glycopyrrolate, then 1000mg Glycopyrrolate in part 1 - in part 2 subjects from this group received either 200mg Glycopyrrolate or placebo | 6 |
| 200mg Glycopyrrolate Jet subjects received 200mg Glycopyrrolate | 0 |
| Placebo subjects received placebo | 0 |
| Total | 12 |
Baseline characteristics
| Characteristic | 75mg Glycopyrrolate,500mg Glycopyrrolate,1000mg Glycopyrrolate | 25mg Glycopyrrolate, 200mg Gloycopyrrolate | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 3 Participants | 4 Participants | 7 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants | 2 Participants | 5 Participants |
| Age, Continuous | 63.5 years STANDARD_DEVIATION 8.89 | 66.2 years STANDARD_DEVIATION 3.82 | 41.67 years STANDARD_DEVIATION 58.33 |
| Region of Enrollment United Kingdom | 6 participants | 6 participants | 12 participants |
| Sex: Female, Male Female | 2 Participants | 3 Participants | 5 Participants |
| Sex: Female, Male Male | 4 Participants | 3 Participants | 7 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 | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 2 / 6 | 2 / 6 | 4 / 6 | 2 / 6 | 0 / 6 | 2 / 6 | 1 / 6 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 |
Outcome results
Primary
Number of Subjects Who Died
Time frame: 0-47 days
Population: all subjects who received at least one dose of study medication were included in the safety analysis.. A subject received more than one treatment type throughout the study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Glycopyrrolate Inhalation Solution 25mg | Number of Subjects Who Died | 0 Participants |
| Glycopyrrolate Inhalation Solution 75mg | Number of Subjects Who Died | 0 Participants |
| Glycopyrrolate Inhalation Solution 200mg | Number of Subjects Who Died | 0 Participants |
| Glycopyrrolate Inhalation Solution 200mg Jet | Number of Subjects Who Died | 0 Participants |
| Glycopyrrolate Inhalation Solution 500mg | Number of Subjects Who Died | 0 Participants |
| Glycopyrrolate Inhalation Solution1000mg | Number of Subjects Who Died | 0 Participants |
| Placebo 0.5 mL | Number of Subjects Who Died | 0 Participants |
Primary
Number of Subjects Who Discontinued Due to AE
AEs are defined as existing conditions which worsen or events which occur during the course of the clinical trial after treatment.
Time frame: 0-47 days
Population: all subjects who received at least one dose of study medication were included in the safety analysis. . A subject received more than one treatment type throughout the study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Glycopyrrolate Inhalation Solution 25mg | Number of Subjects Who Discontinued Due to AE | 0 Participants |
| Glycopyrrolate Inhalation Solution 75mg | Number of Subjects Who Discontinued Due to AE | 0 Participants |
| Glycopyrrolate Inhalation Solution 200mg | Number of Subjects Who Discontinued Due to AE | 0 Participants |
| Glycopyrrolate Inhalation Solution 200mg Jet | Number of Subjects Who Discontinued Due to AE | 0 Participants |
| Glycopyrrolate Inhalation Solution 500mg | Number of Subjects Who Discontinued Due to AE | 0 Participants |
| Glycopyrrolate Inhalation Solution1000mg | Number of Subjects Who Discontinued Due to AE | 0 Participants |
| Placebo 0.5 mL | Number of Subjects Who Discontinued Due to AE | 0 Participants |
Primary
Number of Subjects With Clinically Significant Abnormal Laboratory Results Reported During the Study
Clinical safety lab parameters were collected at screening and at the post study follow-up assessment. The clinical significance of each out of normal range laboratory parameter was determined by the investigator during the study.
Time frame: day 47 (post studyfollow-up assessment)
Population: all subjects who received at least one dose of study medication were included in the safety analysis. A subject received more than one treatment type throughout the study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Glycopyrrolate Inhalation Solution 25mg | Number of Subjects With Clinically Significant Abnormal Laboratory Results Reported During the Study | 0 Participants |
| Glycopyrrolate Inhalation Solution 75mg | Number of Subjects With Clinically Significant Abnormal Laboratory Results Reported During the Study | 0 Participants |
| Glycopyrrolate Inhalation Solution 200mg | Number of Subjects With Clinically Significant Abnormal Laboratory Results Reported During the Study | 0 Participants |
| Glycopyrrolate Inhalation Solution 200mg Jet | Number of Subjects With Clinically Significant Abnormal Laboratory Results Reported During the Study | 0 Participants |
| Glycopyrrolate Inhalation Solution 500mg | Number of Subjects With Clinically Significant Abnormal Laboratory Results Reported During the Study | 0 Participants |
| Glycopyrrolate Inhalation Solution1000mg | Number of Subjects With Clinically Significant Abnormal Laboratory Results Reported During the Study | 0 Participants |
| Placebo 0.5 mL | Number of Subjects With Clinically Significant Abnormal Laboratory Results Reported During the Study | 0 Participants |
Primary
Number of Subjects With Clinically Significant Abnormal Laboratory Results Reported During the Study
Clinical safety lab parameters were collected at screening and at the post study follow-up assessment. The clinical significance of each out of normal range laboratory parameter was determined by the investigator during the study.
Time frame: post study follow-up assessment (Day 47)
Population: all subjects who received at least one dose of study medication were included in the safety analysis. A subject received more than one treatment type throughout the study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Glycopyrrolate Inhalation Solution 25mg | Number of Subjects With Clinically Significant Abnormal Laboratory Results Reported During the Study | 0 Participants |
| Glycopyrrolate Inhalation Solution 75mg | Number of Subjects With Clinically Significant Abnormal Laboratory Results Reported During the Study | 0 Participants |
| Glycopyrrolate Inhalation Solution 200mg | Number of Subjects With Clinically Significant Abnormal Laboratory Results Reported During the Study | 0 Participants |
| Glycopyrrolate Inhalation Solution 200mg Jet | Number of Subjects With Clinically Significant Abnormal Laboratory Results Reported During the Study | 0 Participants |
| Glycopyrrolate Inhalation Solution 500mg | Number of Subjects With Clinically Significant Abnormal Laboratory Results Reported During the Study | 0 Participants |
| Glycopyrrolate Inhalation Solution1000mg | Number of Subjects With Clinically Significant Abnormal Laboratory Results Reported During the Study | 0 Participants |
| Placebo 0.5 mL | Number of Subjects With Clinically Significant Abnormal Laboratory Results Reported During the Study | 0 Participants |
Primary
Number of Subjects With Clinically Significant Abnormal Vital Signs Reported During the Study
Vital signs were measured at screening, during the study (pre-dose, and 30 and 60 minutes and 2, 4, 8, 12, 24 and 30 hours post-dose) and at post study assessment. The clinical significance of each out of normal range vital sign parameter was determined by the investigator during the study.
Time frame: 30 hrs post dose
Population: all subjects who received at least one dose of study medication were included in the safety analysis. . A subject received more than one treatment type throughout the study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Glycopyrrolate Inhalation Solution 25mg | Number of Subjects With Clinically Significant Abnormal Vital Signs Reported During the Study | 0 Participants |
| Glycopyrrolate Inhalation Solution 75mg | Number of Subjects With Clinically Significant Abnormal Vital Signs Reported During the Study | 0 Participants |
| Glycopyrrolate Inhalation Solution 200mg | Number of Subjects With Clinically Significant Abnormal Vital Signs Reported During the Study | 0 Participants |
| Glycopyrrolate Inhalation Solution 200mg Jet | Number of Subjects With Clinically Significant Abnormal Vital Signs Reported During the Study | 0 Participants |
| Glycopyrrolate Inhalation Solution 500mg | Number of Subjects With Clinically Significant Abnormal Vital Signs Reported During the Study | 0 Participants |
| Glycopyrrolate Inhalation Solution1000mg | Number of Subjects With Clinically Significant Abnormal Vital Signs Reported During the Study | 0 Participants |
| Placebo 0.5 mL | Number of Subjects With Clinically Significant Abnormal Vital Signs Reported During the Study | 0 Participants |
Primary
Number of Subjects With Clinically Significant ECG Parameters Reported During the Study
ECGs were measured at screening, during the study (pre-dose, and 30 and 60 minutes and 2, 4, 8, 12, 24 and 30 hours post-dose) and at post study follow-up assessment.
Time frame: 30hr post dose
Population: all subjects who received at least one dose of study medication were included in the safety analysis. A subject received more than one treatment type throughout the study
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Glycopyrrolate Inhalation Solution 25mg | Number of Subjects With Clinically Significant ECG Parameters Reported During the Study | 0 Participants |
| Glycopyrrolate Inhalation Solution 75mg | Number of Subjects With Clinically Significant ECG Parameters Reported During the Study | 0 Participants |
| Glycopyrrolate Inhalation Solution 200mg | Number of Subjects With Clinically Significant ECG Parameters Reported During the Study | 0 Participants |
| Glycopyrrolate Inhalation Solution 200mg Jet | Number of Subjects With Clinically Significant ECG Parameters Reported During the Study | 0 Participants |
| Glycopyrrolate Inhalation Solution 500mg | Number of Subjects With Clinically Significant ECG Parameters Reported During the Study | 0 Participants |
| Glycopyrrolate Inhalation Solution1000mg | Number of Subjects With Clinically Significant ECG Parameters Reported During the Study | 0 Participants |
| Placebo 0.5 mL | Number of Subjects With Clinically Significant ECG Parameters Reported During the Study | 0 Participants |
Primary
Number of Subjects With Treatment Emergent AEs
AEs are defined as existing conditions which worsen or events which occur during the course of the clinical trial after treatment. SAEs are AEs that result in the following outcomes: death, are life-threatening, persistent or significant disability/incapacity, congenital anomaly/birth defect, or important medical events that may have been considered a SAE when, based upon appropriate medical judgment, they may have jeopardized the subject and may have required medical or surgical intervention to prevent one of the outcomes listed in the definition.
Time frame: 0-47 days
Population: all subjects who received at least one dose of study medication were included in the safety analysis. A subject received more than one treatment type throughout the study
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Glycopyrrolate Inhalation Solution 25mg | Number of Subjects With Treatment Emergent AEs | 2 Participants |
| Glycopyrrolate Inhalation Solution 75mg | Number of Subjects With Treatment Emergent AEs | 2 Participants |
| Glycopyrrolate Inhalation Solution 200mg | Number of Subjects With Treatment Emergent AEs | 4 Participants |
| Glycopyrrolate Inhalation Solution 200mg Jet | Number of Subjects With Treatment Emergent AEs | 2 Participants |
| Glycopyrrolate Inhalation Solution 500mg | Number of Subjects With Treatment Emergent AEs | 0 Participants |
| Glycopyrrolate Inhalation Solution1000mg | Number of Subjects With Treatment Emergent AEs | 2 Participants |
| Placebo 0.5 mL | Number of Subjects With Treatment Emergent AEs | 1 Participants |
Primary
Number of Subjects With Treatment Emergent SAEs
AEs are defined as existing conditions which worsen or events which occur during the course of the clinical trial after treatment.AEs are defined as existing conditions which worsen or events which occur during the course of the clinical trial after treatment. SAEs are AEs that result in the following outcomes: death, are life-threatening, persistent or significant disability/incapacity, congenital anomaly/birth defect, or important medical events that may have been considered a SAE when, based upon appropriate medical judgment, they may have jeopardized the subject and may have required medical or surgical intervention to prevent one of the outcomes listed in the definition.
Time frame: 0-47 days
Population: all subjects who received at least one dose of study medication were included in the safety analysis.. A subject received more than one treatment type throughout the study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Glycopyrrolate Inhalation Solution 25mg | Number of Subjects With Treatment Emergent SAEs | 0 Participants |
| Glycopyrrolate Inhalation Solution 75mg | Number of Subjects With Treatment Emergent SAEs | 0 Participants |
| Glycopyrrolate Inhalation Solution 200mg | Number of Subjects With Treatment Emergent SAEs | 0 Participants |
| Glycopyrrolate Inhalation Solution 200mg Jet | Number of Subjects With Treatment Emergent SAEs | 0 Participants |
| Glycopyrrolate Inhalation Solution 500mg | Number of Subjects With Treatment Emergent SAEs | 0 Participants |
| Glycopyrrolate Inhalation Solution1000mg | Number of Subjects With Treatment Emergent SAEs | 0 Participants |
| Placebo 0.5 mL | Number of Subjects With Treatment Emergent SAEs | 0 Participants |
Primary
Percentage of Subjects With Treatment Emergent AEs
AEs are defined as existing conditions which worsen or events which occur during the course of the clinical trial after treatment.
Time frame: 0-47 days
Population: all subjects who received at least one dose of study medication were included in the safety analysis. . A subject received more than one treatment type throughout the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Glycopyrrolate Inhalation Solution 25mg | Percentage of Subjects With Treatment Emergent AEs | 33.3 percentage of participants |
| Glycopyrrolate Inhalation Solution 75mg | Percentage of Subjects With Treatment Emergent AEs | 33.3 percentage of participants |
| Glycopyrrolate Inhalation Solution 200mg | Percentage of Subjects With Treatment Emergent AEs | 66.7 percentage of participants |
| Glycopyrrolate Inhalation Solution 200mg Jet | Percentage of Subjects With Treatment Emergent AEs | 33.3 percentage of participants |
| Glycopyrrolate Inhalation Solution 500mg | Percentage of Subjects With Treatment Emergent AEs | 0.0 percentage of participants |
| Glycopyrrolate Inhalation Solution1000mg | Percentage of Subjects With Treatment Emergent AEs | 33.3 percentage of participants |
| Placebo 0.5 mL | Percentage of Subjects With Treatment Emergent AEs | 16.7 percentage of participants |
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 hours post dose
Population: All subjects who received at least one dose of study medication and who have sufficient blood samples taken to obtain a plasma concentration by time profile were included in the PK analysis. A subject received more than one treatment type throughout the study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Glycopyrrolate Inhalation Solution 25mg | AUC0-inf Area Under the Plasma Concentration-time Curve From Time Zero to Infinity | 563.416 pg*h/mL | Standard Deviation 235.418 |
| Glycopyrrolate Inhalation Solution 75mg | AUC0-inf Area Under the Plasma Concentration-time Curve From Time Zero to Infinity | 65.013 pg*h/mL | Standard Deviation 16.75 |
| Glycopyrrolate Inhalation Solution 200mg | AUC0-inf Area Under the Plasma Concentration-time Curve From Time Zero to Infinity | 2491.803 pg*h/mL | Standard Deviation 736.426 |
| Glycopyrrolate Inhalation Solution 200mg Jet | AUC0-inf Area Under the Plasma Concentration-time Curve From Time Zero to Infinity | 5271.099 pg*h/mL | Standard Deviation 1096.862 |
Secondary
AUC0-t Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable 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 hourr post dose
Population: All subjects who received at least one dose of study medication and who have sufficient blood samples taken to obtain a plasma concentration by time profile were included in the PK analysis.A subject received more than one treatment type throughout the study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Glycopyrrolate Inhalation Solution 25mg | AUC0-t Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Concentration | 429.335 pg*h/mL | Standard Deviation 192.699 |
| Glycopyrrolate Inhalation Solution 75mg | AUC0-t Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Concentration | 26.176 pg*h/mL | Standard Deviation 16.17 |
| Glycopyrrolate Inhalation Solution 200mg | AUC0-t Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Concentration | 2014.276 pg*h/mL | Standard Deviation 609.911 |
| Glycopyrrolate Inhalation Solution 200mg Jet | AUC0-t Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Concentration | 4084.763 pg*h/mL | Standard Deviation 827.225 |
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 hours post dose
Population: All subjects who received at least one dose of study medication and who have sufficient blood samples taken to obtain a plasma concentration by time profile were included in the PK . A subject received more than one treatment type throughout the study.~analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Glycopyrrolate Inhalation Solution 25mg | Cmax Maximum Observed Plasma Concentration | 177.242 pg/mL | Standard Deviation 61.469 |
| Glycopyrrolate Inhalation Solution 75mg | Cmax Maximum Observed Plasma Concentration | 75.530 pg/mL | Standard Deviation 64.95 |
| Glycopyrrolate Inhalation Solution 200mg | Cmax Maximum Observed Plasma Concentration | 749.872 pg/mL | Standard Deviation 219.696 |
| Glycopyrrolate Inhalation Solution 200mg Jet | Cmax Maximum Observed Plasma Concentration | 1534.057 pg/mL | Standard Deviation 442.581 |
Secondary
FEV1 AUC0-24 Area Under the FEV1 Over Time Curve (Change From Baseline)
Spirometry measurements were conducted in accordance with the current ATS/ERS 2005 guidelines.
Time frame: 0 to 24hr post dose
Population: All subjects who received at least one dose of study medication and have at least one post baselineefficacy measurement were included in the efficacy population. A subject received more than one treatment type throughout the study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Glycopyrrolate Inhalation Solution 25mg | FEV1 AUC0-24 Area Under the FEV1 Over Time Curve (Change From Baseline) | 1.59 liters | Standard Deviation 3.27 |
| Glycopyrrolate Inhalation Solution 75mg | FEV1 AUC0-24 Area Under the FEV1 Over Time Curve (Change From Baseline) | 3.10 liters | Standard Deviation 2.27 |
| Glycopyrrolate Inhalation Solution 200mg | FEV1 AUC0-24 Area Under the FEV1 Over Time Curve (Change From Baseline) | 3.19 liters | Standard Deviation 1.14 |
| Glycopyrrolate Inhalation Solution 200mg Jet | FEV1 AUC0-24 Area Under the FEV1 Over Time Curve (Change From Baseline) | 1.35 liters | Standard Deviation 2.74 |
| Glycopyrrolate Inhalation Solution 500mg | FEV1 AUC0-24 Area Under the FEV1 Over Time Curve (Change From Baseline) | 1.53 liters | Standard Deviation 2.05 |
| Glycopyrrolate Inhalation Solution1000mg | FEV1 AUC0-24 Area Under the FEV1 Over Time Curve (Change From Baseline) | 3.08 liters | Standard Deviation 1.47 |
| Placebo 0.5 mL | FEV1 AUC0-24 Area Under the FEV1 Over Time Curve (Change From Baseline) | -0.11 liters | Standard Deviation 1.89 |
Secondary
Peak FEV1 (Change From Baseline )
Spirometry measurements were conducted in accordance with the current ATS/ERS 2005 guidelines.
Time frame: 0 to 4hr
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.. A subject received more than one treatment type throughout the study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Glycopyrrolate Inhalation Solution 25mg | Peak FEV1 (Change From Baseline ) | 0.212 liters | Standard Deviation 0.086 |
| Glycopyrrolate Inhalation Solution 75mg | Peak FEV1 (Change From Baseline ) | 0.255 liters | Standard Deviation 0.068 |
| Glycopyrrolate Inhalation Solution 200mg | Peak FEV1 (Change From Baseline ) | 0.303 liters | Standard Deviation 0.055 |
| Glycopyrrolate Inhalation Solution 200mg Jet | Peak FEV1 (Change From Baseline ) | 0.233 liters | Standard Deviation 0.144 |
| Glycopyrrolate Inhalation Solution 500mg | Peak FEV1 (Change From Baseline ) | 0.177 liters | Standard Deviation 0.061 |
| Glycopyrrolate Inhalation Solution1000mg | Peak FEV1 (Change From Baseline ) | 0.283 liters | Standard Deviation 0.069 |
| Placebo 0.5 mL | Peak FEV1 (Change From Baseline ) | 0.120 liters | Standard Deviation 0.057 |
Secondary
Peak FEV1 (Percent Change)
Spirometry measurements were conducted in accordance with the current ATS/ERS 2005 guidelines.
Time frame: 0 to 4hr
Population: all subjects who received at least one dose of the study medication and have at least one post baseline efficacy measurement were included in the efficacy population. . A subject received more than one treatment type throughout the study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Glycopyrrolate Inhalation Solution 25mg | Peak FEV1 (Percent Change) | 17.12 percent change | Standard Deviation 9.07 |
| Glycopyrrolate Inhalation Solution 75mg | Peak FEV1 (Percent Change) | 15.60 percent change | Standard Deviation 4.2 |
| Glycopyrrolate Inhalation Solution 200mg | Peak FEV1 (Percent Change) | 22.98 percent change | Standard Deviation 4.99 |
| Glycopyrrolate Inhalation Solution 200mg Jet | Peak FEV1 (Percent Change) | 19.28 percent change | Standard Deviation 13.1 |
| Glycopyrrolate Inhalation Solution 500mg | Peak FEV1 (Percent Change) | 11.47 percent change | Standard Deviation 6.86 |
| Glycopyrrolate Inhalation Solution1000mg | Peak FEV1 (Percent Change) | 16.87 percent change | Standard Deviation 6.83 |
| Placebo 0.5 mL | Peak FEV1 (Percent Change) | 6.80 percent change | Standard Deviation 2.91 |
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 hours post-dose
Population: Subjects who received at least one dose of study medication and have sufficient blood samples taken to obtain a plasma concentration by time profile were included in the PK analysis.Subject received more than one treatment type throughout the study~samples taken to obtain a plasma concentration by time profile were included in the PK analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Glycopyrrolate Inhalation Solution 25mg | t1/2 Plasma Half-life | 2.947 hour | Standard Deviation 1.996 |
| Glycopyrrolate Inhalation Solution 75mg | t1/2 Plasma Half-life | 0.778 hour | Standard Deviation 0.465 |
| Glycopyrrolate Inhalation Solution 200mg | t1/2 Plasma Half-life | 6.298 hour | Standard Deviation 1.45 |
| Glycopyrrolate Inhalation Solution 200mg Jet | t1/2 Plasma Half-life | 7.573 hour | Standard Deviation 1.031 |
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 post dose
Population: All subjects who received at least one dose of study medication and who have sufficient blood samples taken to obtain a plasma concentration by time profile were included in the PK analysis. A subject received more than one treatment type throughout the study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Glycopyrrolate Inhalation Solution 25mg | Tmax Time to Maximum Observed Plasma Concentration | .025 hours | Standard Deviation 0.088 |
| Glycopyrrolate Inhalation Solution 75mg | Tmax Time to Maximum Observed Plasma Concentration | 0.08 hours | Standard Deviation 0.088 |
| Glycopyrrolate Inhalation Solution 200mg | Tmax Time to Maximum Observed Plasma Concentration | 0.25 hours | Standard Deviation 0.069 |
| Glycopyrrolate Inhalation Solution 200mg Jet | Tmax Time to Maximum Observed Plasma Concentration | 0.17 hours | Standard Deviation 0.093 |
Secondary
Trough FEV1 (Change From Baseline)
Spirometry measurements were conducted in accordance with the current ATS/ERS 2005 guidelines. Trough FEV1 was defined as the spirometry value collected at 24 hours post dose within each Treatment Period.
Time frame: 24hr 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. A subject received more than one treatment type throughout the study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Glycopyrrolate Inhalation Solution 25mg | Trough FEV1 (Change From Baseline) | 0.038 liters | Standard Deviation 0.157 |
| Glycopyrrolate Inhalation Solution 75mg | Trough FEV1 (Change From Baseline) | 0.087 liters | Standard Deviation 0.062 |
| Glycopyrrolate Inhalation Solution 200mg | Trough FEV1 (Change From Baseline) | 0.138 liters | Standard Deviation 0.079 |
| Glycopyrrolate Inhalation Solution 200mg Jet | Trough FEV1 (Change From Baseline) | -0.013 liters | Standard Deviation 0.098 |
| Glycopyrrolate Inhalation Solution 500mg | Trough FEV1 (Change From Baseline) | -0.017 liters | Standard Deviation 0.168 |
| Glycopyrrolate Inhalation Solution1000mg | Trough FEV1 (Change From Baseline) | 0.065 liters | Standard Deviation 0.072 |
| Placebo 0.5 mL | Trough FEV1 (Change From Baseline) | -0.030 liters | Standard Deviation 0.07 |