Back to resultsDose Ranging Study of Glycopyrronium Bromide in Patients With Moderate or Severe Chronic Obstructive Pulmonary Disease
Primary Purpose
Chronic Obstructive Pulmonary Disease
Status
Completed
Phase
Phase 2
Locations
United Kingdom
Study Type
Interventional
Intervention
glycopyrronium bromide
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Obstructive Pulmonary Disease focused on measuring glycopyrronium bromide, glycopyrrolate, oral inhalation, COPD, chronic obstructive pulmonary disease, lung function, pharmacokinetics, tolerability, safety, cross-over, single-dose, dose-ranging
Eligibility Criteria
Inclusion Criteria:
- Male or female age 40-75 years, inclusive
- A clinical diagnosis of moderate to severe COPD (GOLD guidelines)
- Current smokers or ex-smokers with at least 10-pack year smoking history
- Post-bronchodilator FEV1/FVC ratio < 70 % at Screen
- Post-bronchodilator FEV1 ≥ 40 % to < 80 % of predicted at Screen
- Demonstrated to be responsive to ipratropium (defined as at least an 100ml increase in FEV1 following ipratropium 80 µg)
- Ability to perform acceptable spirometry (ATS/ERS guidelines)
- Willing and able to provide written informed consent
Exclusion Criteria:
- Females who are pregnant or lactating at the Screening Visit, or if of childbearing potential not using an acceptable means of birth control throughout the study (defined in protocol)
- 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 (defined in protocol)
- Recent history of hospitalisation due to an exacerbation of airway disease within three months prior to the Screening Visit or randomisation
- Need for increased treatments of COPD within six weeks prior to the Screening Visit or randomisation
- Primary diagnosis of asthma
- Prior lung volume reductions surgery or history of chest/lung irradiation
- Regular use of daily oxygen therapy
- Use of systemic steroids within three months prior to the Screening Visit or during the run-in period
- Respiratory tract infection within six weeks prior to the Screening Visit.
- History of tuberculosis, bronchiectasis or other non-specific pulmonary disease
- History of urinary retention or bladder neck obstructive type symptoms
- History of narrow-angle glaucoma
- Clinically significant abnormal ECG
- Positive Hepatitis B antigen or positive Hepatitis C antibody
- Positive screening test for HIV antibodies
- Current evidence or history of excessive use or abuse of alcohol in the opinion of the Investigator
- Current evidence or history of abusing legal drugs or use of illegal drugs or substances in the opinion of the Investigator
- Donation of 450 ml or more of blood within eight weeks of the Screening Visit
- History of hypersensitivity or intolerance to aerosol medications
- Participation in another investigational drug study where drug was received within 30 days prior to the Screening Visit.
- Inability to comply with study procedures or with study treatment intake, including inability to be trained and/or inability to demonstrate good inhaler technique with Vitalograph AIM
Sites / Locations
- Medicines Evaluation Unit
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm Type
Experimental
Experimental
Experimental
Experimental
Placebo Comparator
Arm Label
glycopyrronium bromide 12.5mcg
glycopyrronium bromide 25mcg
glycopyrronium bromide 50mcg
glycopyrronium bromide 100mcg
placebo
Arm Description
glycopyrronium bromide 12.5mcg single dose via pressurised metered dose inhaler (pMDI)
glycopyrronium bromide 25mcg single dose via pressurised metered dose inhaler (pMDI)
glycopyrronium bromide 50mcg single dose via pressurised metered dose inhaler (pMDI)
glycopyrronium bromide 100mcg single dose via pressurised metered dose inhaler (pMDI)
placebo single dose via pressurised metered dose inhaler (pMDI)
Outcomes
Primary Outcome Measures
Forced Expiratory Volume in one second (FEV1) Area Under the Curve (AUC)
FEV1 time-adjusted AUC(0-24 hours)
Secondary Outcome Measures
Forced Expiratory Volume in one second (FEV1) Area Under the Curve (AUC)
FEV1 time-adjusted AUC(0-12 hours)
Forced Expiratory Volume in one second (FEV1) Area Under the Curve (AUC)
FEV1 time-adjusted AUC(12-24 hours)
Forced Expiratory Volume in one second (FEV1)
Serial FEV1 time-point assessments
Forced Vital Capacity (FVC) Area Under the Curve (AUC)
FVC time-adjusted AUC(0-24 hours), AUC(0-12 hours), AUC(12-24 hours), serial time-point assessment
Forced Expiratory Volume in one second (FEV1) / Forced Vital Capacity (FVC) ratio
Serial FEV1/FVC time-point assessment
Number of subjects reporting adverse events after each treatment as a measure of safety and tolerability
Adverse event monitoring will begin once a subject provides informed consent and will continue until study participation is concluded; incidence rates will be summarised by system organ class, preferred term, severity and by reported relationship to study drug for each treatment
Systolic blood pressure
Descriptive statistics will be presented for the serial measurements by treatment
Diastolic blood pressure
Descriptive statistics will be presented for the serial measurements by treatment
Peripheral pulse rate
Descriptive statistics will be presented for the serial measurements by treatment
Electrocardiography (ECG)
Descriptive statistics will be presented for the serial measurements of each of the standard electrocardiographic (12-lead) parameters by treatment
Clinical hematology
Clinical hematology measures will be taken at the Screening Visit and at the Safety Follow-up Visit and will consist of: red blood cell count, hemoglobin, hematocrit, mean cell hemoglobin, mean cell hemoglobin concentration, mean cell volume, white blood cell count, differential white blood cell count and platelet count. Data will be summarised using descriptive statistics
Clinical chemistry
Clinical chemistry measures will be taken at the Screening Visit and at the Safety Follow-up Visit and will consist of: sodium, potassium, urea, creatinine, uric acid, glucose, calcium, inorganic phosphorus, total bilirubin, alkaline phosphatase, alanine transaminase, aspartate transminase, gamma glutamyl transferase, creatine kinase, total protein, albumin, cholesterol and triglycerides. Data will be summarised using descriptive statistics
Plasma glycopyrronium bromide concentration-time Area Under the Curve (AUC)
AUC (0-infinity) will be extrapolated from serial measures taken over time zero to 24-hours. The descriptive statistics presented by treatment will be: minimum, median, maximum, geometric mean, arithmetic mean and arithmetic standard deviation
Plasma glycopyrronium bromide peak concentration (Cmax)
Cmax will be obtained from serial measures taken over time zero to 24-hours. The descriptive statistics presented by treatment will be: minimum, median, maximum, geometric mean, arithmetic mean and arithmetic standard deviation
Plasma glycopyrronium bromide time to maximum concentration (tmax)
tmax will be calculated from serial measures taken over time zero to 24-hours. The descriptive statistics presented by treatment will be: minimum, median, maximum, geometric mean, arithmetic mean and arithmetic standard deviation
Plasma glycopyrronium bromide concentration elimination half-life (t1/2)
t1/2 will be calculated from serial measures taken over time zero to 24-hours. The descriptive statistics presented by treatment will be: minimum, median, maximum, geometric mean, arithmetic mean and arithmetic standard deviation
Glycopyrronium bromide total plasma clearance following extravascular administration (CL/F)
CL/F will be calculated from serial plasma concentration measures taken over time zero to 24-hours. The descriptive statistics presented by treatment will be: minimum, median, maximum, geometric mean, arithmetic mean and arithmetic standard deviation
Glycopyrronium bromide apparent volume of distribution following extravascular administration (Vz/F)
Vz/F will be calculated from serial plasma concentration measures taken over time zero to 24-hours. The descriptive statistics presented by treatment will be: minimum, median, maximum, geometric mean, arithmetic mean and arithmetic standard deviation
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01703624
Brief Title
Dose Ranging Study of Glycopyrronium Bromide in Patients With Moderate or Severe Chronic Obstructive Pulmonary Disease
Official Title
An Investigation of the Efficacy, Tolerability and Safety of a Range of Doses of Orally Inhaled Glycopyrronium Bromide (PSX1002-GB pMDI) in Male and Female Patients With Moderate or Severe Chronic Obstructive Pulmonary Disease
Study Type
Interventional
2. Study Status
Record Verification Date
March 2016
Overall Recruitment Status
Completed
Study Start Date
May 2013 (undefined)
Primary Completion Date
August 2013 (Actual)
Study Completion Date
September 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Prosonix Limited
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
This is an investigation of the beneficial effects, tolerability and safety of a range of single doses of orally inhaled glycopyrronium bromide (PSX1002GB pMDI) in male and female patients with moderate or severe chronic obstructive pulmonary disease (COPD). COPD is a long term and progressive disease of the lungs, generally caused by cigarette smoking, but other factors may be involved. Glycopyrronium bromide (GB) appears to be particularly useful in dilating the constricted airways of such patients, with a duration of action variously described as being between 12 and 24 hours.
This study will investigate how well tolerated and safe this medication is at a range of doses. It will also help in the selection of a suitable dose for larger and repeat dose studies, based on measures of lung response. It will also help to determine how often the medication should be given; twice daily, or once daily.
Up to 40 patients will be enrolled into the study, ranging in age from 40 to 75 years of age. Patients will be medically assessed before participation to ensure their suitability. The study will take place in one centre in the UK over five sessions; at each session one dose (2 puffs) of GB or one dose (2 puffs) of placebo will be administered from a simple inhaler device. Neither staff nor patients will know which dose, or if placebo, is being taken. Lung function will be measured for up to 26 hours after the administration of each dose using standard spirometry equipment. Blood samples will be taken over a 24-hour period to check the blood levels of GB. There will be a period of about a week between each dosing session. Patients will be medically reviewed after the study to confirm that no untoward effects are present.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Obstructive Pulmonary Disease
Keywords
glycopyrronium bromide, glycopyrrolate, oral inhalation, COPD, chronic obstructive pulmonary disease, lung function, pharmacokinetics, tolerability, safety, cross-over, single-dose, dose-ranging
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
37 (Actual)
8. Arms, Groups, and Interventions
Arm Title
glycopyrronium bromide 12.5mcg
Arm Type
Experimental
Arm Description
glycopyrronium bromide 12.5mcg single dose via pressurised metered dose inhaler (pMDI)
Arm Title
glycopyrronium bromide 25mcg
Arm Type
Experimental
Arm Description
glycopyrronium bromide 25mcg single dose via pressurised metered dose inhaler (pMDI)
Arm Title
glycopyrronium bromide 50mcg
Arm Type
Experimental
Arm Description
glycopyrronium bromide 50mcg single dose via pressurised metered dose inhaler (pMDI)
Arm Title
glycopyrronium bromide 100mcg
Arm Type
Experimental
Arm Description
glycopyrronium bromide 100mcg single dose via pressurised metered dose inhaler (pMDI)
Arm Title
placebo
Arm Type
Placebo Comparator
Arm Description
placebo single dose via pressurised metered dose inhaler (pMDI)
Intervention Type
Drug
Intervention Name(s)
glycopyrronium bromide
Other Intervention Name(s)
PSX1002-GB
Intervention Description
glycopyrronium bromide suspension in HFA
Primary Outcome Measure Information:
Title
Forced Expiratory Volume in one second (FEV1) Area Under the Curve (AUC)
Description
FEV1 time-adjusted AUC(0-24 hours)
Time Frame
From time zero to 24-hours
Secondary Outcome Measure Information:
Title
Forced Expiratory Volume in one second (FEV1) Area Under the Curve (AUC)
Description
FEV1 time-adjusted AUC(0-12 hours)
Time Frame
From time zero to 12-hours
Title
Forced Expiratory Volume in one second (FEV1) Area Under the Curve (AUC)
Description
FEV1 time-adjusted AUC(12-24 hours)
Time Frame
From 12 to 24-hours
Title
Forced Expiratory Volume in one second (FEV1)
Description
Serial FEV1 time-point assessments
Time Frame
From time zero to 24-hours
Title
Forced Vital Capacity (FVC) Area Under the Curve (AUC)
Description
FVC time-adjusted AUC(0-24 hours), AUC(0-12 hours), AUC(12-24 hours), serial time-point assessment
Time Frame
From time zero to 24-hours
Title
Forced Expiratory Volume in one second (FEV1) / Forced Vital Capacity (FVC) ratio
Description
Serial FEV1/FVC time-point assessment
Time Frame
From time zero to 24-hours
Title
Number of subjects reporting adverse events after each treatment as a measure of safety and tolerability
Description
Adverse event monitoring will begin once a subject provides informed consent and will continue until study participation is concluded; incidence rates will be summarised by system organ class, preferred term, severity and by reported relationship to study drug for each treatment
Time Frame
An average of 9 weeks
Title
Systolic blood pressure
Description
Descriptive statistics will be presented for the serial measurements by treatment
Time Frame
From time zero to 24-hours
Title
Diastolic blood pressure
Description
Descriptive statistics will be presented for the serial measurements by treatment
Time Frame
From time zero to 24-hours
Title
Peripheral pulse rate
Description
Descriptive statistics will be presented for the serial measurements by treatment
Time Frame
From time zero to 24-hours
Title
Electrocardiography (ECG)
Description
Descriptive statistics will be presented for the serial measurements of each of the standard electrocardiographic (12-lead) parameters by treatment
Time Frame
From time zero to 24-hours
Title
Clinical hematology
Description
Clinical hematology measures will be taken at the Screening Visit and at the Safety Follow-up Visit and will consist of: red blood cell count, hemoglobin, hematocrit, mean cell hemoglobin, mean cell hemoglobin concentration, mean cell volume, white blood cell count, differential white blood cell count and platelet count. Data will be summarised using descriptive statistics
Time Frame
An average of 9 weeks
Title
Clinical chemistry
Description
Clinical chemistry measures will be taken at the Screening Visit and at the Safety Follow-up Visit and will consist of: sodium, potassium, urea, creatinine, uric acid, glucose, calcium, inorganic phosphorus, total bilirubin, alkaline phosphatase, alanine transaminase, aspartate transminase, gamma glutamyl transferase, creatine kinase, total protein, albumin, cholesterol and triglycerides. Data will be summarised using descriptive statistics
Time Frame
An average of 9 weeks
Title
Plasma glycopyrronium bromide concentration-time Area Under the Curve (AUC)
Description
AUC (0-infinity) will be extrapolated from serial measures taken over time zero to 24-hours. The descriptive statistics presented by treatment will be: minimum, median, maximum, geometric mean, arithmetic mean and arithmetic standard deviation
Time Frame
From time zero to 24-hours
Title
Plasma glycopyrronium bromide peak concentration (Cmax)
Description
Cmax will be obtained from serial measures taken over time zero to 24-hours. The descriptive statistics presented by treatment will be: minimum, median, maximum, geometric mean, arithmetic mean and arithmetic standard deviation
Time Frame
From time zero to 24-hours
Title
Plasma glycopyrronium bromide time to maximum concentration (tmax)
Description
tmax will be calculated from serial measures taken over time zero to 24-hours. The descriptive statistics presented by treatment will be: minimum, median, maximum, geometric mean, arithmetic mean and arithmetic standard deviation
Time Frame
From time zero to 24-hours
Title
Plasma glycopyrronium bromide concentration elimination half-life (t1/2)
Description
t1/2 will be calculated from serial measures taken over time zero to 24-hours. The descriptive statistics presented by treatment will be: minimum, median, maximum, geometric mean, arithmetic mean and arithmetic standard deviation
Time Frame
From time zero to 24-hours
Title
Glycopyrronium bromide total plasma clearance following extravascular administration (CL/F)
Description
CL/F will be calculated from serial plasma concentration measures taken over time zero to 24-hours. The descriptive statistics presented by treatment will be: minimum, median, maximum, geometric mean, arithmetic mean and arithmetic standard deviation
Time Frame
From time zero to 24-hours
Title
Glycopyrronium bromide apparent volume of distribution following extravascular administration (Vz/F)
Description
Vz/F will be calculated from serial plasma concentration measures taken over time zero to 24-hours. The descriptive statistics presented by treatment will be: minimum, median, maximum, geometric mean, arithmetic mean and arithmetic standard deviation
Time Frame
From time zero to 24-hours
10. Eligibility
Sex
All
Minimum Age & Unit of Time
40 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male or female age 40-75 years, inclusive
A clinical diagnosis of moderate to severe COPD (GOLD guidelines)
Current smokers or ex-smokers with at least 10-pack year smoking history
Post-bronchodilator FEV1/FVC ratio < 70 % at Screen
Post-bronchodilator FEV1 ≥ 40 % to < 80 % of predicted at Screen
Demonstrated to be responsive to ipratropium (defined as at least an 100ml increase in FEV1 following ipratropium 80 µg)
Ability to perform acceptable spirometry (ATS/ERS guidelines)
Willing and able to provide written informed consent
Exclusion Criteria:
Females who are pregnant or lactating at the Screening Visit, or if of childbearing potential not using an acceptable means of birth control throughout the study (defined in protocol)
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 (defined in protocol)
Recent history of hospitalisation due to an exacerbation of airway disease within three months prior to the Screening Visit or randomisation
Need for increased treatments of COPD within six weeks prior to the Screening Visit or randomisation
Primary diagnosis of asthma
Prior lung volume reductions surgery or history of chest/lung irradiation
Regular use of daily oxygen therapy
Use of systemic steroids within three months prior to the Screening Visit or during the run-in period
Respiratory tract infection within six weeks prior to the Screening Visit.
History of tuberculosis, bronchiectasis or other non-specific pulmonary disease
History of urinary retention or bladder neck obstructive type symptoms
History of narrow-angle glaucoma
Clinically significant abnormal ECG
Positive Hepatitis B antigen or positive Hepatitis C antibody
Positive screening test for HIV antibodies
Current evidence or history of excessive use or abuse of alcohol in the opinion of the Investigator
Current evidence or history of abusing legal drugs or use of illegal drugs or substances in the opinion of the Investigator
Donation of 450 ml or more of blood within eight weeks of the Screening Visit
History of hypersensitivity or intolerance to aerosol medications
Participation in another investigational drug study where drug was received within 30 days prior to the Screening Visit.
Inability to comply with study procedures or with study treatment intake, including inability to be trained and/or inability to demonstrate good inhaler technique with Vitalograph AIM
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Geoff Down, MB BS FFPM
Organizational Affiliation
Prosonix Limited, Oxford, UK
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Dave Singh, MA MD MRCP
Organizational Affiliation
Medicines Evaluation Unit, Manchester, UK
Official's Role
Principal Investigator
Facility Information:
Facility Name
Medicines Evaluation Unit
City
Manchester
ZIP/Postal Code
M23 9QZ
Country
United Kingdom
12. IPD Sharing Statement
Learn more about this trial
Dose Ranging Study of Glycopyrronium Bromide in Patients With Moderate or Severe Chronic Obstructive Pulmonary Disease
We'll reach out to this number within 24 hrs