A 5-year Study to Compare the Durability of Glycemic Control of a Combination Regimen With Vildagliptin & Metformin Versus Standard-of-care Monotherapy With Metformin, Initiated in Treatment-naïve Patients With Type 2 Diabetes Mellitus
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 2,004
- 试验地点
- 1
- 主要终点
- Time to Initial Treatment Failure
研究概览
简要总结
The purpose of this study was to determine whether the initiation of a vildagliptin plus metformin combination regimen would result in more durable glycemic control than metformin monotherapy in treatment-naïve patients with type-2 diabetes mellitus (T2DM).
详细描述
This was a multi-center, double-blind, placebo-controlled, 2-arm, parallel group study with a run-in period and up to 5 years treatment period. Following a screening visit (Visit 1) and a screening period of up to 2 weeks, treatment-naïve patients, meeting all eligibility criteria entered the run-in period at Visit 2.
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Run-in period: At Visit 2, in all eligible patients, metformin treatment was initiated and/or up-titrated. At the end of the 3-week run-in period, patients who were able to tolerate a total dose of at least 1000 mg and up to 2000 mg daily proceeded to randomization and started in Period 1.
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Period 1 (vildagliptin/metformin combination versus metformin): At Visit 3, patients were randomized 1:1 to one of the following study regimens:
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Metformin up to 1000 mg bid plus vildagliptin 50mg bid or
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Metformin up to 1000 mg bid plus matching placebo bid
The duration of Period 1 could differ between patients depending on the time when the second of two HbA1c measurements taken at two consecutive visits after randomisation confirmed HbA1c ≥ 7.0%.
• Period 2 (vildagliptin/metformin combination versus vildagliptin add-on to metformin): In the case of two consecutive HbA1c measurements ≥7.0% from two consecutive study visits during Period 1, patients who were randomised to the placebo arm in Period 1 received vildagliptin 50 mg bid. Patients who were randomised to the active vildagliptin 50 mg bid arm in Period 1 continued to receive vildagliptin 50 mg bid. All patients continued to take their metformin dose unchanged. Period 2 remained masked to the patient and both patients and investigators remained masked to the treatment allocation in Period 1.
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Type 2 Diabetes Mellitus (T2DM) diagnosed ≤ 24 months ago
- •glycosylated hemoglobin (HbA1c) ≥6.5% and ≤7.5% at Visit 1
- •Treatment-naïve.
- •Body mass index (BMI) ≥22 and ≤40 kg/m2 at Visit 1
排除标准
- •Pregnant or nursing (lactating) women
- •Fasting plasma glucose (FPG) ≥ 270 mg/dL (≥ 15.0 mmol/L)
- •Previous or current participation in any vildagliptin clinical study.
- •History of hypersensitivity to dipeptidyl peptidase-4 (DPP-4) inhibitors.
- •Concurrent medical condition that may interfere with the interpretation of efficacy and safety data during the study.
- •Donation of blood or significant blood loss equaling to at least one unit of blood within the past 2 weeks of start of study or a blood transfusion within the past 12 weeks or planned regular transfusions during the study period.
研究组 & 干预措施
Vilda 50mg bid + metformin
Metformin + vildagliptin
干预措施: vildagliptin (Drug)
Vilda 50mg bid + metformin
Metformin + vildagliptin
干预措施: Metformin (Drug)
Placebo + metformin
Metformin + Placebo of vildagliptin
干预措施: Placebo of vildagliptin (Drug)
Placebo + metformin
Metformin + Placebo of vildagliptin
干预措施: Metformin (Drug)
结局指标
主要结局
Time to Initial Treatment Failure
时间窗: Visit 4 (Week 13) up to End of Study (Study Drug Discontinuation or Premature Subject Discontinuation)
Treatment failure was defined as two consecutive scheduled visits with HbA1c \>= 7.0% (starting from 13 weeks after randomization) and the time to treatment failure was the number of days from randomization to the second of the consecutive scheduled visits. Participants who discontinued the study for any reason during Period 1 were censored at the date of discontinuation. Participants who remained under the threshold (or whose measurement above the threshold was not confirmed at next scheduled visit) were censored at the date of last study visit.
次要结局
- Rate of Loss in Glycemic Control During Period 1(Visit 5 (Week 26) to End of Period 1)
- Rate of Loss in Glycemic Control in HbA1c Over Time During Period 2(From 26 weeks after start of Period 2 to end of Period 2)
- Rate of Loss in Glycemic Control in Fasting Plasma Glucose (FPG) During Period 1(Visit 5 (Week 26) to End of Period 1)
- Rate of Loss in Glycemic Control in Fasting Plasma Glucose (FPG) Over Time During Period 2(From 26 weeks after start of Period 2 to end of Period 2)
- Rate of Loss of Beta Cell Function From Baseline to End of Study(Visit 4 (Week 13), End of Period 1, End of Period 2, End of Study (Study Drug Discontinuation or Premature Subject Discontinuation))
- Rate of Change in Insulin Sensitivity From Baseline to End of Study(Visit 4 (Week 13), End of Period 1, End of Period 2, End of Study (Study Drug Discontinuation or Premature Subject Discontinuation))
- Percentage of Participants With Adverse Events, Serious Adverse Events and Death(From first dose of study treatment until End of Study (Study Drug Discontinuation or Premature Subject Discontinuation))