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 Subjects.
Overview
- Phase
- Phase 1
- Intervention
- GSK233705
- Conditions
- Pulmonary Disease, Chronic Obstructive
- Sponsor
- GlaxoSmithKline
- Enrollment
- 16
- Locations
- 1
- Primary Endpoint
- General safety endpoints: measured over 24 hours post dose for all 4 dose periods, heart rate, systolic and diastolic blood pressure, 12- lead ECG and lung function and clinical laboratory safety tests. Adverse events over whole study.
- 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 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.
- •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
- •Male subjects must agree to use one of the contraception methods listed in protocol. This criterion must be followed from the time of the first dose of study medication until 90 days post-last dose.
- •BMI within the range 18 - 30 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%).
- •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
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 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
Period 1
Subjects will receive first placebo, then GSK233705, GW642444 and combination of GSK233705 and GW642444
Intervention: GSK233705
Period 1
Subjects will receive first placebo, then GSK233705, GW642444 and combination of GSK233705 and GW642444
Intervention: GW642444
Period 1
Subjects will receive first placebo, then GSK233705, GW642444 and combination of GSK233705 and GW642444
Intervention: GSK233705 and GW642444
Period 1
Subjects will receive first placebo, then GSK233705, GW642444 and combination of GSK233705 and GW642444
Intervention: Placebo
Period 2
Subjects will receive first combination of GSK233705 and GW642444, then placebo, GSK233705 and GW642444
Intervention: GSK233705
Period 2
Subjects will receive first combination of GSK233705 and GW642444, then placebo, GSK233705 and GW642444
Intervention: GW642444
Period 2
Subjects will receive first combination of GSK233705 and GW642444, then placebo, GSK233705 and GW642444
Intervention: GSK233705 and GW642444
Period 2
Subjects will receive first combination of GSK233705 and GW642444, then placebo, GSK233705 and GW642444
Intervention: Placebo
Period 3
Subjects will receive first GSK233705, then GW642444, combination of GSK233705 and GW642444 and later placebo
Intervention: GSK233705
Period 3
Subjects will receive first GSK233705, then GW642444, combination of GSK233705 and GW642444 and later placebo
Intervention: GW642444
Period 3
Subjects will receive first GSK233705, then GW642444, combination of GSK233705 and GW642444 and later placebo
Intervention: GSK233705 and GW642444
Period 3
Subjects will receive first GSK233705, then GW642444, combination of GSK233705 and GW642444 and later placebo
Intervention: Placebo
Period 4
Subjects will receive first GW642444, then combination of GSK233705 and GW642444, placebo, and later GSK233705
Intervention: GSK233705
Period 4
Subjects will receive first GW642444, then combination of GSK233705 and GW642444, placebo, and later GSK233705
Intervention: GW642444
Period 4
Subjects will receive first GW642444, then combination of GSK233705 and GW642444, placebo, and later GSK233705
Intervention: GSK233705 and GW642444
Period 4
Subjects will receive first GW642444, then combination of GSK233705 and GW642444, placebo, and later GSK233705
Intervention: Placebo
Outcomes
Primary Outcomes
General safety endpoints: measured over 24 hours post dose for all 4 dose periods, heart rate, systolic and diastolic blood pressure, 12- lead ECG and lung function and clinical laboratory safety tests. Adverse events over whole study.
Time Frame: Up to Day 2
Secondary Outcomes
- Blood levels of GW642444, Blood levels of GSK233705, Blood Levels of potassium(Pre-dose; Day 1- 5, 15 and 30 minutes, 1, 2, 4, 5,6, 8, 12, 16 and 24 hours and Day 2)