Assessment of Dose-Dependent Effects of LY2189265 on Glycemic Control in Patients With Type 2 Diabetes Treated Only With Lifestyle Interventions
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 167
- 试验地点
- 1
- 主要终点
- Change From Baseline in Glycosylated Hemoglobin (HbA1c)
研究概览
简要总结
This is a study to demonstrate that different doses of once-weekly LY2189265 injected subcutaneously will have dose proportional effect on hemoglobin A1c (HbA1c) at 12 weeks in participants with type 2 diabetes mellitus.
详细描述
Participants in the trial will be randomized to one of the LY2189265 doses (4 doses are planned, range 0.1-1.5 milligram [mg]) or placebo. The main purpose is to assess dose-dependent effect of this new compound on blood glucose over a period of 12 weeks. Therefore, glycosylated hemoglobin (HbA1c) is chosen as the primary efficacy measure. Several other attributes of glycemic control and endocrine function of pancreas will be assessed as secondary objectives. These secondary objectives will be used to compare the effect of the experimental compound and placebo. Since LY2189265 is in early phase of development, comprehensive safety assessment is planned to learn more about possible side-effects and to establish benefit/risk profile of individual doses of the drug. The trial is organized in four phases: screening, lead-in period to establish baseline status of participants in each group, treatment period during which participants will be randomized into 1 of 5 groups (4 will receive one of the LY2189265 doses, 1 group will receive placebo), and safety follow up. Maximum of 9 study visits are planned. Study drug (LY2189265 or placebo) will be administered once weekly via subcutaneous (SC) injections. Rescue intervention was allowed after randomization for those participants whose hyperglycemia reached pre-defined unacceptable high values. Participants on rescue therapy remained in the study and continued to receive study drug. 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.
A 3-mg LY2189265 dose was discontinued and replaced with the 1.5 mg dose based on dose finding Study H9X-MC-GBCF; NCT00734474. Except where noted, data summaries from the 3 discontinued 3-mg LY2189265 participants (n=3) are not included due to the small number of participants and the short treatment duration.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diabetes mellitus, type 2
- •Treatment regimens: diet and exercise only or are taking metformin as monotherapy and are willing to discontinue this medication
- •Have completed at least 8 weeks of wash-out prior to randomization (if on metformin therapy at screening)
- •Have a qualifying glycosylated hemoglobin (HbA1c) value, as determined by the central laboratory: at screening (for diet and exercise only ≥7.0% to ≤9.5%; for metformin monotherapy >6.5% to ≤9.0%) and at time of randomization for all participants ≥6.5% to ≤9.5%
- •Females of childbearing potential must test negative for pregnancy and agree to use a reliable birth control method
- •Have a body mass index (BMI) between 23 and 40 kilograms/meter squared (kg/m^2), inclusive, for participants who are native to, and reside in, South and/or East Asia; all other participants must have a BMI between 25 and 40 kg/m^2, inclusive.
- •Stable weight for 3 months prior to screening
排除标准
- •Diabetes mellitus, type 1
- •Taking any glucose-lowering oral agents other than metformin within 3 months prior to screening
- •Use of glucagon-like peptide-1 (GLP-1) analog (for example, exenatide) within 6 months prior to screening or being treated within insulin (with the exception of short-term management of acute conditions that occurred more than 3 months immediately prior to screening)
- •Use of medications (prescription or over-the counter) to promote weight loss
- •Chronic (>2 weeks) use of systemic glucocorticoid therapy
- •Gastric emptying abnormality, history of bariatric surgery or chronic use of drugs that affect gastrointestinal motility
- •Use of central nervous system (CNS) stimulant (for example, Ritalin-sustained release [SR])
- •Cardiovascular event within 6 months prior to screening
- •Poorly controlled hypertension (determined by a mean seated systolic blood pressure (BP) ≥160 millimeters of mercury (mmHg) or mean seated diastolic BP ≥95 mmHg at screening or randomization)
- •Electrocardiogram (ECG) reading considered outside the normal limits by the investigator and relevant for interpretation or indicating cardiac disease
- •Liver disease, hepatitis, chronic hepatitis, or alanine transaminase levels >3.0 times upper limit of normal
- •Clinical signs or symptoms of pancreatitis or history of chronic or acute pancreatitis at time of screening
- •Amylase ≥3 times the upper limit of normal and/or lipase ≥2 times upper limit of normal which are determined by central labs at the time of screening
- •Serum creatinine ≥1.5 milligrams per deciliter (mg/dL) for men or ≥1.4 mg/dL for women or a creatinine clearance <60 milliliter (mL)/minute which are determined by central labs at the time of screening
- •Uncontrolled diabetes (defined as 2 or more episode of hyperosmolar state requiring hospitalization in the 6 months prior to screening)
- •Significant active, uncontrolled endocrine or autoimmune abnormality
- •History of a transplanted organ (corneal transplants are allowed)
- •Active or untreated malignancy (other than basal or squamous cell skin cancer, in situ carcinomas of the cervix, or in situ prostate cancer) for less than 5 years
- •Have any other condition, in the opinion of the investigator, that may preclude the participant from following or completing the protocol
- •Investigator site personnel directly affiliated with this study and/or their immediate families (spouse, parent, child, or sibling, whether biological or legally adopted)
- •Sponsor employees
- •Received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry
- •Participated in an interventional medical, surgical, or pharmaceutical study within 30 days prior to entry into the study
- •Have previously completed or withdrawn from this study after providing informed consent
研究组 & 干预措施
0.1 milligram (mg) LY2189265
LY2189265: 0.1 milligram (mg), subcutaneous (SC), once weekly (QW)
干预措施: LY2189265 and Lifestyle Measures (Drug)
0.5 milligram (mg) LY2189265
LY2189265: 0.5 milligram (mg), subcutaneous (SC), once weekly (QW)
干预措施: LY2189265 and Lifestyle Measures (Drug)
1.0 milligram (mg) LY2189265
LY2189265: 1.0 milligram (mg), subcutaneous (SC), once weekly (QW)
干预措施: LY2189265 and Lifestyle Measures (Drug)
1.5 milligram (mg) LY2189265
LY2189265: 1.5 milligram (mg), subcutaneous (SC), once weekly (QW)
干预措施: LY2189265 and Lifestyle Measures (Drug)
Placebo
Placebo: subcutaneous (SC) once weekly (QW)
干预措施: Placebo solution and Lifestyle Measures (Drug)
结局指标
主要结局
Change From Baseline in Glycosylated Hemoglobin (HbA1c)
时间窗: Baseline, 12 weeks
Least Squares (LS) means of change from baseline for glycosylated hemoglobin (HbA1c) were calculated using mixed model repeated measures (MMRM) with pre-study therapy, country, dose, visit, and dose-by-visit interaction as fixed effects and baseline HbA1c as covariate.
次要结局
- Change From Baseline in Daily Mean Blood Glucose Values From the 7-point Self Monitored Blood Glucose (SMBG) Profiles(Baseline, 12 weeks)
- Change From Baseline in Beta-cell Function (HOMA2-%B)(Baseline, 12 weeks)
- Change From Baseline in Insulin Sensitivity (HOMA2-%S)(Baseline, 12 weeks)
- Change From Baseline in Electrocardiograms (ECGs) - Fridericia-corrected QT (QTcF) and PR Interval(Baseline, 12 weeks)
- Change From Baseline in Electrocardiograms (ECGs) - Heart Rate(Baseline, 12 weeks)
- Change From Baseline in Pulse Rate(Baseline, 12 weeks)
- Change From Baseline in Blood Pressure (BP)(Baseline, 12 weeks)
- Number of Participants With Self-reported Hypoglycemic Events(Baseline through 12 weeks)
- Change From Baseline in Glycosylated Hemoglobin (HbA1c)(Baseline, 4 weeks, 8 weeks)
- Change From Baseline in Fasting Blood Glucose(Baseline, 12 weeks)
- Percentage of Participants Who Achieve Glycosylated Hemoglobin (HbA1c) <7% or ≤6.5%(12 weeks)
- Rate of Self-reported Hypoglycemic Events(Baseline through 12 weeks)
- Treatment Emergent Adverse Events(Baseline through 12 weeks)
- Change From Baseline in Body Weight(Baseline, 12 weeks)
- Antibody Production and Effects to LY2189265(Baseline, 4 weeks, 12 weeks, 16 weeks)
- Collection and Evaluation of Plasma Levels (Pharmacokinetics [PK]) of LY2189265(4 weeks, 8 weeks, 12 weeks)