Safety And Tolerability Study In Patients With Chronic Obstructive Pulmonary Disease

A Randomised, Double-Blind, Placebo-Controlled, Dose Ascending, 3 Period Crossover Study To Examine The Safety, Tolerability, Pharmacodynamics And Pharmacokinetics Of Repeat Inhaled Doses Of GSK233705B In COPD Subjects.

GSK233705 is a high-affinity specific muscarinic receptor (mAChR) antagonist which is being developed for once daily treatment of chronic obstructive pulmonary disease (COPD). The long duration of action of GSK233705 when administered via inhalation in animal models supports the potential for use as a once-daily bronchodilator for chronic obstructive pulmonary disease.

Study Overview

• Status: Completed
• Conditions: Pulmonary Disease, Chronic Obstructive
• Intervention / Treatment: Drug: GSK233705

• Study Type: Interventional
• Enrollment: 45
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Antwerpen, Belgium, 2060
    • GSK Investigational Site
  • Leuven, Belgium, 3000
    • GSK Investigational Site
  • Liège, Belgium, 4000
    • GSK Investigational Site
• Sweden
  • Göteborg, Sweden, SE-413 45
    • GSK Investigational Site
  • Lund, Sweden, SE-221 85
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Female subjects must be of non-childbearing potential including pre-menopausal females
• Male subjects must agree to abstain from or use a condom during sexual intercourse with pregnant or lactating females
• Subject diagnosed with COPD, as defined by the GOLD guidelines
• Body weight greater than 50kg
• Subject is a smoker or an ex-smoker with a smoking history of at least 10 pack years (1 pack year = 20 cigarettes smoked per day for 1 year or equivalent).
• Subject has FEV1/FVC < 0.7 post-bronchodilator (salbutamol).
• Subject has FEV1 greater than or equal to 80% of predicted normal for height, age and gender after inhalation of 200 µg salbutamol.
• Response to ipratropium bromide defined as:
• Either: An increase in FEV1 of =12% and =150 mL at 2 h following inhalation of 80 ug of ipratropium bromide at the screening visit
• or: a documented increase in FEV1 of =12% and =150 mL at 2 h following inhalation of 80 ug of ipratropium bromide within 6 months of screening and an increase in FEV1 of >6% and >100ml 2h following inhalation of 80 ug of ipratropium bromide at the screening visit (in order to allow for potential fluctuations in the response to ipratropium bromide in patients known to be responders to ipratropium bromide).
• Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
• Subject is available to complete all study measurements and procedures.

Exclusion Criteria:

• Subjects who have a past or present disease, judged by the Investigator and the Medical Monitor, to affect the outcome of this study.
• The subject has a positive urine drug/ urine alcohol screen.
• History of alcohol/drug abuse or dependence within 12 months of the study:
• The subject has a positive pregnancy test.
• Subject has FEV1 greater than or equal to 40% of predicted after inhalation of salbutamol.
• A positive Hepatitis B or Hepatitis C result within 3 months of screening
• The subject has participated in a clinical trial and has received a drug or a new chemical entity within 30 days
• Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
• Where participation in study would result in donation of blood in excess of 500 mL within a 56 day period
• The subject has donated a unit of blood within 30 days of screening, or, intends to donate during the study.
• Subject has claustrophobia that may be aggravated by entering the plethysmography cabinet.
• The subject has a known allergy or hypersensitivity to ipratropium bromide, tiotropium bromide, atropine and any of its derivatives or milk protein/lactose.
• History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the physician responsible, contraindicates their participation
• Subject is unable to use the DISKUS™ device correctly.
• Subject has prostate hypertrophy or narrow angle glaucoma.
• Use of prescription drugs (with the exception of those allowed in the protocol) and herbal remedies (e.g. St John's Wort) within 48 hours of each treatment period

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Adverse events Blood pressure Heart rate 12-lead ECG Holter monitoring Lead II ECG monitoring Lung function Clinical laboratory safety tests.

Secondary Outcome Measures

Outcome Measure
Forced Expiratory Volume in 1 second (FEV1) Serial specific airways conductance (sGaw), airways resistance (Raw) Rescue medication usage Plasma and urine concentrations of GSK233705 and derived pharmacokinetic parameters

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

Helpful Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Study record dates

Study Major Dates

• Study Start: August 16, 2006
• Study Completion (Actual): April 3, 2007

Study Registration Dates

• First Submitted: September 13, 2006
• First Submitted That Met QC Criteria: September 13, 2006
• First Posted (Estimate): September 15, 2006

Study Record Updates

• Last Update Posted (Actual): June 7, 2018
• Last Update Submitted That Met QC Criteria: June 5, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Keywords: COPD; repeat dosing; muscarinic receptor antagonist; plethysmography
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: AC2105333

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Study Data/Documents

1. Individual Participant Data Set
   Information identifier: AC2105333
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Statistical Analysis Plan
   Information identifier: AC2105333
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Clinical Study Report
   Information identifier: AC2105333
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Dataset Specification
   Information identifier: AC2105333
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Informed Consent Form
   Information identifier: AC2105333
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Study Protocol
   Information identifier: AC2105333
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Annotated Case Report Form
   Information identifier: AC2105333
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register