A Single Centre Randomized Study Evaluating The Safety And Tolerability Of GSK573719 In Healthy Volunteers

A Single-centre, Randomised, Double-blind, Placebo-controlled, Dose-ascending, 3-cohort Parallel-group Study to Evaluate the Safety, Tolerability, Pharmacodynamics and Pharmacokinetics of GSK573719 Administered as Singledoses (750 μg and 1000 μg) and Repeat Doses Over 14 Days (250 μg-1000 μg Once-daily) of GSK573719 in Healthy Male and Female Subjects.

GSK573719 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 GSK573719 when administered via inhalation in animal models supports the potential for use as a once-daily bronchodilator for COPD

Study Overview

• Status: Completed
• Conditions: Pulmonary Disease, Chronic Obstructive
• Intervention / Treatment: Drug: GSK573719

Detailed Description

A single-centre, randomised, double-blind, placebo-controlled, dose-ascending, 3-cohort parallel-group study to evaluate the safety, tolerability, pharmacodynamics and pharmacokinetics of GSK573719 administered as single doses (750µg and 1000µg) and repeat doses over 14 days (250µg-1000µg once-daily) of GSK573719 in healthy male and female subjects

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 14050
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion criteria:

• Healthy Caucasian male subjects or healthy Caucasian female subjects of non-childbearing potential
• Aged between 18-55 years
• Non-smokers
• Normal spirometry (FEV1 = 80% of predicted, FEV1/FVC = 70%)
• A signed and dated written informed consent is obtained from the subject
• The subject is capable of giving informed consent
• Available to complete the study
• Subject has a BMI within the range 18.0-30.0kg/m2 inclusive

Exclusion criteria:

• Any clinically important abnormality identified at the screening medical assessment
• A history of breathing problems
• A mean QTc(B) value at screening >450msec, the QTc(B) of all 3 screening ECGs are not within 10% of the mean, or an ECG that is not suitable for QT measurements
• A history of elevated resting blood pressure or a mean blood pressure equal to or higher than 140/90 mmHg at screening
• A mean heart rate outside the range 40-90 bpm at screening
• History of use of tobacco products within 6 months of screening, or positive urine cotinine at screening
• Subjects with a 2D6 poor metabolizer genotype (Caucasian)
• The subject has donated a unit (400ml) of blood within 60 days of screening, or, intends to donate during the study
• The subject is currently taking regular (or course of) medication, whether prescribed or not
• The subject has taken prescription medications within the past 2 weeks prior to dosing or OTC medications within 48 hours prior to dosing
• The subject has participated in a study with a new molecular entity or any other trial within a period of 3 months prior to dosing
• The subject has tested positive for hepatitis C antibody, hepatitis B surface antigen or HIV
• The subject has a positive pre-study drug screen
• The subject has a positive pre-study alcohol screen
• The subject has a suspected history of alcohol abuse within the six months previous to the screening visit
• The subject is unable to use the DISKUS
• The subject has a known allergy or hypersensitivity to ipratropium bromide, atropine and any of its derivatives
• The subject has a known allergy or hypersensitivity to milk protein or the excipient lactose monohydrate
• Subjects who might have prostatic hypertrophy, bladder outlet obstruction, or narrow angle glaucoma

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1	Drug: GSK573719

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
General safety and tolerability endpoints: adverse events, blood pressure, heart rate, 12-lead ECG, Holter and Lead II ECG monitoring, lung function and clinical laboratory safety tests throughout the study	throughout the study

Secondary Outcome Measures

Outcome Measure	Time Frame
- Ambulatory blood pressure for repeat dosing - 24hr Holter monitoring for repeat dosing - Plasma and urine concentrations of GSK573719 and derived pharmacokinetic parameters	throughout the study

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Cahn A, Tal-Singer R, Pouliquen IJ, Mehta R, Preece A, Hardes K, Crater G, Deans A. Safety, tolerability, pharmacokinetics and pharmacodynamics of single and repeat inhaled doses of umeclidinium in healthy subjects: two randomized studies. Clin Drug Investig. 2013 Jul;33(7):477-88. doi: 10.1007/s40261-013-0088-7.

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 (Actual): May 14, 2007
• Primary Completion (Actual): September 18, 2007
• Study Completion (Actual): September 18, 2007

Study Registration Dates

• First Submitted: May 16, 2007
• First Submitted That Met QC Criteria: May 16, 2007
• First Posted (Estimate): May 21, 2007

Study Record Updates

• Last Update Posted (Actual): August 4, 2017
• Last Update Submitted That Met QC Criteria: August 2, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Keywords: muscarinic receptor antagonist; chronic obstructive pulmonary disease,; GSK573719,
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: AC4106889

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. Dataset Specification
   Information identifier: AC4106889
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Informed Consent Form
   Information identifier: AC4106889
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Study Protocol
   Information identifier: AC4106889
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Annotated Case Report Form
   Information identifier: AC4106889
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Clinical Study Report
   Information identifier: AC4106889
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Statistical Analysis Plan
   Information identifier: AC4106889
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Individual Participant Data Set
   Information identifier: AC4106889
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register