Chronic Obstructive Pulmonary DiseasePhase 2NCT01703624
Dose Ranging Study of Glycopyrronium Bromide in Patients With Moderate or Severe Chronic Obstructive Pulmonary Disease
A Phase 2 study testing glycopyrronium bromide in people with Chronic Obstructive Pulmonary Disease, run by Prosonix Limited at 1 site in United Kingdom.
Trial 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). Read more about this study
- Who is it for?
- Ages 40 to 70 years
- Conditions the study is for
- Chronic Obstructive Pulmonary Disease
- What is being tested?
- glycopyrronium bromide
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 37 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- May 2013to Sep 2013
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 21Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
- Conditions
- Chronic Obstructive Pulmonary Disease
- Being tested
- glycopyrronium bromide
- Keywords
- glycopyrronium bromide, glycopyrrolate, oral inhalation, COPD, chronic obstructive pulmonary disease, lung function, pharmacokinetics, tolerability, safety, cross-over, single-dose, dose-ranging
- Medical subject headings
- Pulmonary Disease, Chronic Obstructive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
glycopyrronium bromideDrug
Also called PSX1002-GB
glycopyrronium bromide suspension in HFA
| Study group | Role | What they receive |
|---|---|---|
| glycopyrronium bromide 12.5mcg | Experimental | glycopyrronium bromide 12.5mcg single dose via pressurised metered dose inhaler (pMDI) Receives: Drug: glycopyrronium bromide |
| glycopyrronium bromide 25mcg | Experimental | glycopyrronium bromide 25mcg single dose via pressurised metered dose inhaler (pMDI) Receives: Drug: glycopyrronium bromide |
| glycopyrronium bromide 50mcg | Experimental | glycopyrronium bromide 50mcg single dose via pressurised metered dose inhaler (pMDI) Receives: Drug: glycopyrronium bromide |
| glycopyrronium bromide 100mcg | Experimental | glycopyrronium bromide 100mcg single dose via pressurised metered dose inhaler (pMDI) Receives: Drug: glycopyrronium bromide |
| placebo | Placebo comparator | placebo single dose via pressurised metered dose inhaler (pMDI) Receives: Drug: glycopyrronium bromide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Forced Expiratory Volume in one second (FEV1) Area Under the Curve (AUC)
FEV1 time-adjusted AUC(0-24 hours)
Measured: From time zero to 24-hours
Secondary outcomes (18)
Forced Expiratory Volume in one second (FEV1) Area Under the Curve (AUC)
FEV1 time-adjusted AUC(0-12 hours)
Measured: From time zero to 12-hours
Forced Expiratory Volume in one second (FEV1) Area Under the Curve (AUC)
FEV1 time-adjusted AUC(12-24 hours)
Measured: From 12 to 24-hours
Forced Expiratory Volume in one second (FEV1)
Serial FEV1 time-point assessments
Measured: From time zero to 24-hours
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
Measured: From time zero to 24-hours
Forced Expiratory Volume in one second (FEV1) / Forced Vital Capacity (FVC) ratio
Serial FEV1/FVC time-point assessment
Measured: From time zero to 24-hours
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
Measured: An average of 9 weeks
Systolic blood pressure
Descriptive statistics will be presented for the serial measurements by treatment
Measured: From time zero to 24-hours
Diastolic blood pressure
Descriptive statistics will be presented for the serial measurements by treatment
Measured: From time zero to 24-hours
Peripheral pulse rate
Descriptive statistics will be presented for the serial measurements by treatment
Measured: From time zero to 24-hours
Electrocardiography (ECG)
Descriptive statistics will be presented for the serial measurements of each of the standard electrocardiographic (12-lead) parameters by treatment
Measured: From time zero to 24-hours
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
Measured: An average of 9 weeks
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
Measured: An average of 9 weeks
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
Measured: From time zero to 24-hours
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
Measured: From time zero to 24-hours
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
Measured: From time zero to 24-hours
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
Measured: From time zero to 24-hours
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
Measured: From time zero to 24-hours
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
Measured: From time zero to 24-hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Oct 2012 (estimated)
- Study startMay 2013
- Primary completionAug 2013
- Study completionSep 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Obstructive Pulmonary DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 37 participants (actual)
Sponsor and investigators
- Lead sponsor
- Prosonix Limited
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Geoff Down, MB BS FFPM, Study director, Prosonix Limited, Oxford, UKDave Singh, MA MD MRCP, Principal investigator, Medicines Evaluation Unit, Manchester, UK
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01703624
- Sponsor's protocol ID
- PSX100201
- Other IDs
- 2012-003791-40
- Status last verified
- Mar 2016
- First submitted
- 4 Oct 2012
- Last updated
- 30 Mar 2016
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Mar 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01703624
- Acronym / sponsor ID
- PSX100201
- Conditions
- Chronic Obstructive Pulmonary Disease
- Keywords
- glycopyrronium bromide, glycopyrrolate, oral inhalation, COPD, chronic obstructive pulmonary disease, lung function, pharmacokinetics, tolerability
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 37 participants (actual)
- Lead sponsor
- Prosonix LimitedIndustry (pharma, biotech, devices)
- Study start
- May 2013
- Primary completion
- Aug 2013 (actual)
- Study completion
- Sep 2013 (actual)
- First posted
- 10 Oct 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| glycopyrronium bromide 12.5mcg | Experimental | Drug: glycopyrronium bromideglycopyrronium bromide 12.5mcg single dose via pressurised metered dose inhaler (pMDI) |
| glycopyrronium bromide 25mcg | Experimental | Drug: glycopyrronium bromideglycopyrronium bromide 25mcg single dose via pressurised metered dose inhaler (pMDI) |
| glycopyrronium bromide 50mcg | Experimental | Drug: glycopyrronium bromideglycopyrronium bromide 50mcg single dose via pressurised metered dose inhaler (pMDI) |
| glycopyrronium bromide 100mcg | Experimental | Drug: glycopyrronium bromideglycopyrronium bromide 100mcg single dose via pressurised metered dose inhaler (pMDI) |
| placebo | Placebo comparator | Drug: glycopyrronium bromideplacebo single dose via pressurised metered dose inhaler (pMDI) |
Who may qualify
- Ages
- 40 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (21 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| glycopyrronium bromideAlso: PSX1002-GBglycopyrronium bromide suspension in HFA | Drug | glycopyrronium bromide 100mcg, glycopyrronium bromide 12.5mcg, glycopyrronium bromide 25mcg, glycopyrronium bromide 50mcg, placebo |
Primary outcome
Forced Expiratory Volume in one second (FEV1) Area Under the Curve (AUC)
Time frame: From time zero to 24-hours
FEV1 time-adjusted AUC(0-24 hours)
18 secondary outcomes
Forced Expiratory Volume in one second (FEV1) Area Under the Curve (AUC)
Time frame: From time zero to 12-hours
Forced Expiratory Volume in one second (FEV1) Area Under the Curve (AUC)
Time frame: From 12 to 24-hours
Forced Expiratory Volume in one second (FEV1)
Time frame: From time zero to 24-hours
Forced Vital Capacity (FVC) Area Under the Curve (AUC)
Time frame: From time zero to 24-hours
Forced Expiratory Volume in one second (FEV1) / Forced Vital Capacity (FVC) ratio
Time frame: From time zero to 24-hours
Number of subjects reporting adverse events after each treatment as a measure of safety and tolerability
Time frame: An average of 9 weeks
Systolic blood pressure
Time frame: From time zero to 24-hours
Diastolic blood pressure
Time frame: From time zero to 24-hours
Peripheral pulse rate
Time frame: From time zero to 24-hours
Electrocardiography (ECG)
Time frame: From time zero to 24-hours
Clinical hematology
Time frame: An average of 9 weeks
Clinical chemistry
Time frame: An average of 9 weeks
Plasma glycopyrronium bromide concentration-time Area Under the Curve (AUC)
Time frame: From time zero to 24-hours
Plasma glycopyrronium bromide peak concentration (Cmax)
Time frame: From time zero to 24-hours
Plasma glycopyrronium bromide time to maximum concentration (tmax)
Time frame: From time zero to 24-hours
Plasma glycopyrronium bromide concentration elimination half-life (t1/2)
Time frame: From time zero to 24-hours
Glycopyrronium bromide total plasma clearance following extravascular administration (CL/F)
Time frame: From time zero to 24-hours
Glycopyrronium bromide apparent volume of distribution following extravascular administration (Vz/F)
Time frame: From time zero to 24-hours
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Mar 2016.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Geoff Down, MB BS FFPM study director
Prosonix Limited, Oxford, UK
Dave Singh, MA MD MRCP principal investigator
Medicines Evaluation Unit, Manchester, UK
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing glycopyrronium bromide in people with Chronic Obstructive Pulmonary Disease, run by Prosonix Limited at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Mar 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Forced Expiratory Volume in one second (FEV1) Area Under the Curve (AUC) (time frame: From time zero to 24-hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Mar 2016.