A 2-Part Trial: a Randomized 6-day Repeat-dose, Parallel-group Study in Subjects With T2DM to Assess the Safety and Tolerability of GSK1614235 Compared to Placebo and Sitagliptin; and a Randomized Single-dose, Food Effect Study in Healthy Volunteers to Assess Safety and Tolerability of GSK1614235
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 72
- 试验地点
- 1
- 主要终点
- Part A: Safety, tolerability parameters: adverse events, gastro-intestinal side effects, subject reported outcomes, clinical laboratory results, ECGs and vital signs
研究概览
简要总结
The purpose of Part A of this study is to test whether repeated doses of the study drug (GSK1614235) are safe and well tolerated (i.e. do not produce unacceptable side effects) and whether we can obtain some preliminary information as to whether it works in lowering blood glucose levels. We will do this by comparing the effect of the study drug with placebo (no drug present) and against a drug (sitagliptin) known to control blood glucose in the treatment of diabetes.
The purpose of Part B of this study is to determine the how the timing of dosing, relative to meals, affects the response to study drug.
详细描述
Part A is a double-blind, randomized, parallel group, dose-ranging study, in subjects with type 2 diabetes mellitus to assess safety, tolerability, and to estimate the pharmacodynamic effects when subjects receive repeated doses of placebo, sitagliptin (Januvia), or GSK1614235. The target is to explore the best doses of GSK1614235 that provide glucose control with minimal adverse effects.
There will be at least 4 cohorts of subjects:
- Cohort 1: 8 subjects randomized to receive placebo, 100mg sitagliptin QD, or 1mg GSK1612435 BID
- Cohort 2: 6 subjects randomized to receive placebo, 100mg sitagliptin QD, or 5mg GSK1612435 BID.
- Cohort 3: 6 subjects randomized to receive placebo, 100mg sitagliptin QD, or 20mg GSK1612435 BID.
- Cohort 4: 20-40 subjects randomized to receive placebo, 100mg sitagliptin QD, or GSK1612435 BID, (potential doses of 0.25 to 40mg BID), depending on safety, tolerability, and glucose results of Cohorts 1, 2, and 3.
- Cohort 5: 12 subjects randomized to receive placebo or GSK1614235 BID (potential doses of up to 80mg BID), depending on safety, tolerability, and glucose results of Cohorts 1, 2, 3, and 4.
- Cohort 6: 24 subjects randomized to receive GSK1614235 BID (20BID), or sitagliptin (100mg QD).
After subjects have successfully completed the screening procedures, they will be asked to discontinue prior anti-diabetic therapy at least 72 h before admission to the research facility and remain off of the medications until the completion of the follow-up visit (total of ~14 days). Subjects will be admitted to the research facility on the evening of Day -2 in preparation to begin baseline assessments, including PD, on Day -1 (for their particular cohort). Beginning on Day 1, subjects will receive a single dose of GSK1614235 and undergo PK sampling, and on Day 2 through Day 6, subjects will be dosed on a twice daily dosing schedule with doses administered immediately before breakfast and the evening meal. Day 6 includes intensive assessments of PK and PD parameters in addition to routine safety monitoring.
Part B is a double-blind, randomized, single-dose, 3-way crossover study in 12 subjects. A well-tolerated dose of GSK1614235 that provides a meaningful pharmacodynamic response based on data from Part A will be administered in both fed and fasted states. It is not anticipated that the dose for Part B will exceed single doses of 40mg.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 30 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
GSK1614235
Glucose lowering agent under investigation.
干预措施: GSK1614235 (Drug)
Sitagliptin
Glucose lowering comparator
干预措施: Sitagliptin (Drug)
Placebo
Placebo to match GSK1614235 and placebo to match Sitagliptin
干预措施: Placebo (Other)
结局指标
主要结局
Part A: Safety, tolerability parameters: adverse events, gastro-intestinal side effects, subject reported outcomes, clinical laboratory results, ECGs and vital signs
时间窗: 6 days
Part B: Safety, tolerability parameters: adverse events, gastro-intestinal side effects, subject reported outcomes, clinical laboratory results, ECGs and vital signs
时间窗: 1 day
次要结局
- Part A: Pharmacodynamics(6 days)
- Part A: Pharmacokinetics(6 days)
- Part B: Pharmacokinetics(1 day)
- Part B: Pharmacodynamics(1 day)
- Part B: 3-O-Methyl-Glucose Kinetics(1 day)