NCT00853151已完成1 期
A Proof of Concept Study to Evaluate the Coadministration of TT223 Given Daily and LY2428757 Given Once-Weekly for Four Weeks in Patients With Type 2 Diabetes Mellitus
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 131
- 试验地点
- 1
- 主要终点
- Change From Baseline in Glycosylated Hemoglobin (HbA1c) at 6-Month Endpoint
研究概览
简要总结
Test the safety, tolerability and improvement of blood sugar control with combination therapy in individuals with Type 2 Diabetes.
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
- Triple (Participant, Care Provider, 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
- •Written informed consent
- •Have type 2 diabetes mellitus (T2DM) for at least 6 months
- •Currently treated with diet and exercise alone or in combination with stable metformin
- •Glycosylated hemoglobin (HbA1c) 7.0% to 10.0%
- •Ages 18 to 70 years
- •Women not of childbearing potential
- •Body mass index (BMI) between 25 and 40 kilograms per meters squared (kg/m^2), and stable weight in the 3 months prior to screening.
排除标准
- •Use of diabetes medicine other than metformin in past 3 months
- •Gastrointestinal disease or surgery or drugs that significantly impacts gastric filling, emptying or motility; ongoing cholelithiasis or cholecystitis.
- •Chronic, daily proton pump inhibitors (PPIs) and histamine (H2) antagonists.
- •Severe hypoglycemia or hyperglycemia
- •Advanced microvascular diabetes complications
- •Medications to promote weight loss.
- •Breastfeeding women
- •Cardiac autonomic neuropathy
- •In the past 6 months have cardiac disease with functional status that is Class II-IV or a history of myocardial infarction, unstable angina, coronary artery bypass graft, percutaneous coronary intervention, transient ischemic attack, cerebrovascular accident (stroke), or decompensated congestive heart failure.
- •History of a supraventricular or ventricular tachycardia, pacemaker implantation, or other cardiac arrhythmia: Poorly controlled hypertension, malignant hypertension, renal artery stenosis, and/or evidence of labile blood pressure including symptomatic postural hypotension.
- •Electrocardiograms (ECG) abnormality or medication that impairs the ability to measure QT interval (QT), or correct the QT interval (QT) for rate.
- •QT interval Bazett corrected (QTcB) >450 milliseconds (msec) or PR interval (PR) >220 milliseconds (msec)
- •Personal or family history of long QT interval (QT) syndrome, sudden death, or unexplained syncope
- •Clinical signs or symptoms of liver disease, acute or chronic hepatitis, or alanine transaminase levels > 2.5 times the upper limit of the reference range
- •Hypertriglyceridemia > 400 mg/deciliter (dL)
- •Inadequately treated hypothyroidism or hyperthyroidism
- •Peptic ulcer disease and/or gastrointestinal bleeding/perforation.
- •Known pentagastrin hypersensitivity
- •Impaired renal function
- •Transplanted organ.
- •Active, uncontrolled endocrine or autoimmune abnormality
- •> 2 weeks systemic glucocorticoid therapy
- •Ongoing courses of non-steroidal anti-inflammatory drugs (NSAIDs), except for aspirin 81-325 milligrams (mg)
- •Diagnosed malignancy or in remission for less than 5 years.
- •Prior acute or chronic pancreatitis or elevated serum lipase or amylase
- •Current central nervous system stimulant
- •Other conditions that preclude the participant from participating, following or completing the protocol.
- •Chronic infection
- •Personnel affiliated with the study and their immediate families.
- •Within 30 days of the initial dose of study drug, have participated in an interventional medical, surgical, or pharmaceutical study in which a medical or surgical treatment was given.
- •Have previously completed or withdrawn from this study after providing informed consent.
- •Are currently enrolled in, or discontinued within the last 30 days from, a clinical trial involving an off-label use of an investigational drug or device (other than the study drug/device used in this study), or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study.
研究组 & 干预措施
LY2428757 plus TT223 3 milligrams (mg)
Experimental
Weekly LY2428757 plus 3 milligrams (mg) daily TT223
干预措施: LY2428757 (Drug)
LY2428757 plus TT223 3 milligrams (mg)
Experimental
Weekly LY2428757 plus 3 milligrams (mg) daily TT223
干预措施: TT223 (Drug)
LY2428757 plus TT223 2mg
Experimental
Weekly LY2428757 plus 2 mg daily TT223
干预措施: LY2428757 (Drug)
LY2428757 plus TT223 2mg
Experimental
Weekly LY2428757 plus 2 mg daily TT223
干预措施: TT223 (Drug)
LY2428757 plus placebo
Experimental
Weekly LY2428757 plus daily TT223 placebo
干预措施: LY2428757 (Drug)
LY2428757 plus placebo
Experimental
Weekly LY2428757 plus daily TT223 placebo
干预措施: Placebo for TT223 (Drug)
Placebo plus Placebo
Placebo Comparator
Weekly LY2428757 placebo plus daily TT223 placebo
干预措施: Placebo for LY2428757 (Drug)
Placebo plus Placebo
Placebo Comparator
Weekly LY2428757 placebo plus daily TT223 placebo
干预措施: Placebo for TT223 (Drug)
结局指标
主要结局
Change From Baseline in Glycosylated Hemoglobin (HbA1c) at 6-Month Endpoint
时间窗: Baseline (Week -1), 6 months
Values obtained from repeated measures analysis, which included the fixed categorical effects of treatment, baseline therapy strata (metformin versus diet and exercise \[D\&E\]), visit, and treatment-by-visit interaction, as well as the continuous, fixed covariate of baseline glycosylated hemoglobin (HbA1c). Change from baseline means the absolute change from baseline (endpoint-baseline).
次要结局
- Change From Baseline in Glycosylated Hemoglobin (HbA1c) at 4-Week Endpoint(Baseline (Week -1), 4 weeks)
- Change From Baseline in Mixed-Meal Tolerance Test (MMTT) Response - Glucose Area Under the Curve (AUC) at 3-Week and 6-Month Endpoints(Baseline (Week -1), 3 weeks, 6 months)
- Change From Baseline in Mixed-Meal Tolerance Test (MMTT) Response - C-Peptide Area Under the Curve (AUC) at 3-Week and 6-Month Endpoints(Baseline (Week -1), 3 weeks, 6 months)
- Change From Baseline in Mixed Meal Tolerance Test (MMTT) Response - Ratio of Insulin Area Under the Curve (AUC)/Glucose Area Under the Curve (AUC) at 3-Week and 6-Month Endpoints(Baseline (Week -1), 3 weeks, 6 months)
- Change From Baseline in Mixed-Meal Tolerance Test (MMTT) Response - Glucagon Area Under the Curve (AUC) at 3-Week and 6-Month Endpoints(Baseline (Week -1), 3 weeks, 6 months)
- Change From Baseline in Mixed-Meal Tolerance Test (MMTT) Response - Glucagon-like Peptide-1 (GLP-1) Area Under the Cure (AUC) at 3-Week and 6-Month Endpoints(Baseline (Week -1), 3 weeks, 6 months)
- Change From Baseline in Mixed-Meal Tolerance Test (MMTT) Response - Post-Prandial Glucose at 3-Week and 6-Month Endpoints(Baseline (Week -1), 3 weeks, 6 months)
- Change From Baseline in Fasting Blood Glucose (FBG) at 4-Week and 6-Month Endpoints(Baseline (Week -1), 4 weeks, 6 months)
- Change From Baseline in Glycosylated Hemoglobin (HbA1C) Adjusted for Baseline Glycosylated Hemoglobin (HbA1c), C-Peptide Level, Homeostasis Model Assessment of Insulin Resistance (HOMA), Duration of Diabetes, and Body Mass Index (BMI) at 6-Month Endpoint(Baseline (Week -1), 6 months)
- Change From Baseline in MMTT Response (Postprandial Glucose, Glucose AUC, Insulin/c-Peptide Secretory Response, HOMA, GLP-1, Glucagon) Adjusted for Baseline HbA1c, C-Peptide Level, HOMA, Duration of Diabetes, Weight at Week 0, 3, Month 3.5, 6 Endpoints(Baseline (Week -1), Week 0, 3 weeks, 3.5 months, 6 months)
- Change From Baseline in Fasting Blood Glucose (FBG) Adjusted for Baseline HbA1c, C-Peptide Level, Homeostasis Model Assessment of Insulin Resistance, Duration of Diabetes, and Weight at 3-Week, 4-Week, 2-Month, 3.5-Month, 5-Month, and 6-Month Endpoints(Baseline (Week -1), 3 weeks, 4 weeks, 2 months, 3.5 months, 5 months, 6 months)
- Mean Change From Baseline in Weight at Week 0, Week 4, and 6-Month Endpoints(Baseline (Week -1), Week 0, 4 weeks, 6 months)
- Number of Participants With Antibodies to LY2428757(Baseline (Week -1) through 6 months)
- Number of Participants With Antibodies to TT223(Baseline (Week -1) through 6 months)
- Pharmacokinetics (PKs) of TT223, First Dose - Time of Maximum Observed Drug Concentration (Tmax)(0 (pre-dose), 0.33, 0.5, 1, 2, 3, 4, 6 hours)
- Pharmacokinetics (PKs) of TT223, First Dose - Maximum Observed Drug Concentration (Cmax)(0 (pre-dose), 0.33, 0.5, 1, 2, 3, 4, 6 hours)
- Pharmacokinetics (PKs) of TT223, First Dose - Half-Life (t1/2) Associated With the Terminal Rate Constant (λz) in Non-Compartmental Analysis(0 (pre-dose), 0.33, 0.5, 1, 2, 3, 4, 6 hours)
- Pharmacokinetics (PKs) of TT223, First Dose - Area Under the Curve (AUC)(0-infinity)(0 (pre-dose), 0.33, 0.5, 1, 2, 3, 4, 6 hours)
- Pharmacokinetics (PKs) of TT223, First Dose - Apparent Total Body Clearance of Drug Calculated After Extra-Vascular Administration (CL/F)(0 (pre-dose), 0.33, 0.5, 1, 2, 3, 4, 6 hours)
- Percentage of Participants With 2-Fold Elevation of Lipase and/or Amylase at Any Timepoint(Baseline (Week -1) through 6 months)
- Pharmacokinetics (PKs) of TT223, First Dose - Apparent Volume of Distribution During the Terminal Phase After Extra-Vascular Administration (Vz/F), Apparent Volume of Distribution at Steady-State After Extra-Vascular Administration (Vss/F)(0 (pre-dose), 0.33, 0.5, 1, 2, 3, 4, 6 hours)
- Pharmacokinetics (PKs) of TT223, 3-Week Time Point - Maximum Observed Drug Concentration (Cmax)(0 (pre-dose), 0.33, 0.5, 1, 2, 3, 4, 6 hours)
- Pharmacokinetics (PKs) of TT223, 3-Week Time Point - Time of Maximum Observed Drug Concentration (Tmax)(0 (pre-dose), 0.33, 0.5, 1, 2, 3, 4, 6 hours)
- Pharmacokinetics (PKs) of TT223, 3-Week Time Point - Half Life (t1/2)(0 (pre-dose), 0.33, 0.5, 1, 2, 3, 4, 6 hours)
- Pharmacokinetics (PKs) of TT223, 3-Week Time Point - Area Under Concentration Versus Time From Zero to Infinity (AUC[0-infinity])(0 (pre-dose), 0.33, 0.5, 1, 2, 3, 4, 6 hours)
- Pharmacokinetics (PKs) of TT223, 3-Week Time Point - Apparent Total Body Clearance of Drug Calculated After Extra-Vascular Administration (CL/F)(0 (pre-dose), 0.33, 0.5, 1, 2, 3, 4, 6 hours)
- Pharmacokinetics (PKs) of TT223, 3-Week Time Point - Apparent Volume of Distribution During the Terminal Phase After Extra-Vascular Administration (Vz/F), Apparent Volume of Distribution at Steady-State After Extra-Vascular Administration (Vss/F)(0 (pre-dose), 0.33, 0.5, 1, 2, 3, 4, 6 hours)
- Pharmacokinetics (PKs) of LY2428757, 3-Week Time Point - Maximum Observed Drug Concentration (Cmax)(0 (pre-dose))
- Visual Analog Scale (VAS) for Nausea(4 weeks, 6 months)
- Change From Baseline in Waist Circumference at 6-Month Endpoint(Baseline (Week -1), 6 months)
- 7-point Profile, Self-Monitored Blood Glucose (SMBG) Values(Baseline (Week -1), 4 weeks, 6 months)
- Change From Baseline in 7-Point Profile, Self-Monitored Blood Glucose (SMBG) at 4-Week and 6-Month Endpoints(Baseline (Week -1), 4 weeks, 6 months)
- Change From Baseline in Lipase at Week 0, Week 4, and 6-Month Endpoints(Baseline (Week -1), Week 0, 4 weeks, 6 months)
- Change From Baseline in Amylase at 6-Month Endpoint(Baseline (Week -1), 6 months)
- Percentage of Participants With Hypoglycemia(Baseline (Week -1) through 6 months)
- Number of Participants With Hypoglycemia(Baseline (Week -1) through 6 months)
- Number of Participants With Adjudicated and Confirmed Deaths and Non-Fatal Cardiovascular (CV) Events at Any Timepoint(Baseline (Week -1) through 6 months)
- Change From Baseline in Fasting Insulin at 4-Week and 6-Month Endpoints(Baseline (Week -1), 4 weeks, 6 months)
- Change From Baseline in Homeostatic Model Assessment (HOMA) at 3-Week and 6-Month Endpoints(Baseline (Week -1), 3 weeks, 6 months)
研究者
研究点 (1)
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