An open-label, randomised, single dose, two-way crossover pilot study to determine the relative bioavailability of a fixed dose combination tablet formulation of GSK587323 (16mg candesartan cilexetil/12.5mg hydrochlorothiazide) relative to respective reference dosage Atacand D in healthy adult human subjects under fasting conditions
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 16
- 试验地点
- 1
- 主要终点
- To assess the relative bioavailability of a candidate formulation of candesartan and HCTZ following administration of a FDC of 16mg candesartan cilexetil/12.5mg HCTZ (GSK587323) relative to reference FDC of 16mg candesartan cilexetil/12.5mg HCTZ (Atacand D) in healthy human subjects under fasting conditions.
研究概览
简要总结
This study aims to determine the relative bioavailability of a fixed dose combination (FDC) tablet formulation of GSK587323 (16mg candesartan cilexetil/12.5mg hydrochlorothiazide) relative to the reference product Atacand D (16mg candesartan cilexetil/12.5mg hydrochlorothiazide, Astra Zeneca, Argentina) in healthy adult subjects. This will be an open-label, randomised, single dose, two-way crossover study.
Each subject will participate in both treatment periods and will receive a single oral dose of the FDC of GSK587323 and reference Atacand D. Treatment periods will be separated by a washout period at least 7 days and no greater than 14 days. Blood samples for pharmacokinetic analysis will be taken at regular intervals after dosing. Safety will be assessed by measurement of vital signs (blood pressure, body temperature, respiration rate and pulse rate), clinical laboratory assessments, electrocardiogram measurements and review of adverse events. The study will enrol 16 healthy subjects to ensure that 14 complete the study as planned.
研究设计
- 研究类型
- Ba/be
- 分配方式
- Computer generated randomization
- 盲法
- Open Label
入排标准
- 年龄范围
- 18.00 Year(s) 至 65.00 Year(s)（—）
- 性别
- All
入选标准
- •Male and females aged between 18 and 65 years of age inclusive, at the time of signing the informed consent 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 parameter(s) which is/are not specifically listed in the inclusion or exclusion criteria,outside the reference range for the population being studied may be included only if the Investigator in consultation with the GSK Medical Monitor if required agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
- •Body weight ≥ 50kg and BMI within the range 19 – 24.9kg/m2 (inclusive) Male subjects with female partners of child-bearing potential must agree to use one of the contraception methods This criterion must be followed from the time of the first dose of study medication until the follow-up contact visit Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form ALT, alkaline phosphatase and bilirubin ≤ 1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%) Based on single or averaged QTc of triplicate ECGs obtained over a brief recording period: QTcF < 450 msec.
排除标准
- •Gastrointestinal disease or with gastrointestinal surgical history which can affect the absorption of the investigational drug Any subject with a systolic BP<95mmHg or with a recent history of postural symptoms.
结局指标
主要结局
To assess the relative bioavailability of a candidate formulation of candesartan and HCTZ following administration of a FDC of 16mg candesartan cilexetil/12.5mg HCTZ (GSK587323) relative to reference FDC of 16mg candesartan cilexetil/12.5mg HCTZ (Atacand D) in healthy human subjects under fasting conditions.
时间窗: Twenty-four (24) blood samples (1 x 6 mL)pre-dose (0.00) and at 0.33, 0.67, 1.00, 1.33, 1.67, 2.00, 2.33, 2.67, 3.00, 3.50, 4.00, 4.50, 5.00, 5.50, 6.00, 7.00, 8.00, 10.00, 12.00, 16.00, 24.00, 36.00 and 48.00 hours post-dose
Plasma PK parameters including Cmax, AUC(0-∞) and AUC(0-t) for candesartan cilexetil and HCTZ in
时间窗: Twenty-four (24) blood samples (1 x 6 mL)pre-dose (0.00) and at 0.33, 0.67, 1.00, 1.33, 1.67, 2.00, 2.33, 2.67, 3.00, 3.50, 4.00, 4.50, 5.00, 5.50, 6.00, 7.00, 8.00, 10.00, 12.00, 16.00, 24.00, 36.00 and 48.00 hours post-dose
relevant treatments
时间窗: Twenty-four (24) blood samples (1 x 6 mL)pre-dose (0.00) and at 0.33, 0.67, 1.00, 1.33, 1.67, 2.00, 2.33, 2.67, 3.00, 3.50, 4.00, 4.50, 5.00, 5.50, 6.00, 7.00, 8.00, 10.00, 12.00, 16.00, 24.00, 36.00 and 48.00 hours post-dose
次要结局
- To characterise secondary PK parameters of a candidate FDC tablet formulation of 16mg candesartan cilexetil/12.5mg HCTZ (GSK587323) relative to reference 16mg candesartan cilexetil/12.5mg HCTZ (Atacand D) in healthy human subjects under fasting conditions.(Plasma PK parameters: tmax, %AUCex and t½)