Clinical trial NCT00381667: Study to Assess GW642444 in Asthma Patients
Official title: 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 Âµg) of GW642444M
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Pulmonary Disease, Chronic Obstructive
Keywords: safety
GW642444M
Single Dose
pharmacodynamics
pharmacokinetics
GW642444H
tolerability
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2006-09-28
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Adverse events
timeFrame: throughout study
measure: Laboratory safety tests
timeFrame: throughout study
measure: Holter monitoring
timeFrame: throughout study
measure: Vital signs and 12-lead ECG)
timeFrame: throughout study
measure: Mean change from baseline FEV1 24 hours after dosing.
timeFrame: Day 1, on 5 separate occasions
measure: Supine systolic and diastolic blood pressure and supine heart rate
timeFrame: Day 1 on 5 separate occasions
measure: QTc(B)and QTc(F)
timeFrame: Day 1 on 5 separate occasions
Secondary outcomes:
measure: Potassium Max decrease from baseline
timeFrame: Day 1 on 5 separate occasions
measure: Mean change from baseline(0-4h)potassium.
timeFrame: Day 1 on 5 separate occasions
measure: Glucose Max increase from baseline
timeFrame: Day 1 on 5 separate occasions
measure: Weighted mean change from baseline (0-4h)glucose
timeFrame: Day 1 on 5 separate occasions
measure: Derived PK parameters: Cmax, Tmax, AUC(0-t), AUC(0-inf),PEFR
timeFrame: Day 1 on 5 separate occasions
Other outcomes:
Locations:
city: Clayton
country: Australia
facility: GSK Investigational Site
state: Victoria
city: Wellington
country: New Zealand
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: