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

NCT01703624 | Completed Phase 2

• 2 other identifiers: PSX1002012012-003791-40
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Forced Expiratory Volume in one second (FEV1) Area Under the Curve (AUC)

  FEV1 time-adjusted AUC(0-24 hours)

  From time zero to 24-hours

Secondary Outcomes (18)

• Forced Expiratory Volume in one second (FEV1) Area Under the Curve (AUC)

  From time zero to 12-hours

• Forced Expiratory Volume in one second (FEV1) Area Under the Curve (AUC)

  From 12 to 24-hours

• Forced Expiratory Volume in one second (FEV1)

  From time zero to 24-hours

• Forced Vital Capacity (FVC) Area Under the Curve (AUC)

  From time zero to 24-hours

• Forced Expiratory Volume in one second (FEV1) / Forced Vital Capacity (FVC) ratio

  From time zero to 24-hours

Study Arms (5)

glycopyrronium bromide 12.5mcg

EXPERIMENTAL

glycopyrronium bromide 12.5mcg single dose via pressurised metered dose inhaler (pMDI)

Drug: glycopyrronium bromide

glycopyrronium bromide 25mcg

EXPERIMENTAL

glycopyrronium bromide 25mcg single dose via pressurised metered dose inhaler (pMDI)

Drug: glycopyrronium bromide

glycopyrronium bromide 50mcg

EXPERIMENTAL

glycopyrronium bromide 50mcg single dose via pressurised metered dose inhaler (pMDI)

Drug: glycopyrronium bromide

glycopyrronium bromide 100mcg

EXPERIMENTAL

glycopyrronium bromide 100mcg single dose via pressurised metered dose inhaler (pMDI)

Drug: glycopyrronium bromide

placebo

PLACEBO COMPARATOR

placebo single dose via pressurised metered dose inhaler (pMDI)

Drug: glycopyrronium bromide

Interventions

glycopyrronium bromide DRUG

glycopyrronium bromide suspension in HFA

Also known as: PSX1002-GB

glycopyrronium bromide 100mcg; glycopyrronium bromide 12.5mcg; glycopyrronium bromide 25mcg; glycopyrronium bromide 50mcg; placebo

Eligibility Criteria

• Age: 40 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Prosonix Limited: lead

Study Sites (1)

Medicines Evaluation Unit

Manchester, M23 9QZ, United Kingdom

Location

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Interventions

Glycopyrrolate

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Quaternary Ammonium Compounds; Amines; Organic Chemicals; Onium Compounds; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Geoff Down, MB BS FFPM

  Prosonix Limited, Oxford, UK

  STUDY DIRECTOR

• Dave Singh, MA MD MRCP

  Medicines Evaluation Unit, Manchester, UK

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 4, 2012
• First Posted: October 10, 2012
• Study Start: May 1, 2013
• Primary Completion: August 1, 2013
• Study Completion: September 1, 2013
• Last Updated: March 30, 2016

Record last verified: 2016-03

Locations

GB (1)