Dose Ranging Study of Glycopyrronium Bromide in Patients With Moderate or Severe Chronic Obstructive Pulmonary Disease

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Prosonix Limited
ClinicalTrials.gov Identifier:
NCT01703624
First received: October 4, 2012
Last updated: October 17, 2013
Last verified: October 2013
  Purpose

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.


Condition Intervention Phase
Chronic Obstructive Pulmonary Disease
Drug: glycopyrronium bromide
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Prosonix Limited:

Primary Outcome Measures:
  • Forced Expiratory Volume in one second (FEV1) Area Under the Curve (AUC) [ Time Frame: From time zero to 24-hours ] [ Designated as safety issue: No ]
    FEV1 time-adjusted AUC(0-24 hours)


Secondary Outcome Measures:
  • Forced Expiratory Volume in one second (FEV1) Area Under the Curve (AUC) [ Time Frame: From time zero to 12-hours ] [ Designated as safety issue: No ]
    FEV1 time-adjusted AUC(0-12 hours)

  • Forced Expiratory Volume in one second (FEV1) Area Under the Curve (AUC) [ Time Frame: From 12 to 24-hours ] [ Designated as safety issue: No ]
    FEV1 time-adjusted AUC(12-24 hours)

  • Forced Expiratory Volume in one second (FEV1) [ Time Frame: From time zero to 24-hours ] [ Designated as safety issue: No ]
    Serial FEV1 time-point assessments

  • Forced Vital Capacity (FVC) Area Under the Curve (AUC) [ Time Frame: From time zero to 24-hours ] [ Designated as safety issue: No ]
    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 [ Time Frame: From time zero to 24-hours ] [ Designated as safety issue: No ]
    Serial FEV1/FVC time-point assessment

  • Number of subjects reporting adverse events after each treatment as a measure of safety and tolerability [ Time Frame: An average of 9 weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: From time zero to 24-hours ] [ Designated as safety issue: No ]
    Descriptive statistics will be presented for the serial measurements by treatment

  • Diastolic blood pressure [ Time Frame: From time zero to 24-hours ] [ Designated as safety issue: No ]
    Descriptive statistics will be presented for the serial measurements by treatment

  • Peripheral pulse rate [ Time Frame: From time zero to 24-hours ] [ Designated as safety issue: No ]
    Descriptive statistics will be presented for the serial measurements by treatment

  • Electrocardiography (ECG) [ Time Frame: From time zero to 24-hours ] [ Designated as safety issue: No ]
    Descriptive statistics will be presented for the serial measurements of each of the standard electrocardiographic (12-lead) parameters by treatment

  • Clinical hematology [ Time Frame: An average of 9 weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: An average of 9 weeks ] [ Designated as safety issue: No ]
    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) [ Time Frame: From time zero to 24-hours ] [ Designated as safety issue: No ]
    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) [ Time Frame: From time zero to 24-hours ] [ Designated as safety issue: No ]
    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) [ Time Frame: From time zero to 24-hours ] [ Designated as safety issue: No ]
    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) [ Time Frame: From time zero to 24-hours ] [ Designated as safety issue: No ]
    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) [ Time Frame: From time zero to 24-hours ] [ Designated as safety issue: No ]
    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) [ Time Frame: From time zero to 24-hours ] [ Designated as safety issue: No ]
    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


Enrollment: 37
Study Start Date: May 2013
Study Completion Date: September 2013
Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: glycopyrronium bromide 12.5mcg
glycopyrronium bromide 12.5mcg single dose via pressurised metered dose inhaler (pMDI)
Drug: glycopyrronium bromide
glycopyrronium bromide suspension in HFA
Other Name: PSX1002-GB
Experimental: glycopyrronium bromide 25mcg
glycopyrronium bromide 25mcg single dose via pressurised metered dose inhaler (pMDI)
Drug: glycopyrronium bromide
glycopyrronium bromide suspension in HFA
Other Name: PSX1002-GB
Experimental: glycopyrronium bromide 50mcg
glycopyrronium bromide 50mcg single dose via pressurised metered dose inhaler (pMDI)
Drug: glycopyrronium bromide
glycopyrronium bromide suspension in HFA
Other Name: PSX1002-GB
Experimental: glycopyrronium bromide 100mcg
glycopyrronium bromide 100mcg single dose via pressurised metered dose inhaler (pMDI)
Drug: glycopyrronium bromide
glycopyrronium bromide suspension in HFA
Other Name: PSX1002-GB
Placebo Comparator: placebo
placebo single dose via pressurised metered dose inhaler (pMDI)

  Eligibility

Ages Eligible for Study:   40 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01703624

Locations
United Kingdom
Medicines Evaluation Unit
Manchester, United Kingdom, M23 9QZ
Sponsors and Collaborators
Prosonix Limited
Investigators
Study Director: Geoff Down, MB BS FFPM Prosonix Limited, Oxford, UK
Principal Investigator: Dave Singh, MA MD MRCP Medicines Evaluation Unit, Manchester, UK
  More Information

No publications provided

Responsible Party: Prosonix Limited
ClinicalTrials.gov Identifier: NCT01703624     History of Changes
Other Study ID Numbers: PSX100201, 2012-003791-40
Study First Received: October 4, 2012
Last Updated: October 17, 2013
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
United Kingdom: Research Ethics Committee

Keywords provided by Prosonix Limited:
glycopyrronium bromide
glycopyrrolate
oral inhalation
COPD
chronic obstructive pulmonary disease
lung function
pharmacokinetics
tolerability
safety
cross-over
single-dose
dose-ranging

Additional relevant MeSH terms:
Lung Diseases
Lung Diseases, Obstructive
Pulmonary Disease, Chronic Obstructive
Respiratory Tract Diseases
Bromides
Glycopyrrolate
Anticonvulsants
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Adjuvants, Anesthesia
Muscarinic Antagonists
Cholinergic Antagonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 18, 2014