A Multicenter, Double-Blind Study to Determine the Efficacy and Safety of SYR-322 Plus Pioglitazone HCl (Actos®), SYR-322 Alone or Pioglitazone HCl Alone in Subjects With Type 2 Diabetes
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 655
- 主要终点
- Change From Baseline to Week 26 in Glycosylated Hemoglobin (HbA1c)
研究概览
简要总结
The purpose of this study is to evaluate the combination of alogliptin, once daily (QD), and pioglitazone in patients with type 2 diabetes mellitus who are inadequately controlled with diet and exercise alone.
详细描述
There are approximately 19 million people in the United States who have been diagnosed with diabetes mellitus, of which 90% to 95% is type 2. The prevalence of type 2 diabetes varies among racial and ethnic populations and has been shown to correlate with age, obesity, family history, history of gestational diabetes, and physical inactivity. Over the next decade, a marked increase in the number of adults with diabetes mellitus is expected, placing an ever-increasing burden on families and the health care system.
Current pharmacologic interventions for type 2 diabetes mellitus include a diverse range of antidiabetic medications with different mechanisms of action including insulin and insulin analogues, sulfonylureas, metformin, meglitinides, thiazolidinediones, inhibitors of alpha- glucosidase, analogs of glucagon-like peptide-1, and synthetic analogues of human amylin. Despite the variety of medications, many have clinically important or potentially life-threatening side effects, restricted use in many subpopulations, concerns with long-term tolerability, and challenges related to compliance due to side effects and route of administration. All of these reasons contribute to the difficulties patients have reaching the target glycosylated hemoglobin level less than 7%.
SYR-322 (alogliptin) is a selective, orally available inhibitor of the dipeptidyl peptidase-4 enzyme. Dipeptidyl peptidase-4 enzyme is thought to be primarily responsible for the in vivo degradation of 2 peptide hormones released in response to nutrient ingestion, namely glucagon-like peptide-1 and glucose-dependent insulinotropic peptide. Both peptides exert important effects on islet beta cells to stimulate glucose-dependent insulin secretion as well as regulating beta cell proliferation and cytoprotection. Glucagon-like peptide-1, but not glucose-dependent insulinotropic peptide, inhibits gastric emptying, glucagon secretion, and food intake. Glucose-dependent insulinotropic peptide has been shown to enhance insulin secretion by direct interaction with a glucose-dependent insulinotropic peptide -specific receptor on islet beta cells. The glucose-lowering actions of glucagon-like peptide-1, but not glucose-dependent insulinotropic peptide, are preserved in patients with type 2 diabetes mellitus.
Pioglitazone (ACTOS®) is a thiazolidinedione developed by Takeda Chemical Industries, Ltd. (Osaka, Japan) that is approved for the treatment of type 2 diabetes mellitus. Pioglitazone is a selective peroxisome proliferator-activated receptor-gamma agonist that decreases insulin resistance in the periphery and liver resulting in increased insulin-dependent glucose disposal and decreased hepatic glucose output.
As the rate of newly diagnosed cases of type 2 diabetes mellitus continues to grow, so does the need for products that will provide better glycemic control and improved safety and tolerability. Alogliptin and pioglitazone have complementary actions. Alogliptin inhibits the degradation of glucagon-like peptide-1 by inhibiting the enzyme dipeptidyl peptidase IV, thus augmenting glucose-dependent insulin secretion while pioglitazone is a peripheral and hepatic insulin sensitizer. Given the complementary mechanisms of action of alogliptin (stimulates insulin secretion) and pioglitazone (enhances insulin sensitivity), the addition of combination therapy in treatment naïve type 2 diabetes patients may potentially allow the patients to reach and maintain their glycosylated hemoglobin goal more effectively.
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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Alogliptin 25 mg QD
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.
干预措施: Alogliptin (Drug)
Alogliptin 25 mg QD
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone placebo-matching tablets, orally, once daily for up to 26 weeks.
干预措施: Placebo (Drug)
Pioglitazone 30 mg QD
Pioglitazone 30 mg, tablets, orally, once daily and alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks.
干预措施: Pioglitazone (Drug)
Pioglitazone 30 mg QD
Pioglitazone 30 mg, tablets, orally, once daily and alogliptin placebo-matching tablets, orally, once daily for up to 26 weeks.
干预措施: Placebo (Drug)
Alogliptin 25 mg QD+ Pioglitazone 30 mg QD
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
干预措施: Alogliptin (Drug)
Alogliptin 25 mg QD+ Pioglitazone 30 mg QD
Alogliptin 25 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
干预措施: Pioglitazone (Drug)
Alogliptin 12.5 mg QD + Pioglitazone 30 mg QD
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
干预措施: Alogliptin (Drug)
Alogliptin 12.5 mg QD + Pioglitazone 30 mg QD
Alogliptin 12.5 mg, tablets, orally, once daily and pioglitazone 30 mg, tablets, orally, once daily for up to 26 weeks.
干预措施: Pioglitazone (Drug)
结局指标
主要结局
Change From Baseline to Week 26 in Glycosylated Hemoglobin (HbA1c)
时间窗: Baseline and Week 26
The change from Baseline to Week 26 in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound).
次要结局
- Change From Baseline in HbA1c Over Time(Baseline and Weeks 4, 8, 12, 16 and 20.)
- Change From Baseline in Fasting Plasma Glucose Over Time(Baseline and Weeks 1, 2, 4, 8, 12, 16, 20 and 26.)
- Percentage of Participants With Marked Hyperglycemia(Weeks 1, 2, 4, 8, 12, 16, 20 and 26.)
- Change From Baseline in High-Density Lipoprotein Cholesterol(Baseline and Weeks 4, 8, 12, 16, 20 and 26.)
- Percentage of Participants Meeting Rescue Criteria(Weeks 4, 8, 12, 16, 20 and 26.)
- Percentage of Participants With Glycosylated Hemoglobin Less Than or Equal to 6.5%(Week 26)
- Percentage of Participants With Glycosylated Hemoglobin Less Than or Equal to 7.0%(Week 26)
- Percentage of Participants With Glycosylated Hemoglobin Less Than or Equal to 7.5%(Week 26)
- Percentage of Participants With a Decrease in Glycosylated Hemoglobin Greater Than or Equal to 0.5%(Baseline and Week 26)
- Percentage of Participants With a Decrease in Glycosylated Hemoglobin Greater Than or Equal to 1.0%(Baseline and Week 26)
- Percentage of Participants With a Decrease in Glycosylated Hemoglobin Greater Than or Equal to 1.5%.(Baseline and Week 26)
- Percentage of Participants With a Decrease in Glycosylated Hemoglobin Greater Than or Equal to 2.0%(Baseline and Week 26)
- Change From Baseline in Fasting Proinsulin(Baseline and Weeks 4, 8, 12, 16, 20 and 26.)
- Change From Baseline in Insulin(Baseline and Weeks 4, 8, 12, 16, 20 and 26.)
- Change From Baseline in Proinsulin/Insulin Ratio(Baseline and Weeks 4, 8, 12, 16, 20 and 26.)
- Change From Baseline in C-peptide Levels(Baseline and Weeks 4, 8, 12, 16, 20 and 26.)
- Change From Baseline in Calculated Homeostatic Model Assessment Insulin Resistance(Baseline and Weeks 12 and 26.)
- Change From Baseline in Homeostatic Model Assessment Beta Cell Function(Baseline and Weeks 12 and 26.)
- Change From Baseline in Body Weight(Baseline and Weeks 8, 12, 20 and 26.)
- Change From Baseline in Total Cholesterol Level(Baseline and Weeks 4, 8, 12, 16, 20 and 26.)
- Change From Baseline in Low-Density Lipoprotein Cholesterol(Baseline and Weeks 4, 8, 12, 16, 20 and 26.)
- Change From Baseline in Triglyceride Levels(Baseline and Weeks 4, 8, 12, 16, 20 and 26.)
- Change From Baseline in Free Fatty Acids(Baseline and Weeks 12 and 26.)
- Change From Baseline in Plasminogen Activator Inhibitor-1(Baseline and Weeks 12 and 26.)
- Change From Baseline in High-sensitivity C-Reactive Protein(Baseline and Weeks 12 and 26.)
- Change From Baseline in Adiponectin(Baseline and Weeks 12 and 26.)
- Change From Baseline in Apolipoprotein A1(Baseline and Weeks 12 and 26.)
- Change From Baseline in Apolipoprotein A2(Baseline and Weeks 12 and 26.)
- Change From Baseline in Apolipoprotein B(Baseline and Weeks 12 and 26.)
- Change From Baseline in Apolipoprotein C-III(Baseline and Weeks 12 and 26.)
- Change From Baseline in Nuclear Magnetic Resonance Lipid Fractionation Total Triglycerides(Baseline and Weeks 12 and 26.)
- Change From Baseline in Very Low Density Lipoprotein (VLDL) / Chylomicron Particles(Baseline and Weeks 12 and 26.)
- Change From Baseline in VLDL / Chylomicron Triglycerides(Baseline and Weeks 12 and 26.)
- Change From Baseline in VLDL Particles(Baseline and Weeks 12 and 26.)
- Change From Baseline in Mean VLDL Particle Size(Baseline and Weeks 12 and 26.)
- Change From Baseline in Intermediate Density Lipoprotein (IDL) Particles(Baseline and Weeks 12 and 26.)
- Change From Baseline in Low Density Lipoprotein (LDL) Particles(Baseline and Weeks 12 and 26.)
- Change From Baseline in Mean LDL Particle Size(Baseline and Weeks 12 and 26.)
- Change From Baseline in High Density Lipoprotein (HDL) Particles(Baseline and Weeks 12 and 26.)
- Change From Baseline in Mean HDL Particle Size(Baseline and Weeks 12 and 26.)