A Phase 3, Randomized, Double-blind, Placebo-controlled, 26-week Multicenter Study With a 26-Week Extension to Evaluate the Efficacy and Safety of Ertugliflozin Monotherapy in the Treatment of Subjects With Type 2 Diabetes Mellitus and Inadequate Glycemic Control Despite Diet and Exercise
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 461
- 主要终点
- Percentage of Participants Experiencing An Adverse Event (AE)
研究概览
简要总结
This trial will evaluate the efficacy and safety of ertugliflozin monotherapy in the treatment of participants with type 2 diabetes mellitus (T2DM) and inadequate glycemic control on diet and exercise. This trial consists of a run-in period of 3 to 11 weeks, a 26-week placebo-controlled treatment period (Phase A), and a 26-week active treatment period (Phase B). The primary hypotheses of the trial are that at Week 26, the mean reduction from baseline in hemoglobin A1c (A1C) for 15 mg ertugliflozin is greater than that for placebo and the mean reduction from baseline in A1C for 5 mg ertugliflozin is greater than that for placebo.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of T2DM in accordance to American Diabetes Association guidelines
- •Participants with no prior allowable oral anti-hyperglycemic agents (AHA) for at least 8 weeks prior to study participation or participants on a single allowable oral AHA at the start of study participation
- •Participants on a single allowable AHA must be willing to discontinue this medication at the Screening Visit (S2) and remain off this medication for the duration of the trial. Allowable oral AHAs for discontinuation are metformin, sulfonylureas, dipeptidyl peptidase-4 (DPP-4) inhibitors, glinides or alpha-glucosidase inhibitors.
排除标准
- •History of myocardial infarction, unstable angina, arterial revascularization, stroke, transient ischemic attack, or New York Heart Association (NYHA) functional class III-IV heart failure within 3 months of study participation
- •A clinically significant electrocardiogram abnormality
- •A history of malignancy ≤5 years prior to study participation, except for adequately treated basal or squamous cell skin cancer or in situ cervical cancer
- •A known hypersensitivity or intolerance to any sodium-glucose co-transporter 2 (SGLT2) inhibitor or metformin
- •On a blood pressure or lipid altering medication that have not been on a stable dose for at least 4 weeks prior to study participation
- •A surgical procedure within 4 weeks prior to study participation or planned major surgery during the trial
- •Donation of blood or blood products within 6 weeks of study participation or plans to donate blood or blood products at any time during the trial
- •Pregnant or breast-feeding, or is expecting to conceive during the trial, including 14 days following the last dose of study drug
研究组 & 干预措施
Ertugliflozin 5 mg/Ertugliflozin 5 mg
Phase A: Ertugliflozin 5 mg administered once daily for 26 weeks. Participants requiring rescue therapy will receive open-label metformin. Phase B: Ertugliflozin 5 mg administered once daily for 26 weeks. Participants not rescued with metformin in Phase A, will receive placebo to metformin. Participants rescued with metformin in Phase A will continue to receive metformin. Participants requiring rescue therapy during Phase B will receive open-label glimepiride.
干预措施: Ertugliflozin 5 mg (Drug)
Ertugliflozin 5 mg/Ertugliflozin 5 mg
Phase A: Ertugliflozin 5 mg administered once daily for 26 weeks. Participants requiring rescue therapy will receive open-label metformin. Phase B: Ertugliflozin 5 mg administered once daily for 26 weeks. Participants not rescued with metformin in Phase A, will receive placebo to metformin. Participants rescued with metformin in Phase A will continue to receive metformin. Participants requiring rescue therapy during Phase B will receive open-label glimepiride.
干预措施: Placebo to Ertugliflozin (Drug)
Ertugliflozin 5 mg/Ertugliflozin 5 mg
Phase A: Ertugliflozin 5 mg administered once daily for 26 weeks. Participants requiring rescue therapy will receive open-label metformin. Phase B: Ertugliflozin 5 mg administered once daily for 26 weeks. Participants not rescued with metformin in Phase A, will receive placebo to metformin. Participants rescued with metformin in Phase A will continue to receive metformin. Participants requiring rescue therapy during Phase B will receive open-label glimepiride.
干预措施: Metformin (Drug)
Ertugliflozin 5 mg/Ertugliflozin 5 mg
Phase A: Ertugliflozin 5 mg administered once daily for 26 weeks. Participants requiring rescue therapy will receive open-label metformin. Phase B: Ertugliflozin 5 mg administered once daily for 26 weeks. Participants not rescued with metformin in Phase A, will receive placebo to metformin. Participants rescued with metformin in Phase A will continue to receive metformin. Participants requiring rescue therapy during Phase B will receive open-label glimepiride.
干预措施: Placebo to Metformin (Drug)
Ertugliflozin 5 mg/Ertugliflozin 5 mg
Phase A: Ertugliflozin 5 mg administered once daily for 26 weeks. Participants requiring rescue therapy will receive open-label metformin. Phase B: Ertugliflozin 5 mg administered once daily for 26 weeks. Participants not rescued with metformin in Phase A, will receive placebo to metformin. Participants rescued with metformin in Phase A will continue to receive metformin. Participants requiring rescue therapy during Phase B will receive open-label glimepiride.
干预措施: Glimepiride (Drug)
Ertugliflozin 15 mg/Ertugliflozin 15 mg
Phase A: Ertugliflozin 15 mg administered once daily for 26 weeks. Participants requiring rescue therapy will receive open-label metformin. Phase B: Ertugliflozin 15 mg administered once daily for 26 weeks. Participants not rescued with metformin in Phase A, will receive placebo to metformin. Participants rescued with metformin in Phase A will continue to receive metformin. Participants requiring rescue therapy during Phase B will receive open-label glimepiride.
干预措施: Ertugliflozin 5 mg (Drug)
Ertugliflozin 15 mg/Ertugliflozin 15 mg
Phase A: Ertugliflozin 15 mg administered once daily for 26 weeks. Participants requiring rescue therapy will receive open-label metformin. Phase B: Ertugliflozin 15 mg administered once daily for 26 weeks. Participants not rescued with metformin in Phase A, will receive placebo to metformin. Participants rescued with metformin in Phase A will continue to receive metformin. Participants requiring rescue therapy during Phase B will receive open-label glimepiride.
干预措施: Ertugliflozin 10 mg (Drug)
Ertugliflozin 15 mg/Ertugliflozin 15 mg
Phase A: Ertugliflozin 15 mg administered once daily for 26 weeks. Participants requiring rescue therapy will receive open-label metformin. Phase B: Ertugliflozin 15 mg administered once daily for 26 weeks. Participants not rescued with metformin in Phase A, will receive placebo to metformin. Participants rescued with metformin in Phase A will continue to receive metformin. Participants requiring rescue therapy during Phase B will receive open-label glimepiride.
干预措施: Metformin (Drug)
Ertugliflozin 15 mg/Ertugliflozin 15 mg
Phase A: Ertugliflozin 15 mg administered once daily for 26 weeks. Participants requiring rescue therapy will receive open-label metformin. Phase B: Ertugliflozin 15 mg administered once daily for 26 weeks. Participants not rescued with metformin in Phase A, will receive placebo to metformin. Participants rescued with metformin in Phase A will continue to receive metformin. Participants requiring rescue therapy during Phase B will receive open-label glimepiride.
干预措施: Placebo to Metformin (Drug)
Ertugliflozin 15 mg/Ertugliflozin 15 mg
Phase A: Ertugliflozin 15 mg administered once daily for 26 weeks. Participants requiring rescue therapy will receive open-label metformin. Phase B: Ertugliflozin 15 mg administered once daily for 26 weeks. Participants not rescued with metformin in Phase A, will receive placebo to metformin. Participants rescued with metformin in Phase A will continue to receive metformin. Participants requiring rescue therapy during Phase B will receive open-label glimepiride.
干预措施: Glimepiride (Drug)
Placebo/Metformin
Phase A: Placebo to ertugliflozin administered once daily for 26 weeks. Participants requiring rescue therapy will receive open-label metformin. Phase B: Participants not rescued with open-label metformin in Phase A will also receive blinded metformin up to twice daily for 26 weeks in addition to placebo. Participants rescued with metformin in Phase A will continue to receive open-label metformin. Participants requiring rescue therapy during Phase B will receive open-label glimepiride.
干预措施: Placebo to Ertugliflozin (Drug)
Placebo/Metformin
Phase A: Placebo to ertugliflozin administered once daily for 26 weeks. Participants requiring rescue therapy will receive open-label metformin. Phase B: Participants not rescued with open-label metformin in Phase A will also receive blinded metformin up to twice daily for 26 weeks in addition to placebo. Participants rescued with metformin in Phase A will continue to receive open-label metformin. Participants requiring rescue therapy during Phase B will receive open-label glimepiride.
干预措施: Metformin (Drug)
Placebo/Metformin
Phase A: Placebo to ertugliflozin administered once daily for 26 weeks. Participants requiring rescue therapy will receive open-label metformin. Phase B: Participants not rescued with open-label metformin in Phase A will also receive blinded metformin up to twice daily for 26 weeks in addition to placebo. Participants rescued with metformin in Phase A will continue to receive open-label metformin. Participants requiring rescue therapy during Phase B will receive open-label glimepiride.
干预措施: Glimepiride (Drug)
结局指标
主要结局
Percentage of Participants Experiencing An Adverse Event (AE)
时间窗: Up to 54 weeks (including 2 weeks following last dose)
An AE is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. Data presented include data following the initiation of rescue therapy.
Percentage of Participants Discontinuing Study Treatment Due to an AE
时间窗: Up to 52 weeks
An AE is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. Data presented include data following the initiation of rescue therapy.
Change From Baseline In A1C at Week 26
时间窗: Baseline and Week 26
A1C is measured as percent. The change from baseline is the Week 26 A1C percent minus the Week 0 A1C percent. Laboratory measurements were performed after an overnight fast ≥10 hours in duration. Data presented exclude data following the initiation of rescue therapy.
次要结局
- Change From Baseline in Body Weight at Week 26(Baseline and Week 26)
- Baseline 2-hour Post-prandial Glucose (2-hr PPG) Level(Baseline)
- Baseline Sitting Systolic Blood Pressure (SBP)(Baseline)
- Baseline Sitting Diastolic Blood Pressure (DBP)(Baseline)
- Change From Baseline in FPG at Week 26(Baseline and Week 26)
- Percentage of Participants With A1C <7% (<53 mmol/Mol) at Week 26(Week 26)
- Change From Baseline in 2-hr PPG at Week 26(Baseline and Week 26)
- Change From Baseline in SBP at Week 26(Baseline and Week 26)
- Change From Baseline in DBP at Week 26(Baseline and Week 26)