An International, Multicenter, Randomized, Double-blind, Placebo-controlled, Phase 3 Study to Determine the Efficacy and Safety of SYR-322 When Used 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
- 506
- 主要终点
- Change From Baseline in Glycosylated Hemoglobin (HbA1c)
研究概览
简要总结
The purpose of the study is to determine the efficacy of alogliptin compared to placebo when given alone or as add-on therapy to metformin or add-on to pioglitazone (with or without metformin).
详细描述
Diabetes is a chronic illness associated with microvascular complications such as nephropathy (kidney disease), retinopathy (eye damage) and neuropathy (nervous system damage). Diabetes is also associated with macrovascular complications including cardiovascular disease (heart disease), stroke and peripheral vascular disease (narrowing or blockage of blood vessels). These complications are associated with reduced quality of life and increased morbidity and mortality.
Takeda is developing SYR-322 (alogliptin) for improvement of glycemic control in patients with Type 2 diabetes mellitus.
Evaluations of alogliptin and its clinical efficacy have been conducted in multiple countries including the United States and Japan. This study will be conducted as a multi-center clinical trial in order to validate the efficacy and safety of alogliptin on type 2 diabetes population within Asia.
Participants who qualified for the study were stratified into 1 of the 3 therapy groups based upon their background antidiabetic therapy before being randomized 1:1 to receive either alogliptin 25 mg once daily or matching placebo once daily.
- Monotherapy group - patients who had been treated with diet and exercise for at least 2 months prior to screening.
- Add-on to metformin therapy group - patients who had been treated with metformin for at least 3 months and at a stable dose (≥1000 mg/day) for at least 8 weeks prior to screening.
- Add-on to pioglitazone therapy group - patients who had been treated with a stable dose of pioglitazone alone or in combination with metformin at a stable dose for at least 8 weeks prior to screening.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Has a historical diagnosis of Type 2 Diabetes Mellitus.
- •Has a body mass index between acceptable range.
- •Is experiencing inadequate glycemic control.
- •Body weight keeps constant.
- •Females of childbearing potential and males who are sexually active agree to use routinely adequate contraception from signing of informed consent throughout the duration of the study and for 30 days after last dose.
排除标准
- •Has participated in another clinical study within the past 90 days or has received any investigational compound within 30 days prior to randomization.
- •Has a systolic blood pressure beyond the acceptable range at Screening visit.
- •Has New York Heart Association Class III or IV heart failure regardless of therapy.
- •Has any major illness or debility that in the investigator's opinion prohibits the subject from completing the study.
- •Has a history of hypersensitivity or allergies to any DPP-4 inhibitor.
研究组 & 干预措施
Placebo
Participants received alogliptin placebo-matching tablets, orally once daily for up to 16 weeks.
干预措施: Placebo to alogliptin (Drug)
Alogliptin Monotherapy
Participants received alogliptin 25 mg tablets, orally, once daily for up to 16 weeks.
干预措施: Alogliptin (Drug)
Metformin
Participants continued to receive their stable dose of metformin (≥1000 mg/day) and also received alogliptin placebo-matching tablets, orally once daily for up to 16 weeks.
干预措施: Placebo to alogliptin (Drug)
Metformin
Participants continued to receive their stable dose of metformin (≥1000 mg/day) and also received alogliptin placebo-matching tablets, orally once daily for up to 16 weeks.
干预措施: Metformin (Drug)
Metformin + Alogliptin Add-on Therapy
Participants continued to receive their stable dose of metformin (≥1000 mg/day) and also received alogliptin 25 mg tablets, orally, once daily for up to 16 weeks.
干预措施: Alogliptin (Drug)
Metformin + Alogliptin Add-on Therapy
Participants continued to receive their stable dose of metformin (≥1000 mg/day) and also received alogliptin 25 mg tablets, orally, once daily for up to 16 weeks.
干预措施: Metformin (Drug)
Pioglitazone
Participants continued to receive their stable dose of pioglitazone with or without metformin, and also received alogliptin placebo-matching tablets, orally once daily for up to 16 weeks.
干预措施: Placebo to alogliptin (Drug)
Pioglitazone
Participants continued to receive their stable dose of pioglitazone with or without metformin, and also received alogliptin placebo-matching tablets, orally once daily for up to 16 weeks.
干预措施: Pioglitazone (Drug)
Pioglitazone + Alogliptin Add-on Therapy
Participants continued to receive their stable dose of pioglitazone with or without metformin and also received alogliptin, 25 mg tablets orally once daily for up to 16 weeks.
干预措施: Alogliptin (Drug)
Pioglitazone + Alogliptin Add-on Therapy
Participants continued to receive their stable dose of pioglitazone with or without metformin and also received alogliptin, 25 mg tablets orally once daily for up to 16 weeks.
干预措施: Pioglitazone (Drug)
结局指标
主要结局
Change From Baseline in Glycosylated Hemoglobin (HbA1c)
时间窗: Baseline and Week 16.
The change from Baseline in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at Week 16. Least squares means are derived from an analysis of covariance (ANCOVA) model with treatment as a fixed effect, and baseline HbA1c as a covariate for the monotherapy, baseline HbA1c with baseline metformin dose as covariates for the metformin therapy, baseline HbA1c with baseline metformin therapy status and baseline pioglitazone dose as covariates for the pioglitazone therapy.
次要结局
- Change From Baseline in HbA1c Over Time(Baseline and Weeks 4, 8 and 12.)
- Change From Baseline in Fasting Plasma Glucose Over Time(Baseline and Weeks 4, 8, 12 and 16.)
- Percentage of Participants With Marked Hyperglycemia(Randomization to Week 16.)
- Change From Baseline in Body Weight(Baseline and Weeks 8 and 16.)
- Percentage of Participants With HbA1c ≤6.5% at Week 16(Week 16)
- Percentage of Participants With HbA1c ≤7.0% at Week 16(Week 16)
- Percentage of Participants With HbA1c ≤7.5% at Week 16(Week 16)
- Percentage of Participants With a Decrease in HbA1c ≥ 0.5%(Baseline and Week 16)
- Percentage of Participants With a Decrease in HbA1c ≥1.0%(Baseline and Week 16)
- Percentage of Participants With a Decrease in HbA1c ≥1.5%(Baseline and Week 16.)
- Percentage of Participants With a Decrease in HbA1c ≥2.0%(Baseline and Week 16.)