A Randomised, Double-blind, Placebo-controlled, Four-way Crossover Study to Compare the Pharmacodynamics and Pharmacokinetics of GW685698X and GW642444M When Administered Separately and in Combination as a Single Dose From a Novel Dry Powder Device in Healthy Japanese Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 16
- 试验地点
- 1
- 主要终点
- Blood pressure changes
研究概览
简要总结
A combination of the corticosteroid GW685698X and the long-acting ß2-agonist GW642444M is being developed for once daily administration for the maintenance treatment of asthma and COPD. GW642444M and GW685698X will be simultaneously co-administered from a single device and compared with GW642444M and GW685698X administered separately in order to determine whether co-administration affects the safety, tolerability, pharmacodynamic and/or pharmacokinetics of either compound in healthy Japanese subjects.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
入排标准
- 年龄范围
- 20 Years 至 60 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- 未提供
排除标准
- •As a result of medical interview, physical examination or screening investigations, the principle investigator or delegate physician deems the subject unsuitable for the study. Subjects must not have a systolic blood pressure above 145 mmHg or a diastolic pressure above 85 mmHg unless the Investigator confirms that it is satisfactory for their age.
- •The subject has been treated for or diagnosed with depression within six months of screening or has a history of significant psychiatric illness.
- •Subjects who have suffered an upper or lower respiratory tract infection within 4 weeks of the screening visit.
- •Liver function tests (AST, ALT or ALP) greater than 1.5 of the upper limit of laboratory reference range.
- •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 physician responsible, contraindicates their participation.
- •History of milk protein allergy.
- •The subject has taken 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 the longer) prior to the first dose of study medication, unless in the opinion of the Investigator and Sponsor the medication will not interfere with the study procedures or compromise subject safety.
- •The subject has taken oral corticosteroids less than 8 weeks before the screening visit
- •The subject has taken inhaled, intranasal or topical steroids less than 4 weeks before the screening visit
- •History of alcohol/drug abuse or dependence within 12 months of the study
- •Abuse of alcohol 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 285mL glass of full strength beer or 425mL schooner of light beer or 1 (30mL) measure of spirits or 1 glass (100mL) of wine
- •The subject has participated in a clinical trial and has received a drug or a new chemical entity within 30 days or 5 half-lives, or twice the duration of the biological effect of any drug (whichever is longer) prior to the first dose of current study medication.
- •Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
- •The subject has donated a unit (450mL) of blood within the previous 16 weeks or intends to donate within 16 weeks after completing the study.
- •A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening.
- •The subject has tested positive for HIV antibodies.
- •The subject has a positive pre-study urine drug screen. A minimum list of drugs that will be screened for include amphetamines, barbiturates, cocaine, opiates, cannabinoids and benzodiazepines.
- •Positive CO or alcohol breath test at screening or on admission to the Unit.
- •History of any adverse reaction including immediate or delayed hypersensitivity to any ICS, β2 agonist or sympathomimetic drug.
- •Any known or suspected sensitivity to the constituents of GW642444M or GW685698X inhalation powder (i.e., lactose, magnesium stearate).
- •Subjects at risk of non-compliance.
研究组 & 干预措施
Subjects receiving fluticasone foroate/ vilanterol
Eligible subjects will receive single dose of fluticasone foroate/ vilanterol combination treatment 800 micrograms/ 50 micrograms administered using a novel powder inhaler. There will be a washout period of 7 to 10 days between treatments.
干预措施: Fluticasone foroate/ vilanterol (Drug)
Subjects receiving fluticasone foroate/ vilanterol
Eligible subjects will receive single dose of fluticasone foroate/ vilanterol combination treatment 800 micrograms/ 50 micrograms administered using a novel powder inhaler. There will be a washout period of 7 to 10 days between treatments.
干预措施: Fluticasone foroate (Drug)
Subjects receiving fluticasone foroate/ vilanterol
Eligible subjects will receive single dose of fluticasone foroate/ vilanterol combination treatment 800 micrograms/ 50 micrograms administered using a novel powder inhaler. There will be a washout period of 7 to 10 days between treatments.
干预措施: Vilanterol (Drug)
Subjects receiving fluticasone foroate
Eligible subjects will receive single dose of fluticasone foroate 800 micrograms administered using a novel powder inhaler.
干预措施: Fluticasone foroate (Drug)
Subjects receiving vilanterol
Eligible subjects will receive single dose of vilanterol 50 micrograms administered using a novel powder inhaler.
干预措施: Vilanterol (Drug)
Subjects receiving placebo
Eligible subjects will receive single dose of placebo administered using a novel powder inhaler.
干预措施: Placebo (Drug)
结局指标
主要结局
Blood pressure changes
时间窗: over 12 hours.
Electrocardiogram changes
时间窗: over 12 hours.
Change in peak expiry flow rate changes
时间窗: over 24 hours.
Change in serum cortisol concentration changes
时间窗: over 24 hours
Maximum heart rate
时间窗: over 4 hours after dosing.
次要结局
- Change in plasma drug concentration (AUC, Cmax, t1/2, tmax)(over 48 hours after dosing.)
- Change in blood potassium levels(within 4 hours of drug dosing.)
- Mean heart rate(over 4 hours after dosing)
- Plasma concentrations and derived pharmacokinetic parameters (AUC, Cmax,t½, tmax) for GW685698X, GW642444 and the GW642444 inactive metabolites GW630200 and GSK932009(over 48 hours after dosing)