A Single and Multiple Ascending Dose Study to Evaluate Safety, Tolerability, and Pharmacokinetics of the Oxyntomodulin Analog, LY2944876, in Healthy Japanese Subjects and Healthy Non-Japanese Subjects
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 48
- 试验地点
- 1
- 主要终点
- Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to Be Related to Study Drug Administration
研究概览
简要总结
LY2944876 is an investigative drug for the treatment of Type 2 Diabetes Mellitus. Part A of the study will assess the safety and tolerability of single doses of LY2944876 in Japanese participants. Participation is expected to last up to about 7 weeks, not including screening.
Part B of the study will investigate the safety and tolerability of multiple doses of LY2944876 in non Japanese participants. Participation is expected to last up to about 8 weeks, not including screening.
All doses will be administered as injections into the fatty layer just beneath the skin.
Screening is required within 28 days prior to the start of the study. All participants will attend a post study safety assessment approximately 6 weeks after their final dose.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Basic Science
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy males or female participants
- •Are first generation Japanese participants (Part A) or non-Japanese participants (Part B)
- •Have a body mass index (BMI) of 18.5 to 30 kilogram per meter square (kg/m^2), inclusive, for Part A and a BMI of 25 to 40 kg/m^2, inclusive, for Part B at screening
- •Have normal blood pressure and heart rate (after approximately 5 minutes supine and approximately 2 minutes standing) as determined by the investigator at screening
排除标准
- •Have known allergies to LY2944876, related compounds or any components of the formulation, or history of significant atopy
- •Have an abnormality in the 12-lead electrocardiogram (ECG) at screening and/or baseline that, in the opinion of the investigator, increases the risks associated with participating in the study
- •Have significant history of or current cardiovascular, respiratory, hepatic, renal, gastrointestinal (GI), endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; of constituting a risk when taking the study medication; or of interfering with the interpretation of data
- •Have a history of acute or chronic pancreatitis or elevation in serum lipase and/or amylase greater than 2 times the upper limit of normal (ULN) at screening and/or baseline
- •Have known or ongoing psychiatric disorders considered clinically significant in the opinion of the investigator
- •Have undergone any form of bariatric surgery
- •Have fasting blood glucose levels greater than or equal to (≥) 7 millimoles per liter (mmol/L) [≥126 milligrams per deciliter (mg/dL)] at screening
- •Have fasting triglycerides levels ≥300 mg/dL (3.4 mmol/L) at screening
- •Have obvious clinical signs or symptoms of liver disease, acute or chronic hepatitis, or an alanine transaminase (ALT) or aspartate aminotransferase (AST) levels greater than (>) 2.5 times the ULN at screening and/or baseline
- •Have used or intend to use medications that promote weight loss, within 3 months prior to screening, for the duration of the study
研究组 & 干预措施
Placebo (Single Dose, Cohorts 1-3)
Single dose of placebo matching LY2944876 administered subcutaneous (SC) on Day 1
干预措施: Placebo (Drug)
LY2944876 (Single Dose, Cohorts 1-3)
Single dose of 10 milligrams (mg) of LY2944876 administered SC on Day 1
干预措施: LY2944876 (Drug)
Placebo (Multiple Dose, Cohort 4)
Placebo matching LY2944876 administered once daily SC on Days 1-7
干预措施: Placebo (Drug)
LY2944876 (Multiple Dose, Cohort 4)
40 mg LY2944876 administered once daily SC on Days 1-7
干预措施: LY2944876 (Drug)
Placebo (Multiple, Cohort 5)
Placebo matching LY2944876 administered once daily SC on Days 1, 4, 6, 8, 10 and 12
干预措施: Placebo (Drug)
LY2944876 (Multiple Dose, Cohort 5, Titrated)
LY2944876 in titrated doses of 15 mg on Day 1, 30 mg on Day 4, up to 60 mg on Day 6, and up to 80 mg on Days 8, 10 and 12 administered once daily SC
干预措施: LY2944876 (Drug)
结局指标
主要结局
Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to Be Related to Study Drug Administration
时间窗: Pre-dose (PRD) through Study Completion (Up to Day 40)
An SAE is any adverse event that results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. The number of participants with 1 or more SAEs considered by the investigator to be related to study drug administration is reported. 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: Area Under the Concentration Versus Time Curve - Time Zero to 168 Hours Post-dose [AUC(0-168h)] of LY2944876(Cohorts1-3:Day1 PRD,8,12,24,32,48,56,72,96,168Hrs;Days15,28,42:Cohort4:Day1 PRD,12 Hrs;Days2,3,4,5,6 PRD;Day7 PRD,12,24,36,48,56,72,96,168 Hrs;Days21,34,49: Cohort 5:Day1 PRD,12,24,48 Hrs;Days4,6,8,10 PRD;Day12 PRD,12,24,36,48,56,72,96,168 Hrs;Day26,39,53)
- Pharmacokinetics: Maximum Concentration (Cmax) of LY2944876(Cohorts1-3:Day1 PRD,8,12,24,32,48,56,72,96,168Hrs;Days15,28,42:Cohort4:Day1 PRD,12 Hrs;Days2,3,4,5,6 PRD;Day7 PRD,12,24,36,48,56,72,96,168 Hrs;Days21,34,49: Cohort 5:Day1 PRD,12,24,48 Hrs;Days4,6,8,10 PRD;Day12 PRD,12,24,36,48,56,72,96,168 Hrs;Day26,39,53)