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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT00976144




Registration number
NCT00976144
Ethics application status
Date submitted
3/09/2009
Date registered
14/09/2009
Date last updated
27/06/2017

Titles & IDs
Public title
Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Effects of GSK573719 (LAMA) and GW642444 (LABA)Administered Individually and Concurrently in Healthy Japanese Subjects
Scientific title
A Single Centre, Randomised, Placebo-controlled, Four-way Cross Over Study to Assess the Safety, Tolerability, Pharmacodynamics and Pharmacokinetics of Single Inhaled Doses of GSK573719 and GW642444 as Monotherapies and Concurrently in Healthy Japanese Subjects
Secondary ID [1] 0 0
113208
Universal Trial Number (UTN)
Trial acronym
DB2113208
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Pulmonary Disease, Chronic Obstructive 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Chronic obstructive pulmonary disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - GSK573719

Experimental: GSK573719, GW642444, GSK573719+GW642444, placebo - This is a four-way cross-over study. Subjects, healthy volunteers, will receive a single dose of GSK573719 (500ug), GW642444 (50ug), GSK573719 (500ug)+GW642444 (50ug) administered concurrently, or placebo at each of the four treatment periods. There is a minimum wash-out period of seven days between doses. On enrolment into the study, subjects will be assigned to one of four treatment sequences which are based on a Williams design in accordance with the randomization schedule generated by GSK prior to study start.


Treatment: Drugs: GSK573719
GSK573719 is a long-acting, inhaled, muscarinic receptor antagonist or anticholinergic bronchodilator. GW642444 is a potent and selective long-acting beta-2 agonist. Both are in development for once daily monotherapies for the treatment of COPD. In this study, their effects are investigated following individual and concurrent administration.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
adverse events, cardiac and ECG parameters, vital signs, lung function and clinical laboratory safety assessments
Timepoint [1] 0 0
From dosing to 24hr post-dose
Secondary outcome [1] 0 0
plasma concentrations of GSK573719 and GW642444 and derived pharmacokinetic parameters thereof
Timepoint [1] 0 0
From dosing to 24 hr post-dose

Eligibility
Key inclusion criteria
- Healthy as determined by a responsible and experienced physician, based on a medical
evaluation including medical history, physical examination, laboratory tests and
cardiac monitoring. A subject with a clinical abnormality or laboratory parameters
outside the reference range for the population being studied may be included only if
the Investigator and the GSK Medical Monitor agree that the finding is unlikely to
introduce additional risk factors and will not interfere with the study procedures.

- Japanese ethnic origin defined as having been born in Japan with four ethnic Japanese
grandparents and able to speak Japanese.

- Male or female between 20 and 65 years of age inclusive, at the time of signing the
informed consent.

- A female subject is eligible to participate if she is of non-childbearing potential
defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or
postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a
blood sample with simultaneous follicle stimulating hormone (FSH) > 40 MlU/ml and
estradiol < 40 pg/ml (<140 pmol/L) is confirmatory].

- Male subjects must agree to use one of the contraception methods listed in Section
8.1. This criterion must be followed from the time of the first dose of study
medication until completion of the follow-up visit.

- Body weight > or equal to 45 kg and BMI within the range 18-28 kg/m2 inclusive.

- AST, ALT, alkaline phosphatase and bilirubin < or equal to 1.5xULN (isolated bilirubin
>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).

- Average QTcB or QTcF < 450 msec; or QTc < 480 msec in subjects with Bundle Branch
Block taken from triplicate assessments at screening.

- No clinically active and relevant abnormality on 12-lead ECG or 24h Holter ECG at
screening.

- Normal spirometry (FEV1 = 80% of predicted, FEV1/FVC = 70%).

- Non-smokers (never smoked or not smoking for >6 months with <10 pack years history
(Pack years = (cigarettes per day smoked/20) x number of years smoked))

- A signed and dated written informed consent is obtained from the subject

- The subject is capable of giving informed consent, which includes compliance with the
requirements and restrictions listed in the consent form

- Available to complete the study
Minimum age
20 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
- Any clinically important abnormality identified at the screening medical assessment
(physical examination/medical history), clinical laboratory tests, or ECG (12-lead). A
24hr Holter monitoring recording outside normal limits.

- A history of breathing problems (i.e. history of asthmatic symptomatology, unless
asthma in childhood that has now resolved and no longer requires maintenance therapy
which should not be an exclusion).

- A mean QTc(B) value at screening >450msec, or an ECG that is not suitable for QT
measurements (e.g. LBBB or poorly defined termination of the T wave).

- A history of elevated resting blood pressure or a mean blood pressure higher than
140/90 mmHg at screening.

- A mean heart rate outside the range 40-90 bpm at screening.

- The subject has a positive pre-study drug/alcohol screen. A minimum list of drugs that
will be screened for include amphetamines, barbiturates, cocaine, opiates and
benzodiazepines. The detection of drugs with a legitimate medical use would not
necessarily be an exclusion to study participation. The detection of alcohol would not
be an exclusion at screening but would need to be negative pre-dose and during the
study.

- A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody
result within 3 months of screening.

- Current or chronic history of liver disease, or known hepatic or biliary abnormalities
(with the exception of Gilbert's syndrome).

- A positive test for HIV antibody.

- History of regular alcohol consumption within 3months of the study defined as:

an average weekly intake of greater than 21 units or an average daily intake of greater
than 3 units (males), or defined as an average weekly intake of greater than 14 units or an
average daily intake of greater than 2 units (females). Under Australian guidelines, one
standard unit defined as 10g of ethanol, is equivalent to 250ml of full-strength beer, 470
ml of light-strength beer, 100 ml of wine and 30ml of spirits.

- The subject has participated in a clinical trial and has received an investigational
product within the following time period prior to the first dosing day in the current
study: 30 days, 5 half-lives or twice the duration of the biological effect of the
investigational product (whichever is longer).

- Exposure to more than four new chemical entities within 12 months prior to the first
dosing day.

- Use of prescription or non-prescription drugs, including vitamins, herbal and dietary
supplements (including St John's Wort) within 7 days (or 14 days if the drug is a
potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first
dose of study medication, unless in the opinion of the Investigator and GSK Medical
Monitor the medication will not interfere with the study procedures or compromise
subject safety.

- History of sensitivity to any of the study medications, or components thereof or a
history of drug or other allergy that, in the opinion of the investigator or GSK
Medical Monitor, contraindicates their participation.

- Where participation in the study would result in donation of blood or blood products
in excess of 500 mL within a 56 day period.

- Unwillingness or inability to follow the procedures outlined in the protocol. 17.
Urinary cotinine levels indicative of smoking or history of regular use of tobacco- or
nicotine-containing products prior to screening.

- The subject is unable to use the novel dry powder inhaler correctly.

- The subject has a known allergy or hypersensitivity to ipratropium bromide,
tiotropium, atropine and any of its derivatives.

- Any adverse reaction including immediate or delayed hypersensitivity to any ß2 agonist
or sympathomimetic drug.

- The subject has a known allergy or hypersensitivity to milk protein or the excipients
lactose monohydrate and MgSt.

- Subject is kept under regulatory of judicial order in an institution.

- Any female of childbearing potential.

- Subject is mentally or legally incapacitated.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Crossover
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
29/07/2009
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
22/09/2009
Sample size
Target
Accrual to date
Final
16
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
GSK Investigational Site - Randwick
Recruitment postcode(s) [1] 0 0
2031 - Randwick

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
GlaxoSmithKline
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
GW642444 is a potent and selective long-acting beta2 agonist; GSK573719 is a long-acting,
inhaled, muscarinic receptor antagonist (or anticholinergic) bronchodilator. Both are in
development as once daily (QD) monotherapies for the treatment of Chronic Obstructive
Pulmonary Disease (COPD). Development of these two inhaled drugs as a combination therapy is
also planned and would have potential for improved efficacy and patient benefit as they both
work through different receptor pathways and the combined bronchodilatory effect might be
additive.

This study is a randomised, double blind, placebo-controlled, four-way crossover study which
will assess the safety, tolerability, pharmacodynamics (PD) and pharmacokinetics (PK) of
GSK573719 and GW642444 in sixteen healthy Japanese subjects. Subjects will receive four
possible treatments as single inhaled doses, receiving the two monotherapies separately, the
monotherapies concurrently, and placebo.

Blood samples for PK analysis will be taken at regular intervals after dosing. Safety will be
assessed by measurement of heart rate, blood pressure, ECG and twenty-four hour Holter
monitoring, potassium, safety laboratory data and review of adverse events.
Trial website
https://clinicaltrials.gov/ct2/show/NCT00976144
Trial related presentations / publications
Kelleher DL, Mehta RS, Jean-Francois BM, Preece AF, Blowers J, Crater GD, Thomas P. Safety, tolerability, pharmacodynamics and pharmacokinetics of umeclidinium and vilanterol alone and in combination: a randomized crossover trial. PLoS One. 2012;7(12):e50716. doi: 10.1371/journal.pone.0050716. Epub 2012 Dec 17.
Public notes

Contacts
Principal investigator
Name 0 0
GSK Clinical Trials
Address 0 0
GlaxoSmithKline
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT00976144