An Open Label, Non-Randomized, Single Dose, Two Period, Cross-Over, Mass Balance Study to Investigate the Recovery, Excretion, and Pharmacokinetics of 14C -GSK1322322 Administered as a Single Intravenous and Single Oral Dose to Healthy Adult Male Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 5
- 试验地点
- 1
- 主要终点
- Percent total recovery of radioactivity in urine and feces in each interval and cumulative
研究概览
简要总结
This is a phase 1, non-randomized, open label, single-dose, two-period, cross-over study. This study will utilize 14C radiolabeled GSK1322322 to investigate the recovery, excretion, and pharmacokinetics of GSK1322322 in 6 healthy adult male subjects through the sampling of blood, urine, and feces.
Each subject will participate in the study for approximately 7 to 8 weeks i.e., 30 day screening period, two dosing periods (approximately 8 days each) and a follow up visit.
The subjects will be admitted to the clinical unit on Day 1 of the first treatment period and remain in the unit for up to approximately 16 days through the end of the second treatment period.
On Day 1 of Period 1, each subject will receive 14C radiolabeled GSK1322322 as a single therapeutic intravenous (IV) dose (1000 milligrams [mg]). When the total radioactivity is <1% of the administered dose in all subjects, Period 2 dosing will begin (approximately 8 days after the IV dose). On Day 1 of Period 2, each subject will receive single therapeutic oral solution dose (1200 mg). Blood, urine, bile and fecal samples will be collected during both the periods. The subject may be discharged from the unit as early as Day 8 of Period 2. Subjects will visit the study unit for the follow-up visit 7 to 10 days following discharge from the unit.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 30 Years 至 55 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Healthy male subjects between 30 and 55 years of age, with body weight between 60 to 80 kilograms (kg) and a history of regular bowel movements
- •Male subjects with female partners of child-bearing potential must agree to use one of the contraception methods from first dose of study medication until the final follow up visit
- •Alanine aminotransferase (ALT), alkaline phosphatase and bilirubin =<1.5x upper limit of normal
- •QT interval by Bazett's correction formula (QTcB) <450 millisecond (msec); or QTcB <480 msec in subjects with Bundle Branch Block
- •Available to complete the study and return for follow-up visits if necessary
- •Capable of giving written informed consent
排除标准
- •Any condition that could interfere with the accurate assessment and recovery of radioactivity [14C]
- •Participation in a clinical trial involving administration of radiolabeled 14C-labelled compound(s) within the last 12 months
- •Any condition which impairs the absorption, distribution, metabolism or excretion of the investigational product
- •Subjects with a history of cholecystectomy
- •Subject has received a total body radiation dose of greater than 5.0 millisievert (mSv) or exposure to significant radiation during 1 year before dosing
- •The subject has a positive: drug/alcohol, Hepatitis, HIV screen
- •Abuse of alcohol
- •History of liver disease, or known hepatic or biliary abnormalities
- •The subject has recently received an investigational product
- •Donation of more than 500 mL blood within a 56 day period
- •Unwillingness or inability to follow the procedures outlined in the protocol
- •Use of prescription or non-prescription drugs
- •Subject is mentally or legally incapacitated
- •History of sensitivity to heparin or heparin-induced thrombocytopenia
- •Smoking or history or regular use of tobacco or nicotine-containing products
- •Unable to refrain from consumption of red wine, Seville oranges, grapefruit or grapefruit juice from 7 days prior to the first dose
- •History of cardiac disease
研究组 & 干预措施
GSK1322322 1000 mg IV
On Day 1 of Period 1, after an overnight fast, subjects will receive GSK1322322 1000 mg IV single dose (containing approximately 45.5 microcurie [μCi] radioactive 14C-GSK1322322) for intravenous infusion over 60 minutes.
干预措施: GSK1322322 1000 mg containing radioactive 14C-GSK1322322 (Drug)
GSK1322322 1200 mg Oral Solution
On Day 1 of Period 2, after an overnight fast, subjects will receive GSK1322322 1200 mg oral solution single dose (containing approximately 54.5 μCi radioactive 14C-GSK1322322).
干预措施: GSK1322322 1200 mg containing radioactive 14C-GSK1322322 (Drug)
结局指标
主要结局
Percent total recovery of radioactivity in urine and feces in each interval and cumulative
时间窗: Day 1 through Day 8 (and additional days, if required) of Period 1 and Period 2 (16 days or more)
Total recovery of radioactivity in urine and feces (as a percentage of total radioactive dose in each interval and cumulative)
Plasma pharmacokinetic (PK) parameters of GSK1322322 and radiolabeled compound following single IV or oral solution dose: AUC(0-infinity), AUC(0-t), Cmax, tmax, t1/2 for IV and oral solution regimens and CL and Vss for IV regimen only
时间窗: Day 1 through Day 8 of Period 1 and Period 2 (16 days)
Plasma PK parameters will be statistically summarized by treatment. Plasma concentration-time data will be analyzed by non-compartmental methods. Following PK parameters will be studied: Area under the concentration-time curve (AUC) from time zero (pre-dose) extrapolated to infinite time \[AUC(0-infinity)\], AUC(0-t), maximum observed concentration (Cmax), time of occurrence of Cmax (tmax), terminal phase half-life (t1/2) for IV and oral solution regimens and systemic clearance (CL) and volume of distribution (Vss) for IV regimen only.
次要结局
- Safety parameters including adverse events, clinical laboratory tests, concomitant medications, electrocardiograms, and vital signs(Duration of the study (56 days))