A Randomized, Placebo-Controlled Comparison of the Effects of Two Doses of LY2189265 or Exenatide on Glycemic Control in Patients With Type 2 Diabetes on Stable Doses of Metformin and Pioglitazone (AWARD-1: Assessment of Weekly Administration of LY2189265 in Diabetes-1)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 978
- 试验地点
- 1
- 主要终点
- Change From Baseline to 26 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 and safe in reducing hemoglobin A1c (HbA1c), as compared to placebo (no medicine), or exenatide in participants with Type 2 Diabetes. The participants must also be taking metformin and pioglitazone.
详细描述
During the study, if a participant developed persistent, severe hyperglycemia despite full compliance with the assigned therapeutic regimen, the participant received additional therapeutic intervention or initiation of an alternative antihyperglycemic medication following study drug discontinuation (rescue therapy). 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 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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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 (T2D) not well controlled on 1, 2, or 3 oral antidiabetic medications
- •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
- •Able to tolerate minimum dose of 1500 milligrams (mg) metformin a day and 30 mg pioglitazone per day.
- •Willing to inject subcutaneous (SC) medication up to 2 times per day
- •Stable weight for 3 months prior to screening
- •Body mass index (BMI) between 23 and 45 kilograms per meter squared (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 before randomization or 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 fluid retention or edema
- •History of Heart Failure New York Heart Classification II, III, or IV or acute myocardial infarction or stroke within 2 months of screening
- •Gastrointestinal (GI; stomach) problems such as diabetic gastroparesis or bariatric surgery (stomach stapling) or chronically taking drugs that directly affect GI motility
- •Hepatitis or liver disease or alanine transaminase (ALT) greater than 2.5 times the upper limit of normal
- •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 creatine 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 (pg/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 (dulaglutide) 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
1.5 mg LY2189265
LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks
Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks
Pioglitazone: at least 30 mg/day, oral, for 52 weeks
干预措施: LY2189265 (Drug)
1.5 mg LY2189265
LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks
Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks
Pioglitazone: at least 30 mg/day, oral, for 52 weeks
干预措施: Metformin (Drug)
1.5 mg LY2189265
LY2189265 (Dulaglutide): 1.5 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks
Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks
Pioglitazone: at least 30 mg/day, oral, for 52 weeks
干预措施: Pioglitazone (Drug)
0.75 mg LY2189265
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks
Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks
Pioglitazone: at least 30 mg/day, oral, for 52 weeks
干预措施: LY2189265 (Drug)
0.75 mg LY2189265
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks
Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks
Pioglitazone: at least 30 mg/day, oral, for 52 weeks
干预措施: Metformin (Drug)
0.75 mg LY2189265
LY2189265 (Dulaglutide): 0.75 milligrams (mg), subcutaneous (SC), once weekly for 52 weeks
Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks
Pioglitazone: at least 30 mg/day, oral, for 52 weeks
干预措施: Pioglitazone (Drug)
Exenatide
Exenatide: 5 micrograms (mcg), subcutaneous (SC), twice daily for 4 weeks, followed by 10 mcg, SC, twice daily for 48 weeks
Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks
Pioglitazone: at least 30 mg/day, oral, for 52 weeks
干预措施: Exenatide (Drug)
Exenatide
Exenatide: 5 micrograms (mcg), subcutaneous (SC), twice daily for 4 weeks, followed by 10 mcg, SC, twice daily for 48 weeks
Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks
Pioglitazone: at least 30 mg/day, oral, for 52 weeks
干预措施: Metformin (Drug)
Exenatide
Exenatide: 5 micrograms (mcg), subcutaneous (SC), twice daily for 4 weeks, followed by 10 mcg, SC, twice daily for 48 weeks
Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks
Pioglitazone: at least 30 mg/day, oral, for 52 weeks
干预措施: Pioglitazone (Drug)
Placebo
Placebo: subcutaneous (SC), once weekly for 26 weeks
LY2189265 (Dulaglutide): After 26 weeks, participants were randomized to receive either 0.75 milligrams (mg) or 1.5 mg, SC, once weekly for an additional 26 weeks (from week 26 through week 52).
Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks
Pioglitazone: at least 30 mg/day, oral, for 52 weeks
干预措施: LY2189265 (Drug)
Placebo
Placebo: subcutaneous (SC), once weekly for 26 weeks
LY2189265 (Dulaglutide): After 26 weeks, participants were randomized to receive either 0.75 milligrams (mg) or 1.5 mg, SC, once weekly for an additional 26 weeks (from week 26 through week 52).
Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks
Pioglitazone: at least 30 mg/day, oral, for 52 weeks
干预措施: Placebo (Drug)
Placebo
Placebo: subcutaneous (SC), once weekly for 26 weeks
LY2189265 (Dulaglutide): After 26 weeks, participants were randomized to receive either 0.75 milligrams (mg) or 1.5 mg, SC, once weekly for an additional 26 weeks (from week 26 through week 52).
Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks
Pioglitazone: at least 30 mg/day, oral, for 52 weeks
干预措施: Metformin (Drug)
Placebo
Placebo: subcutaneous (SC), once weekly for 26 weeks
LY2189265 (Dulaglutide): After 26 weeks, participants were randomized to receive either 0.75 milligrams (mg) or 1.5 mg, SC, once weekly for an additional 26 weeks (from week 26 through week 52).
Metformin: at least 1500 milligrams per day (mg/day), oral, for 52 weeks
Pioglitazone: at least 30 mg/day, oral, for 52 weeks
干预措施: Pioglitazone (Drug)
结局指标
主要结局
Change From Baseline to 26 Weeks Endpoint in Glycosylated Hemoglobin (HbA1c)
时间窗: Baseline, 26 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
- Change From Baseline to 26 Weeks for Body Weight(Baseline, 26 weeks)
- Change From Baseline to 26 Weeks for Daily Mean Blood Glucose Values From the 8-point Self-monitored Plasma Glucose (SMPG) Profiles(Baseline, 26 weeks)
- Change From Baseline to 52 Weeks in Updated Homeostasis Model Assessment of Beta-cell Function (HOMA2-%B) and Updated Homeostasis Model Assessment of Insulin Sensitivity (HOMA2-%S)(Baseline, 52 weeks)
- Change From Baseline to 26 Weeks on the Impact of Weight on Self-Perception(Baseline, 26 weeks)
- Change From Baseline to 52 Weeks for Body Weight(Baseline, 52 weeks)
- Percentage of Participants Attaining Glycosylated Hemoglobin (HbA1c) Less Than 7% and Less Than or Equal to 6.5% at 26 Weeks(Baseline, 26 weeks)
- Change From Baseline to 52 Weeks in the EuroQol 5(Baseline, 52 weeks)
- Change From Baseline to 52 Weeks in the Impact of Weight on Activities of Daily Living(Baseline, 52 weeks)
- Change From Baseline to 52 Weeks on Body Mass Index (BMI)(Baseline, 52 weeks)
- Change From Baseline to 52 Weeks for Daily Mean Blood Glucose Values From the 8-point Self-monitored Plasma Glucose (SMPG) Profiles(Baseline, 52 weeks)
- Change From Baseline to 26 Weeks in the Diabetes Treatment Satisfaction Questionnaire Status (DTSQs) Version(Baseline, 26 weeks)
- Change From Baseline to 26 Weeks on Blood Pressure(Baseline, 26 weeks)
- Number of Participants With LY2189265 Antibodies at 52 Weeks and 4 Weeks After Last Dose of Study Drug(26 weeks through 52 weeks and 53 weeks through 4 weeks after last dose)
- Number of Participants With Adjudicated Cardiovascular Events at 52 Weeks(Baseline through 52 weeks)
- Number of Participants With Adjudicated Pancreatitis at 26 Weeks(Baseline through 26 weeks)
- Change From Baseline to 52 Weeks on Serum Calcitonin(Baseline, 52 weeks)
- Change From Baseline to 52 Weeks Endpoint in Glycosylated Hemoglobin (HbA1c)(Baseline, 52 weeks)
- Change From Baseline to 26 Weeks on Body Mass Index (BMI)(Baseline, 26 weeks)
- Percentage of Participants Attaining Glycosylated Hemoglobin (HbA1c) Less Than 7% and Less Than or Equal to 6.5% at 52 Weeks(Baseline, 52 weeks)
- Change From Baseline to 26 Weeks in Updated Homeostasis Model Assessment of Beta-cell Function (HOMA2-%B) and Updated Homeostasis Model Assessment of Insulin Sensitivity (HOMA2-%S)(Baseline, 26 weeks)
- Change From Baseline to 52 Weeks in the Diabetes Treatment Satisfaction Questionnaire Status (DTSQs) and Change (DTSQc) Versions(Baseline, 52 weeks)
- Change From Baseline to 26 Weeks on Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval(Baseline, 26 weeks)
- Change From Baseline to 26 Weeks in the EuroQol 5(Baseline, 26 weeks)
- Change From Baseline to 26 Weeks in the Impact of Weight on Activities of Daily Living(Baseline, 26 weeks)
- Change From Baseline to 52 Weeks on Electrocardiogram Parameters, Fridericia Corrected QT (QTcF) Interval and PR Interval(Baseline, 52 weeks)
- Change From Baseline to 26 Weeks on Pancreatic Enzymes(Baseline, 26 weeks)
- Number of Participants With LY2189265 Antibodies at 26 Weeks(Baseline through 26 weeks)
- Change From Baseline to 52 Weeks on the Impact of Weight on Self-Perception(Baseline, 52 weeks)
- Number of Participants With Adjudicated Pancreatitis at 52 Weeks(Baseline through 52 weeks)
- Number of Self-reported Hypoglycemic Events at 52 Weeks(Baseline through 52 weeks)
- Change in Baseline to 26 Weeks on Pulse Rate(Baseline, 26 weeks)
- Change in Baseline to 52 Weeks on Pulse Rate(Baseline, 52 weeks)
- Change From Baseline to 52 Weeks on Blood Pressure(Baseline, 52 weeks)
- Change From Baseline to 52 Weeks on Pancreatic Enzymes(Baseline, 52 weeks)
- Change From Baseline to 26 Weeks on Serum Calcitonin(Baseline, 26 weeks)
- Number of Participants Requiring Rescue Therapy Due to Hyperglycemia at 52 Weeks(Baseline through 52 weeks)
- Number of Self-reported Hypoglycemic Events at 26 Weeks(Baseline through 26 weeks)
- Rate of Self-reported Hypoglycemic Events at 52 Weeks(Baseline through 52 weeks)
- Number of Participants With Treatment Emergent Adverse Events at 26 Weeks(Baseline through 26 weeks)
- Rate of Self-reported Hypoglycemic Events at 26 Weeks(Baseline through 26 weeks)
- Number of Participants Requiring Rescue Therapy Due to Hyperglycemia at 26 Weeks(Baseline through 26 weeks)
- Change From Baseline to 52 Weeks in Hematological and Biochemical Lab Values(Baseline, 52 weeks)
- Change From Baseline to 26 Weeks in N Terminal Pro Brain Natriuretic Peptide (NT-proBNP)(Baseline, 26 weeks)
- Number of Participants With Treatment Emergent Adverse Events at 52 Weeks(Baseline through 52 weeks)
- Change From Baseline to 26 Weeks in Hematological and Biochemical Lab Values(Baseline, 26 weeks)
- Pharmacokinetics: Area Under the Concentration Curve (AUC) for LY2189265(4 weeks, 13 weeks, 26 weeks, and 52 weeks)