A Single-site, Randomized, Double-blind, Placebo-controlled, Parallel-group, Stepped Glucose Clamp Study to Assess the Effects of Albiglutide on Counter-regulatory Hormone Responses and Recovery From Hypoglycemia in Subjects With Type 2 Diabetes Mellitus.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 44
- 试验地点
- 1
- 主要终点
- Glucagon Concentration (Nanomoles Per Liter [Nmol/L]) During the Hypoglycemic Periods of the Glucose Clamp Procedure
研究概览
简要总结
This is a stepped glucose clamp study designed to investigate the effect of treatment with albiglutide on counter-regulatory hormone responses and recovery from hypoglycemia in subjects with Type 2 diabetes mellitus. A single dose of albiglutide or placebo will be given prior to a stepped hyper- and hypoglycemic clamp. The goal of this study is to demonstrate that albiglutide increases insulin secretion and decreases glucagon levels in a glucose-dependent manner.
详细描述
This is a Phase II, single-site, randomized, double-blind, parallel-group, placebo-controlled, stepped glucose clamp study designed to investigate the effect of treatment with albiglutide on counter-regulatory hormone responses and recovery from hypoglycemia in subjects with Type 2 diabetes mellitus. A single dose of albiglutide or placebo will be given 3 days before employing a stepped hyper- and hypoglycemic clamp. The goal of this study is to demonstrate that albiglutide increases insulin secretion and decreases glucagon levels in a glucose-dependent manner. In particular, this study is being conducted to ensure that albiglutide does not impair counter-regulatory responses during hypoglycemia.
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 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Historical diagnosis of type 2 diabetes mellitus for at least 6 months and less than 10 years before Screening
- •HbA1c <10% at Screening for subjects who do not require washout of existing OAD or <9% at Screening for subjects who do require washout from existing OAD
- •Body mass index in range 28 kg/m2 to40 kg/m2
排除标准
- •History of pancreatitis or current ongoing symptomatic biliary disease or pancreatitis
- •History of significant gastrointestinal surgery,
- •History of significant cardiovascular disease
- •History of a seizure disorder
- •Documented hypertension or hypotension
- •Use of oral antidiabetic agents, except for metformin, within 14 days before investigational product administration.
- •Current hepatic disease or abnormal liver function tests
- •Positive test result for hepatitis B, hepatitis C, or human immunodeficiency virus infection 1 or 2
- •History of regular alcohol consumption (exceeding 7 drinks/week for women or 14 drinks/week for men)
- •Female subject is pregnant (confirmed by laboratory testing), lactating, or less than 6 weeks postpartum
- •Known allergy to any GLP-1 analog or excipients of albiglutide, Baker's yeast, or insulin
- •History of type 1 diabetes,
- •Prior exposure to GLP-1 agents, including albiglutide
- •Blood donation over 500 mL within 8 weeks before Screening
研究组 & 干预措施
placebo
single dose of placebo
干预措施: placebo (Biological)
albiglutide
single dose of albiglutide
干预措施: albiglutide (Biological)
结局指标
主要结局
Glucagon Concentration (Nanomoles Per Liter [Nmol/L]) During the Hypoglycemic Periods of the Glucose Clamp Procedure
时间窗: Day 4
Plasma glucagon levels were measured for the estimation of glucagon secretion during the hypoglycemic periods. Glucagon response was measured at each clamped glucose concentration: 9 millimoles per liter (mmol/L) (0 hour \[hr\], 1hr, 1 hr 15 minutes \[min\]), 5 mmol/L (1 hr 45 min, 2 hr), 4 mmol/L (2 hr 45 min, 3 hr), 3.3 mmol/L (3 hr 30 min, 3 hr 45 min), and 2.8 mmol/L (4 hr 15 min, 4 hr 30 min), and clamp released (4 hr 45 min, 5 hr, 5 hr 15 min, 5 hr 30 min). Repeated-measures analysis of variance was performed on non-transformed pharmacodynamic parameters using a model with treatment, time, and treatment-by-time as fixed effects, and participant as a random effect. Values below the lower limit of quantification (0.03780 nmol/L) were set to the quantification limit for summary.
次要结局
- Cortisol Values During the Glucose Clamp Period(Day 4)
- Insulin Secretion Rate (Measured by Mathematical Analysis of C-peptide Concentrations) During the Glucose Clamp Period(Day 4)
- Epinephrine Values During the Glucose Clamp Period(Day 4)
- Norepinephrine Values During the Glucose Clamp Period(Day 4)
- Growth Hormone Values During the Glucose Clamp Period(Day 4)
- C-peptide Values During the Glucose Clamp Period(Day 4)
- Recovery Time of Plasma Glucose Levels to >=3.9 mmol/L (>=70 mg/dL) From the Hypoglycemic Clamp Level of 2.8 Nmol/L (50.4 mg/dL)(Day 4)
- Number of Participants With Any Treatment-emergent Serious Adverse Event (SAE) and Treatment-emergent Non-serious Adverse Event (AE) During the Clamp Period(From the time the participant consented to participate in the study through the end of the study, or the final follow-up visit for participants who discontinued active participation in the study (up to 8 study weeks))
- Insulin Values During the Glucose Clamp Period(Day 4)
- Average Albiglutide Concentration on the Day of the Clamp Procedure(Day 4)