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

Sponsor

GlaxoSmithKline (Industry)

Overall Status

Completed

CT.gov ID

NCT00475436

Collaborator

(none)

Enrollment

Location

Arm

4.2

Actual Duration (Months)

8.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Pulmonary Disease, Chronic Obstructive	Drug: GSK573719	Phase 1

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 Design

Study Type:

Interventional

Actual Enrollment :

36 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

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.

Actual Study Start Date :

May 14, 2007

Actual Primary Completion Date :

Sep 18, 2007

Actual Study Completion Date :

Sep 18, 2007

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm 1	Drug: GSK573719

Arm

Intervention/Treatment

Experimental: Arm 1

Drug: GSK573719

Outcome Measures

Primary Outcome Measures

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

- 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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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