Last updated: 11/04/2018 05:34:38

Study to Assess GW642444 in Asthma Patients

Request patient level data
GSK study ID
B2C104604
See study documents
Clinicaltrials.gov ID
NCT00381667
See results summary
EudraCT ID
Not applicable
EU CT Number
Not applicable
Trial status
Study complete
Study complete
Overview
Eligibility
Locations
Study documents
Results summary
Plain language summaries
Additional information

Trial overview

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 µg) of GW642444M
Trial description: 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.
Primary purpose:
Treatment
Trial design:
Crossover Assignment
Masking:
Double (Participant, Investigator)
Allocation:
Randomized
Primary outcomes:

Number of participants with adverse events (AEs) and serious adverse events (SAEs)

Timeframe: SAE and AEs were collected from the time of informed consent to up to follow-up (up to 139 days)

Number of participants with abnormal hematology

Timeframe: Pre-dose , Day 1 (treatment period 1, 2, 3, 4 and 5)

Number of participants with abnormal clinical chemistry data

Timeframe: Pre-dose , Day 1 (treatment period 1, 2, 3, 4 and 5)

Number of participants for indicated urinalysis parameters tested by dipstick

Timeframe: Pre-dose , Day 1 (treatment period 1, 2, 3, 4 and 5)

24-hr Holter monitoring

Timeframe: Day 1 and Day 2 for treatment period 1, 2, 3, 4 and 5

Number of participants with abnormal ECG findings

Timeframe: (Pre-dose 1 to 3, 15 minute (m), 30 m, 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, 24 hr) Day 1 of each treatment period

Change from baseline in systolic blood pressure (SBP) and diastolic blood pressure (DBP)

Timeframe: Pre-dose, 15 m, 30 m, 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, 24 hr, Day 1 of each treatment period

Change from baseline in supine heart rate (HR)

Timeframe: 15 m, 30 m, 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, 24 hr) Day 1 of each treatment period

Number of participants with maximum change from baseline QTc (F) and QTc (B) intervals by category

Timeframe: (Pre-dose 1 to 3, 15 m, 30 m, 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, 24 hr) Day 1 of each treatment period

Secondary outcomes:

Mean change from baseline in forced expiratory volume in 1 second (FEV1), at 24 hrs after dosing

Timeframe: Day 1 and Day 2 for treatment period 1, 2, 3, 4 and 5

Maximum change from baseline (0-8 hr) in SBP

Timeframe: Pre-dose (Day 1) and 0 to 8 hr (Day 1) for treatment period 1, 2, 3, 4 and 5

Maximum change from baseline (0-8 hr) in HR

Timeframe: Pre-dose and 0 to 8 hr (Day 1) for treatment period 1, 2, 3, 4 and 5

Weighted mean change from baseline (0-8 hr): SBP and DBP

Timeframe: Pre-dose Day 1 and (0 to 8 hr) Day 1 for treatment period 1, 2, 3, 4 and 5

Weighted mean change from baseline (0-8 hr): HR

Timeframe: Pre-dose (Day 1 ) and 0 to 8 hr (Day 1) for treatment period 1, 2, 3, 4 and 5

Minimum change from baseline (0-8 hr) for DBP

Timeframe: Pre-dose (Day 1) and 0 to 8 hr (Day 1)

Maximum change from baseline (0–4 hr) for potassium

Timeframe: (Pre-dose 1 to 3, 15 m, 30 m, 1 hr, 2 hr, 3 hr, 4 hr) Day 1 of each treatment period

Weighted mean change from baseline (0-4 hr) potassium

Timeframe: (Pre-dose 1 to 3, 15 m, 30 m, 1 hr, 2 hr, 3 hr, 4 hr) Day 1 of each treatment period

Maximum change from baseline (0–4 hr) for glucose

Timeframe: (Pre-dose 1 to 3, 15 m,30 m, 1 hr, 2 hr, 3 hr, 4 hr) Day 1 of each treatment period

Weighted mean change from baseline (0–4 hr) for glucose

Timeframe: (Pre-dose 1 to 3, 15 m, 30 m, 1 hr, 2 hr, 3 hr, 4 hr) Day 1 of each treatment period

Peak expiratory flow rate (PEFR) at individual time points

Timeframe: Pre-dose, 12 hr (Day 1) and 24 hr (Day 2) for treatment period 1, 2, 3, 4 and 5

Maximum observed plasma concentration (Cmax) for GW642444

Timeframe: (Pre-dose, 5 m, 10 m, 15 m, 20 m, 30 m, 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 10 hr, 12 hr) Day 1 and 24 hr of Day 2 of each treatment period

Time to maximum concentration (Tmax) for GW642444

Timeframe: (Pre-dose, 5 m, 10 m, 15 m, 20m, 30 m, 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 10 hr, 12 hr) at Day 1 and 24 hr of Day 2 of each treatment period

Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUC [0-t]) for GW642444

Timeframe: (Pre-dose, 5 m, 10 m, 15 m, 20 m, 30 m, 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 10 hr, 12 hr) at Day 1 and 24 hr of Day 2 of each treatment period

Area Under the Curve From Time Zero to 2 hr (AUC [0 to 2hr ] )for GW642444

Timeframe: (Pre-dose, 5 m, 10 m, 15 m, 20m, 30 m, 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 10 hr, 12 hr) Day 1 and 24 hr of Day 2 of each treatment period

Area Under the Curve from Time Zero Extrapolated to Infinity (AUC [0-inf]) for GW642444

Timeframe: (Pre-dose, 5 m, 10 m, 15 m, 20 m, 30 m, 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 10 hr, 12 hr) Day 1 and 24 hr of Day 2 of each treatment period

Cmax for GI179710 (triphenylacetate)

Timeframe: (Pre-dose, 5 m, 10 m, 15 m, 20m, 30 m, 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 10 hr, 12 hr) Day 1 and 24 hr of Day 2 of each treatment period

Tmax GI179710 (triphenylacetate)

Timeframe: (Pre-dose, 5 m, 10 m, 15 m, 20 m, 30 m, 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 10 hr, 12 hr) Day 1 and 24 hr of Day 2 of each treatment period

AUC (0 to 2 hr) -GI179710 (triphenylacetate)

Timeframe: (Pre-dose, 5 m, 10 m, 15 m, 20m, 30 m, 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 10 hr, 12 hr) Day 1 and 24 hr of Day 2 of each treatment period

AUC (0–t) for GI179710 (triphenylacetate)

Timeframe: (Pre-dose, 5 m, 10 m, 15 m, 20m, 30 m, 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 10 hr, 12 hr) Day 1 and 24 hr of Day 2 of each treatment period

Cmax for GW630200

Timeframe: (Pre-dose, 5 m, 10 m, 15 m, 20m, 30 m, 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 10 hr, 12 hr) Day 1 and 24 hr of Day 2 of each treatment period

Tmax for GW630200

Timeframe: (Pre-dose, 5 m, 10 m, 15 m, 20m, 30 m, 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 10 hr, 12 hr) Day 1 and 24 hr of Day 2 of each treatment period

AUC (0 to 2hr) for GW630200

Timeframe: (Pre-dose, 5 m, 10 m, 15 m, 20m, 30 m, 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 10 hr, 12 hr) Day 1 and 24 hr of Day 2 of each treatment period

AUC (0–t) for GW630200

Timeframe: (Pre-dose, 5 m, 10 m, 15 m, 20m, 30 m, 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 10 hr, 12 hr) Day 1 and 24 hr of Day 2 of each treatment period

Cmax for GSK932009

Timeframe: (Pre-dose, 5 m, 10 m, 15 m, 20m, 30 m, 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 10 hr, 12 hr) Day 1 and 24 hr of Day 2 of each treatment period

Tmax for GSK932009

Timeframe: (Pre-dose, 5 m, 10 m, 15 m, 20m, 30 m, 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 10 hr, 12 hr) Day 1 and 24 hr of Day 2 of each treatment period

PK parameter-AUC (0–t) for GSK932009

Timeframe: (Pre-dose, 5 m, 10 m, 15 m, 20m, 30 m, 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 10 hr, 12 hr) Day 1 and 24 hr of Day 2 of each treatment period

AUC (0 to 2 hr) for GW6302009

Timeframe: (Pre-dose, 5 m, 10 m, 15 m, 20m, 30 m, 1 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 10 hr, 12 hr) Day 1 and 24 hr of Day 2 of each treatment period

Interventions:
  • Drug: GW642444M
  • Drug: GW642444H
  • Other: placebo
    • Enrollment:
    14
    Primary completion date:
    2007-12-01
    Observational study model:
    Not applicable
    Time perspective:
    Not applicable
    Clinical publications:
    Not applicable
    Medical condition
    Pulmonary Disease, Chronic Obstructive
    Product
    vilanterol
    Collaborators
    Not applicable
    Study date(s)
    August 2006 to January 2007
    Type
    Interventional
    Phase
    2

    Participation criteria

    Sex
    Female & Male
    Age
    18 - 70 years
    Accepts healthy volunteers
    No
    • Inclusion criteria:
    • Subjects with a documented history of persistent asthma, with the exclusion of other significant pulmonary diseases
    Inclusion and exclusion criteria
    Inclusion 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.

    Trial location(s)

    Location
    Status
    Contact us
    Contact us
    Location
    GSK Investigational Site
    Clayton, Victoria, Australia, 3168
    Status
    Study Complete
    Contact us
    Location
    GSK Investigational Site
    Wellington, New Zealand, 6001
    Status
    Study Complete
    Contact us

    Study documents

    Clinical study report
    Available language(s): English
    Download document(s)
    Scientific result summary
    Available language(s): English
    Download document(s)

    If you wish to request for full study report, please contact - [email protected]

    Results overview

    Results posted on ClinicalTrials.gov

    Recruitment status
    Study complete
    Actual primary completion date
    2007-12-01
    Actual study completion date
    2007-12-01

    Plain language summaries

    Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.

    Additional information about the trial

    Participate in clinical trial
    Additional information
    Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.
    Click here
    Access to clinical trial data by researchers
    Visit website