NCT00783003
Completed
Phase 1
A Single Centre, Randomised, Placebo-controlled, Four-way Cross Over Study to Assess the Safety, Tolerability, Pharmacodynamics and Pharmacokinetics of Single Inhaled Doses of GSK233705 and GW642444 as Monotherapies and in Combination in Healthy Japanese Subjects
ConditionsPulmonary Disease, Chronic Obstructive
Overview
- Phase
- Phase 1
- Intervention
- GSK233705
- Conditions
- Pulmonary Disease, Chronic Obstructive
- Sponsor
- GlaxoSmithKline
- Enrollment
- 16
- Locations
- 1
- Primary Endpoint
- Heart rate
- Status
- Completed
- Last Updated
- 8 years ago
Overview
Brief Summary
GW642444 and GSK233705 are in development for treatment of Chronic Obstructive Pulmonary Disease. Development of these two inhaled drugs as a combination therapy would have potential for improved patient benefit as they both work through different mechanisms and the combined bronchodilatory effect might be additive. This study will look at the this combination, for the first time, in healthy Japanese subjects.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Healthy as determined by a responsible 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 18 and 65 years of age.
- •Female subjects must be of non childbearing potential including pre-menopausal females with documented (medical report verification) hysterectomy or double oophorectomy or postmenopausal defined as 12 months of spontaneous amenorrhea or 6 months of spontaneous amenorrhea with serum FSH levels \> 40 mIU/mL and estradiol \< 40 pg/ml (\<140 pmol/L) or 6 weeks postsurgical bilateral oophorectomy with or without hysterectomy.
- •Male subjects must agree to use one of the contraception methods listed in Section 8.
- •This criterion must be followed from the time of the first dose of study medication until 90 days post-last dose.
- •Body weight \> 45 kg and body mass index within the range of 18-28 kg/m2 inclusive.
- •Average QTc(B) \< 450 msec taken from triplicate assessments at screening.
- •No clinically active and relevant abnormality on 12-lead ECG at screening or 24h Holter ECG.
- •Normal spirometry (FEV1 ≥ 80% of predicted, FEV1/FVC ≥ 70%).
Exclusion Criteria
- •Any clinically important abnormality identified at the screening medical assessment (physical examination/medical history), clinical laboratory tests, or ECG (12-lead). 24hr Holter monitoring 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.
- •A positive test for HIV antibody (if determined by the local SOP's).
- •History of high 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). One unit is equivalent to a half-pint (220mL) of beer or 1 (25ml) measure of spirits or 1 glass (125ml) of wine.
- •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).
Arms & Interventions
Long acting muscarinic receptor antagonist (LAMA)
Inhaled Long acting muscarinic receptor antagonist (LAMA which is in development as a treatment for Chronic Obstructive Pulmonary Disease.
Intervention: GSK233705
Long acting Beta 2 agonist (LABA)
Inhaled Long Acting Beta 2 agonist (LABA) which is in development as a treatment for Chronic Obstructive Pulmonary Disease.
Intervention: GW642444
LAMA with LABA
Inhaled Long Acting Muscarinic receptor Antagonist (LAMA) and a inhaled Long Acting Beta 2 Agonist (LABA), both in development for treatment of Chronic Obstructive Pulmonary Disease and taken in combination.
Intervention: GSK233705 and GW642444
Placebo
Matching placebo, no intervention.
Intervention: Placebo
Outcomes
Primary Outcomes
Heart rate
Time Frame: 24 hours
Systolic and diastolic blood pressure
Time Frame: 24 hours
12 lead ECG
Time Frame: 24 hours
Lung Function
Time Frame: 24 hours
Clinical laboratory safety tests
Time Frame: 24 hours
Adverse events
Time Frame: Duration of study
Secondary Outcomes
- Plasma concentrations of GSK233705 and derived pharmacokinetic parameters.(24 hours)
- Plasma concentrations of GW642444 and derived pharmacokinetic parameters.(24 hours)
- Weighted mean and minimum value potassium(0 to 4 hours post dose)
Study Sites (1)
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