Study to Assess GW642444 in Asthma Patients

A Randomised, Double-blind, Placebo-controlled, Dose Ascending, Five-way Crossover Study, to Examine Efficacy, Safety, Tolerability, Pharmacodynamics and Pharmacokinetics of a Single Administration of Three Inhaled Doses (25, 100 and 400 µg) of GW642444M

This is a study of GW642444M, a long-acting beta 2 specific agonist. This study will examine GW642444M via the inhaled route and will assess the efficacy, safety, tolerability, pharmacodynamics and pharmacokinetics of a single administration of three inhaled doses (25, 100 and 400 µg) of GW642444M in persistent asthmatics. This study will be a single-centre, placebo-controlled, dose-ascending, five-way crossover in 30 asthmatic patients.

Key assessments: efficacy, safety, tolerability, pharmacokinetics and pharmacodynamics will be assessed by measurement of FEV1, blood pressure, pulse rate, 12-lead ECGs, clinical laboratory safety tests, collection of adverse events and blood samples.

Study Overview

• Status: Completed
• Conditions: Pulmonary Disease, Chronic Obstructive
• Intervention / Treatment: Other: placebo; Drug: GW642444M; Drug: GW642444H

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • GSK Investigational Site
• New Zealand
  • Wellington, New Zealand, 6001
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

• Subjects with a documented history of persistent asthma, with the exclusion of other significant pulmonary diseases
• Female subjects of non-child bearing potential (i.e. post-menopausal or surgically sterile)
• Subjects who are current non-smokers, who have not used any inhaled tobacco products (snuff is permitted) in the 12 month period preceding the screening visit and who have a pack history of less than 10 pack years.
• Subjects with clinically stable persistent asthma within the 4 weeks preceding the screening visit and with a screening pre-bronchodilator FEV1 between 60 and 90% predicted (having abstained from bronchodilators for the required period). Predicted values are based on the ECCS 1993 normal ranges
• During the screening visit, subjects must demonstrate the presence of reversible airway disease, defined as an increase in FEV1 of greater than 12.0% over baseline and an absolute change of greater than 300 mL within 30 minutes following a single 400 mcg salbutamol dose.
• Subjects who are currently taking ICS at a total daily dose of 200 to 500 mcg of FP or equivalent ICS

Exclusion criteria:

• Subjects who have a past or present disease, which as judged by the Investigator and the Medical Monitor, which may affect the safety of the subject or outcome of this study
• A screening Holter ECG tracing that reveals clinically concerning arrhythmias (including, but not limited to, ventricular ectopic runs of 4 beats, R on T phenomena, bigeminy, trigeminy).
• A mean QTc(B) value at screening >430 msec (male) / >450 msec (female) or an ECG that is not suitable for QT measurements (e.g. poorly defined termination of the T wave).
• Any adverse reaction including immediate or delayed hypersensitivity to any ß2 agonist or sympathomimetic drug, or known or suspected sensitivity to the constituents of GW642444 inhalation powder (e.g., lactose or COA).
• Subjects weighing < 50 kg
• Subjects who have participated in any GSK study involving administration of COA.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Placebo	Other: placebo; placebo
Experimental: GW642444M 100mcg	Drug: GW642444M; M salt; Other Names: GW642444
Experimental: GW642444H 100mcg	Drug: GW642444H; H salt
Experimental: GW642444M 12.5	Drug: GW642444M; M salt; Other Names: GW642444
Experimental: GW642444M 400mcg	Drug: GW642444M; M salt; Other Names: GW642444

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Adverse events	throughout study
Laboratory safety tests	throughout study
Holter monitoring	throughout study
Vital signs and 12-lead ECG)	throughout study
Mean change from baseline FEV1 24 hours after dosing.	Day 1, on 5 separate occasions
Supine systolic and diastolic blood pressure and supine heart rate	Day 1 on 5 separate occasions
QTc(B)and QTc(F)	Day 1 on 5 separate occasions

Secondary Outcome Measures

Outcome Measure	Time Frame
Potassium Max decrease from baseline	Day 1 on 5 separate occasions
Mean change from baseline(0-4h)potassium.	Day 1 on 5 separate occasions
Glucose Max increase from baseline	Day 1 on 5 separate occasions
Weighted mean change from baseline (0-4h)glucose	Day 1 on 5 separate occasions
Derived PK parameters: Cmax, Tmax, AUC(0-t), AUC(0-inf),PEFR	Day 1 on 5 separate occasions

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 1, 2006
• Primary Completion (Actual): January 1, 2007
• Study Completion (Actual): January 1, 2007

Study Registration Dates

• First Submitted: September 26, 2006
• First Submitted That Met QC Criteria: September 26, 2006
• First Posted (Estimate): September 28, 2006

Study Record Updates

• Last Update Posted (Estimate): October 28, 2016
• Last Update Submitted That Met QC Criteria: October 26, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Keywords: tolerability; safety; pharmacokinetics; pharmacodynamics; Single Dose; GW642444M; GW642444H
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: B2C104604

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. Clinical Study Report
   Information identifier: B2C104604
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Statistical Analysis Plan
   Information identifier: B2C104604
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Annotated Case Report Form
   Information identifier: B2C104604
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Individual Participant Data Set
   Information identifier: B2C104604
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Informed Consent Form
   Information identifier: B2C104604
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Dataset Specification
   Information identifier: B2C104604
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Study Protocol
   Information identifier: B2C104604
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register