A Phase III, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Clinical Trial to Evaluate the Safety and Efficacy of Ertugliflozin (MK-8835/PF-04971729) in the Treatment of Subjects With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control on Metformin and Sitagliptin
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 464
- 主要终点
- Change From Baseline in Hemoglobin A1C at Week 26
研究概览
简要总结
This is a safety and efficacy study of ertugliflozin (MK-8835/PF-04971729) in the treatment of participants with type 2 diabetes mellitus who have inadequate glycemic control on metformin and sitagliptin. The primary objective of the trial is to assess the hemoglobin A1C (A1C)-lowering efficacy of the addition of ertugliflozin compared to the addition of placebo with an underlying hypothesis that addition of treatment with ertugliflozin provides greater reduction in A1C compared with the addition of placebo; the primary objective will be tested for both 5-mg and 15-mg doses of ertugliflozin.
详细描述
The duration of the trial will be approximately 69 weeks. This will include a 1-week Screening Period, an up to 12-week wash-off/titration /dose-stabilization period, a 2-week single-blind, placebo run-in period, a 52-week double-blind, placebo-controlled treatment period (including a 26-week Phase A and 26-week Phase B), and a post-treatment telephone contact 14 days after the last dose of blinded investigational product.
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 type 2 diabetes mellitus (T2DM)
- •On stable diabetes therapy of metformin with either sitagliptin or another dipeptidyl peptidase-4 (DPP-4) inhibitor or a sulfonylurea (SU) prior to study participation and is willing to wash-off/switch from another DPP-4 inhibitor/SU to sitagliptin
- •Body Mass Index (BMI) greater than or equal to 18.0 kg/m^2
- •Male, postmenopausal female or surgically sterile female
- •If a female of reproductive potential, agrees to remain abstinent or to use (or have their partner use) 2 acceptable combinations of birth control while participating in the trial and for 14 days after the last use of study drug
排除标准
- •History of type 1 diabetes mellitus or a history of ketoacidosis
- •History of other specific types of diabetes (e.g., genetic syndromes, secondary pancreatic diabetes, diabetes due to endocrine disorders, drug- or chemical-induced, and post-organ transplant)
- •A known hypersensitivity or intolerance to any sodium-glucose co-transporter 2 (SGLT2) or DPP-4 inhibitor
- •On a weight-loss program or weight-loss medication or other medication associated with weight changes and is not weight stable
- •Has undergone bariatric surgery within the past 12 months or >12 months and is not weight stable
- •Has been treated with insulin (except for short-term use [<= 7 days]), injectable antihyperglycemic agents (AHAs) (e.g., pramlintide, exenatide, liraglutide), pioglitazone or rosiglitazone, other sodium-glucose co-transporter 2 (SGLT2) inhibitors, alpha glucosidase inhibitors or meglitinides, bromocriptine (Cycloset™), colesevelam (Welchol™), or any other non-protocol approved AHAs within 12 weeks of study participation
- •Has active, obstructive uropathy or indwelling urinary catheter
- •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 history of malignancy ≤5 years prior to study participation, except for adequately treated basal or squamous cell skin cancer or in situ cervical cancer
- •Known history of Human Immunodeficiency Virus (HIV)
- •Has blood dyscrasias or any disorders causing hemolysis or unstable red blood cells or any other clinically significant hematological disorder (such as aplastic anemia, myeloproliferative or myelodysplastic syndromes, thrombocytopenia)
- •A medical history of active liver disease (other than nonalcoholic hepatic steatosis), including chronic active hepatitis B or C, primary biliary cirrhosis, or active symptomatic gallbladder disease
- •Has any clinically significant malabsorption condition
- •If taking thyroid replacement therapy, has not been on a stable dose for at least 6 weeks prior to study participation
- •Has been previously randomized in a study with ertugliflozin
- •Has participated in other studies involving an investigational drug within 30 days prior or during study participation
- •Has undergone a surgical procedure within 6 weeks prior to or planned major surgery during study participation
- •Has a positive urine pregnancy test
- •Is pregnant or breast-feeding, or is planning to conceive during the trial, including 14 days following the last dose of study medication
- •Planning to undergo hormonal therapy in preparation to donate eggs during the trial, including 14 days following the last dose of study medication
- •Excessive consumption of alcoholic beverages or binge drinking
- •Has donated blood or blood products within 6 weeks of study participation or plans to donate blood or blood products at any time during the trial
研究组 & 干预措施
Ertugliflozin 5 mg
Ertugliflozin, 5 mg, oral, once daily for 52 weeks
干预措施: Ertugliflozin 5 mg (Drug)
Ertugliflozin 5 mg
Ertugliflozin, 5 mg, oral, once daily for 52 weeks
干预措施: Metformin (Drug)
Ertugliflozin 5 mg
Ertugliflozin, 5 mg, oral, once daily for 52 weeks
干预措施: Sitagliptin (Drug)
Ertugliflozin 5 mg
Ertugliflozin, 5 mg, oral, once daily for 52 weeks
干预措施: Glimepiride (Drug)
Ertugliflozin 5 mg
Ertugliflozin, 5 mg, oral, once daily for 52 weeks
干预措施: Insulin (Biological)
Ertugliflozin 5 mg
Ertugliflozin, 5 mg, oral, once daily for 52 weeks
干预措施: Placebo for ertugliflozin 10 mg (Drug)
Ertugliflozin 15 mg
Ertugliflozin, 15 mg, oral, once daily for 52 weeks
干预措施: Ertugliflozin 15 mg (Drug)
Ertugliflozin 15 mg
Ertugliflozin, 15 mg, oral, once daily for 52 weeks
干预措施: Metformin (Drug)
Ertugliflozin 15 mg
Ertugliflozin, 15 mg, oral, once daily for 52 weeks
干预措施: Sitagliptin (Drug)
Ertugliflozin 15 mg
Ertugliflozin, 15 mg, oral, once daily for 52 weeks
干预措施: Glimepiride (Drug)
Ertugliflozin 15 mg
Ertugliflozin, 15 mg, oral, once daily for 52 weeks
干预措施: Insulin (Biological)
Placebo
Matching placebo to ertuglifozin, oral, once daily for 52 weeks
干预措施: Placebo for ertugliflozin 5 mg (Drug)
Placebo
Matching placebo to ertuglifozin, oral, once daily for 52 weeks
干预措施: Metformin (Drug)
Placebo
Matching placebo to ertuglifozin, oral, once daily for 52 weeks
干预措施: Sitagliptin (Drug)
Placebo
Matching placebo to ertuglifozin, oral, once daily for 52 weeks
干预措施: Glimepiride (Drug)
Placebo
Matching placebo to ertuglifozin, oral, once daily for 52 weeks
干预措施: Insulin (Biological)
Placebo
Matching placebo to ertuglifozin, oral, once daily for 52 weeks
干预措施: Placebo for ertugliflozin 10 mg (Drug)
结局指标
主要结局
Change From Baseline in Hemoglobin A1C at Week 26
时间窗: Baseline and Week 26
A1C is measured as percent. Thus this change from baseline reflects 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.
Percentage of Participants Experiencing An Adverse Event (AE)
时间窗: Up to Week 54
An adverse event is defined as any untoward medical occurrence in a participant 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 Week 52
An adverse event is defined as any untoward medical occurrence in a participant 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.
次要结局
- Change From Baseline in Fasting Plasma Glucose (FPG) at Week 26(Baseline and Week 26)
- Change From Baseline in Body Weight at Week 26(Baseline and Week 26)
- Percentage of Participants With an A1C <7% (53 mmol/Mol) at Week 26(Week 26)
- Change From Baseline in Sitting Systolic Blood Pressure at Week 26(Baseline and Week 26)
- Change From Baseline in Hemoglobin A1C at Week 52(Baseline and Week 52)
- Change From Baseline in FPG at Week 52(Baseline and Week 52)
- Change From Baseline in Sitting Systolic Blood Pressure at Week 52(Baseline and Week 52)
- Change From Baseline in Sitting Diastolic Blood Pressure at Week 26(Baseline and Week 26)
- Change From Baseline in Sitting Diastolic Blood Pressure at Week 52(Baseline and Week 52)
- Percentage of Participants Receiving Glycemic Rescue Medication by Week 26(Week 26)
- Change From Baseline in Body Weight at Week 52(Baseline and Week 52)
- Percentage of Participants With an A1C <7% (53 mmol/Mol) at Week 52(Week 52)
- Percentage of Participants Receiving Glycemic Rescue Medication by Week 52(Week 52)
- Time to Initiation of Glycemic Rescue by Week 26(Up to Week 26 (plus 30 days for 1 placebo participant))
- Time to Initiation of Glycemic Rescue by Week 52(Up to week 52)
- Baseline Homeostasis Model Assessment of β-cell Function (HOMA-%β) Value(Baseline)
- Change From Baseline in HOMA-%β at Week 26(Baseline and Week 26)
- Change From Baseline in HOMA-%β at Week 52(Baseline and Week 52)
- Baseline EQ-5D 3-level Version (EQ-5D-3L) Questionnaire Score(Baseline)
- Change From Baseline in EQ-5D-3L Questionnaire Score at Week 26(Baseline and Week 26)
- Change From Baseline in EQ-5D-3L Score at Week 52(Baseline and Week 52)