A Randomized, Open-Label, Parallel-Arm, Noninferiority Comparison of the Effects of Two Doses of LY2189265 and Insulin Glargine on Glycemic Control in Patients With Type 2 Diabetes on Stable Doses of Metformin and Glimepiride
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 810
- 试验地点
- 1
- 主要终点
- Change From Baseline to 52 Weeks Endpoint in Glycosylated Hemoglobin (HbA1c)
研究概览
简要总结
The purpose of this study is to determine if LY2189265 is effective in reducing hemoglobin A1c (HbA1c) and safe, as compared to Insulin Glargine in participants with Type 2 Diabetes. Participants must also be taking metformin and glimepiride.
详细描述
Rescue therapy refers to 1 of 2 types of additional therapy, each given for a different reason: any additional therapeutic intervention in participants who developed persistent, severe hyperglycemia despite full compliance with the assigned therapeutic regimen, or initiation of an alternative antihyperglycemic medication following study drug discontinuation. Participants who received rescue therapy were included in the analysis population, but only measurements obtained prior to the beginning of rescue therapy were included in specified efficacy analyses.
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
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Type 2 Diabetes not well controlled on 1, 2, or 3 oral antidiabetic medications (at least one of them must be metformin and/or a sulfonylurea)
- •Glycosylated hemoglobin (HbA1c) greater than or equal to 7 and less than or equal to 11 if taking 1 oral antidiabetic medication
- •HbA1c greater than or equal to 7 and less than or equal to 10 if on 2 or 3 oral antidiabetic medications
- •Accept treatment with metformin and glimepiride throughout the study, as per protocol
- •Willing to inject subcutaneous medication once weekly for LY2189265 or once daily for Insulin Glargine.
- •Stable weight for 3 months prior to screening
- •Body mass index (BMI) between 23 and 45 kilograms per square meter (kg/m^2)
- •Females of child bearing potential must test negative for pregnancy at screening by serum pregnancy test and be willing to use a reliable method of birth control during the study and for 1 month following the last dose of study drug
排除标准
- •Type 1 Diabetes
- •HbA1c equal to or less than 6.5 at randomization
- •Chronic insulin use
- •Taking drugs to promote weight loss by prescription or over the counter
- •Taking systemic steroids for greater than 14 days except for topical, eye, nasal, or inhaled
- •History of Heart Failure New York Heart Classification III or IV, or acute myocardial infarction, or stroke within 2 months of screening
- •Gastrointestinal (GI) problems such as diabetic gastroparesis or bariatric surgery (stomach stapling) or chronically taking drugs that directly affect GI motility
- •Hepatitis or liver disease or ALT (alanine transaminase) greater than 3.0 of upper normal limit
- •Acute or chronic pancreatitis of any form
- •Renal disease (kidney) with a serum creatinine of greater than or equal to 1.5 milligrams per deciliter (mg/dL) for males and greater than or equal to 1.4 mg/dL for females, or a creatinine clearance of less than 60 milliliters per minute (ml/min)
- •History (includes family) of type 2A or 2B Multiple Endocrine Neoplasia (MEN 2A or 2B) or medullary c-cell hyperplasia or thyroid cancer
- •A serum calcitonin greater than or equal to 20 picograms per milliliter (pcg/ml) at screening
- •Significant active autoimmune disease such as Lupus or Rheumatoid Arthritis
- •History of or active malignancy except skin or in situ cervical or prostate cancer for within last 5 years
- •Sickle cell, hemolytic anemia, or other hematological condition that may interfere with HbA1c testing
- •Organ transplant except cornea
- •Have enrolled in another clinical trial within the last 30 days
- •Have previously signed an informed consent or participated in a LY2189265 study
- •Have taken a glucagon-like peptide 1 (GLP-1) receptor agonist within the 3 months prior to screening
研究组 & 干预措施
LY2189265 1.5 mg
LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 78 weeks
Metformin: at least 1500 milligrams per day (mg/day), oral, for 78 weeks
Glimepiride: at least 4 mg/day, oral, for 78 weeks
干预措施: LY2189265 (Drug)
LY2189265 1.5 mg
LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 78 weeks
Metformin: at least 1500 milligrams per day (mg/day), oral, for 78 weeks
Glimepiride: at least 4 mg/day, oral, for 78 weeks
干预措施: Metformin (Drug)
LY2189265 1.5 mg
LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 78 weeks
Metformin: at least 1500 milligrams per day (mg/day), oral, for 78 weeks
Glimepiride: at least 4 mg/day, oral, for 78 weeks
干预措施: Glimepiride (Drug)
LY2189265 0.75 mg
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 78 weeks
Metformin: at least 1500 milligrams per day (mg/day), oral, for 78 weeks
Glimepiride: at least 4 mg/day, oral, for 78 weeks
干预措施: LY2189265 (Drug)
LY2189265 0.75 mg
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 78 weeks
Metformin: at least 1500 milligrams per day (mg/day), oral, for 78 weeks
Glimepiride: at least 4 mg/day, oral, for 78 weeks
干预措施: Metformin (Drug)
LY2189265 0.75 mg
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 78 weeks
Metformin: at least 1500 milligrams per day (mg/day), oral, for 78 weeks
Glimepiride: at least 4 mg/day, oral, for 78 weeks
干预措施: Glimepiride (Drug)
Insulin Glargine
Insulin Glargine: dose titration based on blood glucose measures, subcutaneous (SC), once daily for 78 weeks
Metformin: at least 1500 milligrams per day (mg/day), oral, for 78 weeks
Glimepiride: at least 4 mg/day, oral, for 78 weeks
干预措施: Insulin Glargine (Drug)
Insulin Glargine
Insulin Glargine: dose titration based on blood glucose measures, subcutaneous (SC), once daily for 78 weeks
Metformin: at least 1500 milligrams per day (mg/day), oral, for 78 weeks
Glimepiride: at least 4 mg/day, oral, for 78 weeks
干预措施: Metformin (Drug)
Insulin Glargine
Insulin Glargine: dose titration based on blood glucose measures, subcutaneous (SC), once daily for 78 weeks
Metformin: at least 1500 milligrams per day (mg/day), oral, for 78 weeks
Glimepiride: at least 4 mg/day, oral, for 78 weeks
干预措施: Glimepiride (Drug)
结局指标
主要结局
Change From Baseline to 52 Weeks Endpoint in Glycosylated Hemoglobin (HbA1c)
时间窗: Baseline, 52 weeks
Least Squares (LS) means were calculated using analysis of covariance (ANCOVA) with country and treatment as fixed effects and baseline HbA1c as a covariate.
次要结局
- Rate of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks(Baseline through 26, 52, and 78 weeks)
- Change From Baseline to 26, 52, and 78 Weeks on Blood Pressure(Baseline, 26, 52, and 78 weeks)
- Number of Participants Achieving Glycosylated Hemoglobin (HbA1c) Less Than or Equal to 6.5% at 26, 52 and 78 Weeks(26, 52, and 78 weeks)
- Number of Participants Achieving Glycosylated Hemoglobin (HbA1c) Less Than 7% at 26, 52 and 78 Weeks(26, 52, and 78 weeks)
- Change From Baseline to 52 and 78 Weeks in Updated Homeostasis Model Assessment of Beta-cell Function (HOMA2-%B) and Updated Homeostasis Model Assessment of Insulin Sensitivity (HOMA2-%S)(Baseline, 52, and 78 weeks)
- Change From Baseline to 26, 52 and 78 Weeks for Body Mass Index(Baseline, 26, 52, and 78 weeks)
- Change From Baseline to 26 Weeks and 78 Weeks Endpoint in Glycosylated Hemoglobin (HbA1c)(Baseline, 26 weeks, and 78 weeks)
- Change From Baseline to 52 and 78 Weeks in Glucagon Concentration(Baseline, 52, and 78 weeks)
- Change From Baseline to 26, 52 and 78 Weeks for Body Weight(Baseline, 26, 52, and 78 weeks)
- Change From Baseline to 26, 52 and 78 Weeks in the Impact of Weight on Self-Perception(Baseline, 26, 52, and 78 weeks)
- Number of Participants Requiring Additional Intervention Due to Hyperglycemia at 26, 52 and 78 Weeks(26, 52, and 78 weeks)
- Change From Baseline to 26, 52 and 78 Weeks for Daily Mean Blood Glucose Values From the 8-point Self-monitored Blood Glucose (SMBG) Profiles(Baseline, 26, 52, and 78 weeks)
- Change From Baseline to 26, 52 and 78 Weeks in the Low Blood Sugar Survey(Baseline, 26, 52, and 78 weeks)
- Number of Participants With Treatment Emergent Adverse Events at 26, 52 and 78 Weeks(26, 52, and 78 weeks)
- Number of Participants With LY2189265 Antibodies at 26, 52, 78 Weeks and 4 Weeks After Last Dose of Study Drug (83 Weeks Maximum)(Baseline, 26, 52, 78, and 83 weeks)
- Number of Self-reported Hypoglycemic Events at 26, 52 and 78 Weeks(Baseline through 26, 52, and 78 weeks)
- Change From Baseline to 26, 52 and 78 Weeks in the EuroQol 5 Dimension(Baseline, 26, 52, and 78 weeks)
- Change From Baseline to 26, 52 and 78 Weeks in the Impact of Weight on Activities of Daily Living(Baseline, 26, 52, and 78 weeks)
- Change From Baseline to 26, 52 and 78 Weeks on Pancreatic Enzymes(Baseline, 26, 52, and 78 weeks)
- Number of Participants With Adjudicated Pancreatitis at 26, 52 and 78 Weeks(Baseline through 26, 52, and 78 weeks)
- Change From Baseline to 26, 52 and 78 Weeks on Serum Calcitonin(Baseline, 26, 52, and 78 weeks)
- Change From Baseline to 26, 52 and 78 Weeks on Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval(Baseline, 26, 52, and 78 weeks)
- Number of Participants With Adjudicated Cardiovascular Events at 26, 52 and 78 Weeks(Baseline through 26, 52, and 78 weeks)
- Change in Baseline to 26, 52 and 78 Weeks on Pulse Rate(Baseline, 26, 52, and 78 weeks)
- Change From Baseline to 26, 52 and 78 Weeks on Electrocardiogram Parameters, Heart Rate(Baseline, 26, 52, and 78 weeks)