A First Time in Human, Single Blind, Randomized, Placebo-controlled,Dose Escalating Crossover Study to Evaluate the Safety,Tolerability, Pharmacokinetic and Pharmacodynamic Parameters of Single Doses of GSK2330672 in Healthy Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 17
- 试验地点
- 1
- 主要终点
- Change in vital signs
研究概览
简要总结
The purpose of this study is to look at the safety and tolerability of increasing single doses of GSK2330672 in healthy volunteers.
详细描述
This is a single blind, randomized, placebo-controlled, dose escalating, crossover, first time in human study to examine safety, tolerability, pharmacokinetic and pharmacodynamic parameters of GSK233672. Single blind indicates that the subjects and investigator are blinded to treatment but the GSK study team could be unblinded for ongoing review of interim safety data required for dose escalation.
Subjects will participate in 4 dosing periods. Subjects will enter the clinic prior to dinner time on the evening of Day -1 of each period and will remain in residence through the morning of Day 3. Barring any safety or tolerability concerns, subjects will be released at this time provided they have had at least 1 bowel movement after dosing in the clinic.
Subjects will return for their next scheduled dosing period. This process will be repeated for each dosing period. Subjects will return approximately 1 week after check out from their last dosing period for a follow up visit. Subjects will receive standardized meals meeting specific criteria starting with dinner on Day-1 and continuing through Day 1. Standard meals will be provided for the remainder of their stay in the clinic. After an overnight fast, subjects will take their study drug on the morning of Day 1. Dosing will be followed by breakfast and frequent blood sampling to assess pharmacokinetic and pharmacodynamic parameters. Scheduled assessments of heart rate, blood pressure, respiratory rate, ECGs, and clinical laboratories will be obtained to monitor subject safety. Subjects will be connected to cardiac telemetry monitors and will periodically undergo spirometry testing of ventilation parameters. Stool form and frequency of bowel movements will be recorded. All fecal samples will be collected from participants for 48 hours after dosing of study drug, or until they have had at least 1 bowel movement after dosing, whichever occurs first.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 60 Years(Adult)
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •healthy volunteer
- •18-60 yrs of age
- •for subjects age 50 and above: negative fecal occult blood test within 3 months prior to expected start of dosing, and normal results from sigmoidoscopy or colonoscopy within 5 yrs prior to dosing.
- •if female, must be of non-childbearing potential
排除标准
- •pregnant or breastfeeding females
- •positive HIV
- •positive Hep B, or Hep C within 3 months of screening
- •positive drugs of abuse screening
- •triglycerides > 250 mg/dL
- •current or chronic history of liver disease
- •any gastrointestinal or gastrointestinal related conditions that could affect fat or bile acid reabsorption
- •pancreatitis
- •colon cancer or 1st degree relative who has had colon cancer
- •abnormal lung function tests
- •inability to perform lung function tests
- •unwilling to abstain from smoking, alcohol, caffeine, illicit drugs as directed by the site staff
- •exposure to more than 4 new chemical entities in the 12 months prior to the first dosing day.
- •where participation in the study would results in donation of more than approximately 550mL of blood in a 56-day period.
研究组 & 干预措施
GSK2330672
experimental study drug
干预措施: 0.1 mg GSK2330672 (Drug)
GSK2330672
experimental study drug
干预措施: 0.3 mg GSK2330672 (Drug)
GSK2330672
experimental study drug
干预措施: 1 mg GSK2330672 (Drug)
GSK2330672
experimental study drug
干预措施: 3 mg GSK2330672 (Drug)
GSK2330672
experimental study drug
干预措施: 10 mg GSK2330672 (Drug)
GSK2330672
experimental study drug
干预措施: 30 mg GSK2330672 (Drug)
GSK2330672
experimental study drug
干预措施: 60 mg GSK2330672 (Drug)
Placebo
placebo
干预措施: placebo (Drug)
结局指标
主要结局
Change in vital signs
时间窗: 1, 2, 4, 8, 12, 24, 48 hours
frequency and absolute value change in heart rate, blood pressure, respiration rate relative to placebo
Adverse events relative to placebo
时间窗: 48 hour monitoring
Frequency and severity of adverse events relative to placebo
Changes in clinical lab results
时间窗: 24 hours
Changes in clinical chemistry, hematology, urinalysis results relative to placebo
ECGs relative to placebo
时间窗: 1, 2, 4, 8, 12, 24, 48 hours
frequency of clinically significant changes in 12-lead ECG parameters relative to placebo
lung function tests
时间窗: 1, 3, 8, 24 hours
Measure changes in FEV, FVC, FEF 25-75%, PEFR relative to placebo
次要结局
- Measurement of half life (t 1/2) of study drug(0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3.5, 5, 6.5, 8, 9.5, 12.5 hours)
- Measurement of apparent clearance (CL/F) of the study drug(0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3.5, 5, 6.5, 8, 9.5, 12.5 hours)
- Measurement of the apparent volume of distribution (V/F) of the study drug(0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3.5, 5, 6.5, 8, 9.5, 12.5 hours)
- Measurement of the maximum concentration (Cmax) for study drug(0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3.5, 5, 6.5, 8, 9.5, 12.5 hours)
- Measurement of the time to achieve maximum concentration (tmax) for study drug(0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3.5, 5, 6.5, 8, 9.5, 12.5 hours)
- Measurement of area under the curve (AUC) for study drug(0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3.5, 5, 6.5, 8, 9.5, 12.5 hours)
