Randomized, Double-Blind, Placebo-Controlled, Multiple Ascending Oral Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of LGD-6972 in Healthy Subjects and in Subjects With Type 2 Diabetes Mellitus
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 48
- 试验地点
- 3
- 主要终点
- Number of participants with one or more drug related adverse events or serious adverse events
研究概览
简要总结
Ligand Pharmaceuticals Incorporated is developing LGD-6972, a novel, orally-bioavailable addition to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. The mechanism of action of LGD-6972 is to reduce the excess liver glucose production characteristic of type 2 diabetes mellitus that is a major contributor to hyperglycemia. This clinical trial will evaluate the safety and tolerability of escalating doses LGD-6972 administered daily over 2 weeks in both healthy subjects and subjects with type 2 diabetes mellitus.
详细描述
This is to be a randomized, double-blind, placebo-controlled, sequential, multiple oral dose study conducted in normoglycemic healthy subjects (NHS) (Part 1) and subjects with type 2 diabetes mellitus (T2DM) who are treated with monotherapy metformin (a stable dose at randomization) along with diet and exercise (Part 2). Subjects with T2DM who are not on a stable dose of metformin but meet all other entry criteria may be enrolled in the study at the discretion of the Investigator, but must undergo a stabilization period of at least 12 weeks before determining eligibility for the study. In Part 1, a single group of healthy subjects will be dosed with repeated oral doses of 15 mg of LGD-6972 or placebo once daily (QD) for 14 days. In Part 2, a maximum of 3 groups of subjects with T2DM will be dosed with 3 sequential, increasing doses of LGD-6972 (5 mg, 10 mg or 15 mg) or placebo QD for 14 days.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 21 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
Part 1: LGD-6972 15 mg
15 mg LGD-6972 administered once daily (QD) for 14 days.
干预措施: LGD-6972 (Drug)
Part 1: Placebo (Captisol ®)
Placebo administered once daily (QD) for 14 days.
干预措施: Placebo (Captisol ®) (Drug)
Part 2: LGD-6972 5 mg
5 mg LGD-6972 administered orally QD for 14 days.
干预措施: LGD-6972 (Drug)
Part 2: LGD-6972 10 mg
10 mg LGD-6972 administered orally QD for 14 days.
干预措施: LGD-6972 (Drug)
Part 2: LGD-6972 15 mg
15 mg LGD-6972 administered orally QD for 14 days.
干预措施: LGD-6972 (Drug)
Part 2: Placebo (Captisol ®)
Placebo administered orally QD for 14 days.
干预措施: Placebo (Captisol ®) (Drug)
结局指标
主要结局
Number of participants with one or more drug related adverse events or serious adverse events
时间窗: At least 14 days after last dose
Safety and tolerability of repeat (14 days for normoglycemic healthy subjects (NHS) and 14 days for type 2 diabetes mellitus (T2DM) subjects) and sequential increasing oral doses of LGD-6972 in NHS and subjects withT2DM will be compared to NHS and T2DM subjects receiving placebo.
次要结局
- Pharmacokinetic (PK) profile (area under the concentration curve (AUC) of LGD-6972 after repeat oral doses in NHS and in subjects with T2DM(14 days)
- Change from baseline in fasting plasma glucose measured 24 hours after first dose and pre-dose Day 14 of treatment with LGD-6972 in NHS(14 days)
- Change from baseline in fasting plasma glucagon measured 24 hours after first dose and pre-dose Day 14 of treatment with LGD-6972 in NHS(14 days)
- Change from baseline in active and total glucagon-like-peptide (GLP-1) in fasting plasma measured 24 hours after first dose and pre-dose Day 14 of treatment with LGD-6972 in NHS(14 days)
- Change from baseline in fasting plasma glucose measured 24 hours after first dose and at Day 14 of treatment with LGD-6972 in subjects with T2DM(14 days)
- Change from baseline in fasting plasma glucagon measured 24 hours after first dose and at Day 14 of treatment with LGD-6972 in subjects with T2DM(14 days)
- Change from baseline in fasting plasma insulin measured 24 hours after first dose and at Day 14 of treatment with LGD-6972 in subjects with T2DM(14 days)
- Change from baseline in fasting plasma active and total GLP-1 measured 24 hours after first dose and at Day 14 of treatment with LGD-6972 in subjects with T2DM(14 days)
- Change from baseline in 7-point weighted mean glucose during 14 days of treatment with different doses of LGD-6972 in subjects with T2DM(14 days)
- Hemoglobin A1c response during 14 days of treatment with different dosages of LGD-6972 in subjects with T2DM(14 days)
- PK profile (maximum concentration (Cmax) of LGD-6972 after repeat oral doses in NHS and in subjects with T2DM(14 days)