A Phase 1b/2a, Randomized, Double-blind, Placebo-controlled, Study of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Multiple Ascending Doses of GSBR-1290 in Adult Overweight or Obese Healthy Subjects and in Subjects With Type 2 Diabetes Mellitus on Metformin
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 142
- 试验地点
- 4
- 主要终点
- Incidence, severity and relationship of AE/SAE, vital signs, laboratory measures and ECG to assess safety and tolerability of multiple oral doses of GSBR-1290 in HOV and T2DM
研究概览
简要总结
This study will evaluate safety, tolerability, pharmacokinetic (PK) profile, and pharmacodynamic (PD) effects on GSBR-1290 in healthy overweight/obese volunteers (HOV) and Type 2 Diabetes Mellitus on Metformin (T2DM) This study includes 5 planned cohorts. Participants will receive multiple-ascending doses of GSBR-1290 or Placebo from Day 1 to Day 84
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
- Triple (Participant, Care Provider, Investigator)
盲法说明
This is a double-blind study in which the GSBR-1290 and the matching placebo are matching in appearance
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- •History or presence of significant cardiovascular, pulmonary, hepatic, renal, hematological, gastrointestinal, endocrine, immunologic, dermatologic or neurological disease, including any acute illness or major surgery within the major 3 months
- •A sitting BP after resting for 5 minutes > 160mm Hg systolic or > 100 mm Hg diastolic or an apical pulse rate <50 or >100 beats per minute.
- •Evidence of abnormality on the screening visit ECG, or a history of known arrhythmia or prolonged QTcF pr prolonged QRS interval
- •Liver function test results elevated > 2.0-fold above the ULN for gamma glutamyl transferase, alkaline phosphatase, aspartate aminotransferase or alanine aminotransferase. Bilirubin above the ULN
- •Estimated glomerular filtration rate < 60mL/min/1.73 m2 body surface area
- •Known hypersensitivity to any of the study drug ingredients
- •Any other condition or prior therapy that would make the participant unsuitable for this study
研究组 & 干预措施
Cohort 1
Patients will receive once daily doses of study drug (GSBR-1290 or Placebo) for a total of 4 weeks
干预措施: GSBR-1290 (Drug)
Cohort 1
Patients will receive once daily doses of study drug (GSBR-1290 or Placebo) for a total of 4 weeks
干预措施: Placebo (Drug)
Cohort 2
Patients will receive once daily doses of study drug (GSBR-1290 or Placebo) for a total of 4 weeks
干预措施: GSBR-1290 (Drug)
Cohort 2
Patients will receive once daily doses of study drug (GSBR-1290 or Placebo) for a total of 4 weeks
干预措施: Placebo (Drug)
Cohort 3
Patients will receive once daily doses of study drug (GSBR-1290 or Placebo) for a total of 4 weeks
干预措施: GSBR-1290 (Drug)
Cohort 3
Patients will receive once daily doses of study drug (GSBR-1290 or Placebo) for a total of 4 weeks
干预措施: Placebo (Drug)
Cohort 4
HOV participants (Cohort 4) will receive multiple-ascending doses of GSBR-1290 or placebo for a total of 12 weeks
干预措施: GSBR-1290 (Drug)
Cohort 4
HOV participants (Cohort 4) will receive multiple-ascending doses of GSBR-1290 or placebo for a total of 12 weeks
干预措施: Placebo (Drug)
Cohort 5
Participants with T2DM(Cohort 5) will be randomized to placebo, low-dose, or high-dose arms. Participants in the low-dose, high-dose or placebo arms will receive multiple-ascending doses for 12 weeks
干预措施: GSBR-1290 (Drug)
Cohort 5
Participants with T2DM(Cohort 5) will be randomized to placebo, low-dose, or high-dose arms. Participants in the low-dose, high-dose or placebo arms will receive multiple-ascending doses for 12 weeks
干预措施: Placebo (Drug)
结局指标
主要结局
Incidence, severity and relationship of AE/SAE, vital signs, laboratory measures and ECG to assess safety and tolerability of multiple oral doses of GSBR-1290 in HOV and T2DM
时间窗: 42 days
次要结局
- Identification of GSBR-1290 metabolites following oral administration of multiple doses in plasma(31 days)
- Analysis of Cmax at specified timepoints predose and postdose to calculate PK parameters(31 days)
- Analysis of Tmax at specified timepoints predose and postdose to calculate PK parameters(31 days)
- Analysis of AUC at specified timepoints predose and postdose to calculate PK parameters(31 days)