A Single- and Multiple-Ascending Dose Study in Healthy Subjects to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of LY3298176 and Multiple Doses in Patients With Type 2 Diabetes Mellitus
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 142
- 试验地点
- 2
- 主要终点
- Number of Participants With One or More Serious Adverse Event(s) (SAEs)
研究概览
简要总结
The main purposes of this study are to determine:
- The safety of tirzepatide and any side effects that might be associated with it.
- How much tirzepatide gets into the bloodstream and how long it takes the body to get rid of it.
- How tirzepatide affects the levels of blood sugar.
This study includes 3 parts (A, B and C). Part A involves a single dose of tirzepatide taken as a subcutaneous (SC) injection just under the skin and will be approximately 10 weeks in duration, including screening. Parts B and C involve 4 doses of tirzepatide taken once weekly (over 4 weeks) as a SC injection just under the skin and is approximately 12-14 weeks in duration, including screening. Each participant will enroll in only one part.
This study is for research purposes only, and is not intended to treat any medical condition.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 21 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy participants (Parts A and B) and participants with T2DM diagnosed at least 1 year before enrollment (Part C)
- •Have a screening body mass index (BMI) of greater than 18.5 and less than or equal to 40.0 kilograms per meter squared (kg/m²), inclusive
- •Participants with T2DM (Part C only): have T2DM controlled with diet and exercise alone or are stable on a single oral antidiabetic medication (metformin for at least 30 days or sulfonylureas). Participants receiving sulfonylureas may participate only if this treatment is stopped for at least 6 weeks before dosing with study drug
排除标准
- •Have known allergies to tirzepatide, glucagon-like peptide (GLP)-1 analogs, or related compounds
- •Have an abnormality in the 12-lead electrocardiogram (ECG) at screening that, in the opinion of the investigator, increases the risks associated with participating in the study
- •Have a history or presence of pancreatitis (history of chronic pancreatitis or idiopathic acute pancreatitis), elevation in serum amylase or lipase (greater than 2-fold the upper limit of normal [ULN]) or gastrointestinal (GI) disorder (for example, relevant esophageal reflux or gall bladder disease) or any GI disease which impacts gastric emptying (for example, gastric bypass surgery, pyloric stenosis, with the exception of appendectomy) or could be aggravated by glucagon-like peptide-1 (GLP-1) analogs or dipeptidyl peptidase (DPP)-IV inhibitors
- •Participants with T2DM (Part C only)
- •Have had more than 1 episode of severe hypoglycemia, as defined by the American Diabetes Association criteria, within 6 months before entry into the study or has a history of hypoglycemia unawareness or poor recognition of hypoglycemic symptoms
- •All Study Participants (Parts B and C only)
- •have known allergies to tirzepatide, GLP-1 analogs, or related compounds, or acetaminophen
研究组 & 干预措施
Tirzepatide (Part A)
Participants received escalating single doses of either 0.25 milligram (mg) or 0.5mg or 1mg, or 2.5mg or 5mg or 8mg Tirzepatide by subcutaneous injection.
干预措施: Tirzepatide (Drug)
Placebo (Part A)
Participants received single dose of placebo by subcutaneous injection.
干预措施: Placebo (Drug)
Tirzepatide (Part B)
Participants received fixed doses of either 0.5mg or 1.5mg or 4.5mg Tirzepatide once weekly for four weeks or titrated doses of 5mg, 5mg, 8mg and 10mg Tirzepatide once weekly for four weeks by subcutaneous injection.
干预措施: Tirzepatide (Drug)
Placebo (Part B)
Participants received placebo once weekly for four weeks by subcutaneous injection.
干预措施: Placebo (Drug)
Dulaglutide (Part B)
Participants received 1.5mg Dulaglutide once weekly for four weeks by subcutaneous injection.
干预措施: Dulaglutide (Drug)
Tirzepatide (Part C)
Participants received fixed doses of either 0.5mg or 5mg Tirzepatide once weekly for four weeks or titrated doses of 5mg,5mg,10mg,10mg or 5mg,5mg,10mg,15mg Tirzepatide once weekly for four weeks by subcutaneous injection
干预措施: Tirzepatide (Drug)
Placebo (Part C)
Participants received placebo once weekly for four weeks by subcutaneous injection.
干预措施: Placebo (Drug)
结局指标
主要结局
Number of Participants With One or More Serious Adverse Event(s) (SAEs)
时间窗: Baseline through Day 43 (Part A) and Day 57 (Part B and C)
Number of participants with one or more SAEs considered by the investigator to be related to study drug administration. A summary of SAEs and other non-serious adverse events (AEs), regardless of causality, were reported in the Reported Adverse Events module
次要结局
- Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve (AUC) of Tirzepatide in Part A.(Predose, 8hours(h), 24h,48h,72h,96h,120h,168h,336h postdose, day 29, day 43)
- Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve (AUC) of Tirzepatide in Part B(Predose, 8hours(h), 24h,48h,72h,168h postdose)
- Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve (AUC) of Tirzepatide in Part C(Predose, 8hours(h), 24h,48h,72h,168h postdose)
- Pharmacodynamics (PD): Ratio of AUC of Glucose on Day 2 to Baseline (Part C)(Pre-glucose dose, 0.5, 1, 1.5, 2 hours post-glucose dose on Day -1 and Day 2)
- Pharmacodynamics (PD): Ratio of AUC of Glucose on Day 23 to Baseline (Part C)(Pre-glucose dose, 0.5, 1, 1.5, 2 hours post-glucose dose on Day -1 and Day 23)