Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Multiple-Ascending Subcutaneous Doses of LY3493269 in Patients With Type 2 Diabetes Mellitus
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 56
- 试验地点
- 3
- 主要终点
- Number of Participants With One or More Treatment-Emergent Adverse Event(s) (TEAEs) and Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration
研究概览
简要总结
The main purpose of this study is to determine the side effects related to LY3493269 in participants with type 2 diabetes. Blood tests will be performed to check concentrations of LY3493269 in the bloodstream. Each enrolled participant will receive LY3493269, dulaglutide, or placebo. The study will last up to approximately 16 weeks for each participant and may include up to 11 visits.
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
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Are male or female not of childbearing potential
- •Have a body mass index of 23 to 50 kilograms per square meter (kg/m²), inclusive, at screening
- •Have had a stable body weight (<5% body weight change) for the 3 months prior to screening
- •Have not modified their diet or adopted any nutritional lifestyle modification in the 3 months prior to screening
- •Have type 2 diabetes mellitus (T2DM) controlled with diet and exercise alone or are on a stable dose of metformin for at least 3 months before screening. Patients with comorbid conditions commonly associated with diabetes (for example, hypertension, hypercholesterolemia, hypothyroidism) may be eligible for inclusion if conditions are assessed by the investigator to be well controlled and stable for at least 3 months prior to screening
- •Have an HbA1c of at least 7.0% and no more than 10.5% at screening
- •Have clinical laboratory test results within the normal range for the population or investigative site, or with abnormalities deemed not clinically significant by the investigator
排除标准
- •Have type 1 diabetes mellitus or latent autoimmune diabetes in adults
- •Have uncontrolled diabetes, defined as an episode of ketoacidosis or hyperosmolar state requiring hospitalization in the 6 months prior to screening
- •Have a history of proliferative diabetic retinopathy, diabetic maculopathy, or severe nonproliferative diabetic retinopathy that requires acute treatment
- •Have had more than 1 episode of severe hypoglycemia, as defined by the American Diabetes Association criteria, within 6 months before screening or has a history of hypoglycemia unawareness or poor recognition of hypoglycemic symptoms.
- •Have a definitive diagnosis of autonomic neuropathy as evidenced by urinary retention, resting tachycardia, orthostatic hypotension, or diabetic diarrhea
- •Have a history of acute or chronic pancreatitis
- •Have a self or family history (first-degree relative) of multiple endocrine neoplasia type 2A or type 2B, thyroid C-cell hyperplasia, or medullary thyroid carcinoma
- •Have calcitonin levels of 20 picograms per millilitre (pg/mL) or more at screening
研究组 & 干预措施
1.5 milligrams (mg) Dulaglutide
Participants received 1.5 mg dulaglutide subcutaneously (SC) once weekly (QW) for 4 weeks.
干预措施: Dulaglutide (Drug)
0.3 mg LY3493269
Participants received 4 fixed dosed of 0.3 mg LY3493269 SC QW for 4 weeks.
干预措施: LY3493269 (Drug)
1 mg LY3493269
Participants received 4 fixed dosed of 1 mg LY3493269 SC QW for 4 weeks.
干预措施: LY3493269 (Drug)
0.75/1.5/3 mg LY3493269
Participants received LY3493269 0.75 mg on week 1, 1.5 mg on week 2 and 3 mg on week 3 and 4 SC as weekly doses.
干预措施: LY3493269 (Drug)
1.5/3/4/5 mg LY3493269
Participants received LY3493269 1.5 mg on week 1, 3 mg on week 2, 4 mg on week 3 and 5 mg on week 4 as weekly doses.
干预措施: LY3493269 (Drug)
Placebo
Participants received placebo subcutaneously (SC) once weekly (QW) for 4 weeks.
干预措施: Placebo (Drug)
结局指标
主要结局
Number of Participants With One or More Treatment-Emergent Adverse Event(s) (TEAEs) and Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration
时间窗: Baseline through final follow-up at Day 57
TEAE is an untoward medical occurrence that emerges during a defined treatment period, having been absent pretreatment, or worsens relative to the pretreatment state, and does not necessarily have to have a causal relationship with this treatment. An SAE is defined as any untoward medical occurrence that, at any dose: 1. Results in death 2. Is life-threatening 3. Requires inpatient hospitalization or prolongation of existing hospitalization 4. Results in persistent disability/incapacity 5. Is a congenital anomaly/birth defect 6. Other situations: Based on medical or scientific judgement. A summary of SAEs, TEAEs and other non-serious adverse events (AEs), regardless of causality, will be reported in the Reported Adverse Events module
次要结局
- Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to 168 Hours Postdose AUC(0-168) of LY3493269(Predose, 6, 12, 24, 48, 72, 96 and 168 h postdose at Weeks 1 and 4.)
- PK: Maximum Observed Drug Concentration (Cmax) of LY3493269(Predose, 6, 12, 24, 48, 72, 96 and 168 h postdose at Weeks 1 and 4.)
- Pharmacodynamics (PD):Change From Baseline to Day 29 in Fasting Plasma Glucose(Baseline, Day 29)