A Phase III, Multicenter, Randomized, Double-blind Study to Evaluate the Efficacy and Safety of MK-3102 Versus Placebo in Subjects With Type 2 Diabetes Mellitus With Moderate or Severe Chronic Kidney Disease or Kidney Failure on Dialysis Who Have Inadequate Glycemic Control.
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 213
- 主要终点
- Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event (Phase A: 24-week Placebo Controlled Period)
研究概览
简要总结
The purpose of this study is to evaluate the efficacy and safety of omarigliptin in participants with type 2 diabetes mellitus and moderate or severe chronic renal insufficiency or end stage renal disease on dialysis with inadequate glycemic control. The primary hypothesis of the study is that omarigliptin compared to placebo produces greater reduction in glycosylated hemoglobin (A1C) after 24 weeks.
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
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 30 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Type 2 diabetes mellitus and be at least 30 years of age
- •Moderate or severe chronic renal insufficiency or end stage renal disease on dialysis
- •Meet one of the following criteria:
- •is currently not on an antihyperglycemic agent (AHA) and has A1C >=7% and <=10% at screening
- •is currently on a single oral AHA or low-dose dual oral combination AHA and has A1C >=6.5% and <=9% at screening
- •is currently on a stable insulin regimen (>= 15 U/day) for >= 10 weeks, with no oral AHA, and has A1C >=7.5% and <=10% and FPG >130 mg/dL at screening
- •(1) Male; (2) female not of reproductive potential; or (3) female of reproductive potential who agrees to remain abstinent or use alone or in conjunction with their partner 2 methods of contraception to prevent pregnancy during the study and for 28 days after the last dose of study drug
排除标准
- •History of type 1 diabetes mellitus or a history of ketoacidosis
- •Treated with any incretin mimetic or thiazolidinedione (TZD) within 12 weeks prior to screening or with omarigliptin at any time prior to study participation
- •History of hypersensitivity to a dipeptidyl peptidase IV (DPP-4) inhibitor
- •History of intolerance or hypersensitivity to glipizide or insulin glargine or any contraindication to glipizide or insulin glargine
- •On a weight loss program and is not in the maintenance phase, or has been on a weight loss medication in the past 6 months, or has undergone bariatric surgery within 12 months prior to study participation
- •Undergone a surgical procedure within 4 weeks prior to screening or has planned major surgery during the trial
- •On or likely to require treatment for >=2 consecutive weeks or repeated courses of corticosteroids (note: inhaled, nasal or topical corticosteroids are permitted)
- •Currently being treated for hyperthyroidism or is on thyroid replacement therapy and has not been on a stable dose for at least 6 weeks
- •If on dialysis, does not regularly adhere to dialysis schedule
- •Diagnosis of congestive heart failure with New York Heart Association (NYHA) Class IV
- •Medical history of active liver disease (other than non-alcoholic hepatic steatosis), including chronic active hepatitis B or C, primary biliary cirrhosis, or symptomatic gallbladder disease
- •Human immunodeficiency virus (HIV)
- •New or worsening coronary heart disease, congestive heart failure, myocardial infarction, unstable angina, coronary artery intervention, stroke, or transient ischemic neurological disorder within the past 3 months
- •Poorly controlled hypertension
- •Severe active peripheral vascular disease
- •History of malignancy <=5 years prior to study participation, except for adequately treated basal cell or squamous cell skin cancer, or in situ cervical cancer
- •Clinically important hematological disorder (such as aplastic anemia, myeloproliferative or myelodysplastic syndromes, thrombocytopenia)
- •Positive pregnancy test
- •Pregnant or breast-feeding, or is expecting to conceive or donate eggs during the trial, including 28 days following the last dose of study drug
- •User of recreational or illicit drugs or has had a recent history of drug abuse or routinely consumes >2 alcoholic drinks per day or >14 alcoholic drinks per week, or engages in binge drinking
研究组 & 干预措施
Omarigliptin (Phase A) → Omarigliptin (Phase B)
Phase A: omarigliptin 12.5 mg or 25 mg capsule orally once a week for 24 weeks. Phase B: omarigliptin 12.5 mg or 25 mg capsule orally once a week for 30 weeks. Participants who are not on background insulin therapy or who did not receive open-label glipizide or insulin as rescue therapy during Phase A of the study (Week 1 through Week 24) will receive matching placebo to glipizide daily in a blinded manner during Phase B of the study (Week 24 through Week 54).
干预措施: Omarigliptin (Drug)
Omarigliptin (Phase A) → Omarigliptin (Phase B)
Phase A: omarigliptin 12.5 mg or 25 mg capsule orally once a week for 24 weeks. Phase B: omarigliptin 12.5 mg or 25 mg capsule orally once a week for 30 weeks. Participants who are not on background insulin therapy or who did not receive open-label glipizide or insulin as rescue therapy during Phase A of the study (Week 1 through Week 24) will receive matching placebo to glipizide daily in a blinded manner during Phase B of the study (Week 24 through Week 54).
干预措施: Glipizide (Drug)
Omarigliptin (Phase A) → Omarigliptin (Phase B)
Phase A: omarigliptin 12.5 mg or 25 mg capsule orally once a week for 24 weeks. Phase B: omarigliptin 12.5 mg or 25 mg capsule orally once a week for 30 weeks. Participants who are not on background insulin therapy or who did not receive open-label glipizide or insulin as rescue therapy during Phase A of the study (Week 1 through Week 24) will receive matching placebo to glipizide daily in a blinded manner during Phase B of the study (Week 24 through Week 54).
干预措施: Placebo to glipizide (Drug)
Omarigliptin (Phase A) → Omarigliptin (Phase B)
Phase A: omarigliptin 12.5 mg or 25 mg capsule orally once a week for 24 weeks. Phase B: omarigliptin 12.5 mg or 25 mg capsule orally once a week for 30 weeks. Participants who are not on background insulin therapy or who did not receive open-label glipizide or insulin as rescue therapy during Phase A of the study (Week 1 through Week 24) will receive matching placebo to glipizide daily in a blinded manner during Phase B of the study (Week 24 through Week 54).
干预措施: Insulin (Biological)
Placebo to omarigliptin (Phase A) → Glipizide (Phase B)
Phase A: matching placebo to omarigliptin orally once a week for 24 weeks. Phase B: matching placebo to omarigliptin orally once a week for 30 weeks. Participants who are not on background insulin therapy or who did not receive open-label glipizide or insulin as rescue therapy during Phase A of the study (Week 1 through Week 24) will receive glipizide 2.5 daily up to a maximum of 20 mg daily (based on glycemic control) in a blinded manner during Phase B of the study (Week 24 through Week 54).
干预措施: Placebo to omarigliptin (Drug)
Placebo to omarigliptin (Phase A) → Glipizide (Phase B)
Phase A: matching placebo to omarigliptin orally once a week for 24 weeks. Phase B: matching placebo to omarigliptin orally once a week for 30 weeks. Participants who are not on background insulin therapy or who did not receive open-label glipizide or insulin as rescue therapy during Phase A of the study (Week 1 through Week 24) will receive glipizide 2.5 daily up to a maximum of 20 mg daily (based on glycemic control) in a blinded manner during Phase B of the study (Week 24 through Week 54).
干预措施: Glipizide (Drug)
Placebo to omarigliptin (Phase A) → Glipizide (Phase B)
Phase A: matching placebo to omarigliptin orally once a week for 24 weeks. Phase B: matching placebo to omarigliptin orally once a week for 30 weeks. Participants who are not on background insulin therapy or who did not receive open-label glipizide or insulin as rescue therapy during Phase A of the study (Week 1 through Week 24) will receive glipizide 2.5 daily up to a maximum of 20 mg daily (based on glycemic control) in a blinded manner during Phase B of the study (Week 24 through Week 54).
干预措施: Placebo to glipizide (Drug)
Placebo to omarigliptin (Phase A) → Glipizide (Phase B)
Phase A: matching placebo to omarigliptin orally once a week for 24 weeks. Phase B: matching placebo to omarigliptin orally once a week for 30 weeks. Participants who are not on background insulin therapy or who did not receive open-label glipizide or insulin as rescue therapy during Phase A of the study (Week 1 through Week 24) will receive glipizide 2.5 daily up to a maximum of 20 mg daily (based on glycemic control) in a blinded manner during Phase B of the study (Week 24 through Week 54).
干预措施: Insulin (Biological)
结局指标
主要结局
Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event (Phase A: 24-week Placebo Controlled Period)
时间窗: Up to 24 weeks
An adverse event is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. Presented data exclude data after glycemic rescue.
Percentage of Participants Who Experienced at Least One Adverse Event (Phase A: 24-week Placebo Controlled Period + Phase B: 30-week Active Controlled Period)
时间窗: Up to 58 weeks (including 28 days following the last dose of study therapy)
An adverse event is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. Presented data exclude data after glycemic rescue.
Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event (Phase A: 24-week Placebo Controlled Period + Phase B: 30-week Active Controlled Period)
时间窗: Up to 54 weeks
An adverse event is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. Presented data exclude data after glycemic rescue.
Change From Baseline in Glycosylated Hemoglobin (A1C) at Week 24
时间窗: Baseline and Week 24
A1C is measured as a percent. Change from baseline in A1C at Week 24 was analyzed using constrained longitudinal data analysis (cLDA) method with a restriction of the same baseline mean across treatment groups. The cLDA model included terms for treatment, renal insufficiency stratum, baseline treatment with insulin stratum, time, the interaction of time by treatment, the interaction of time by renal insufficiency stratum, and the interaction of time by baseline treatment with insulin stratum.
Percentage of Participants Who Experienced at Least One Adverse Event (Phase A: 24-week Placebo Controlled Period)
时间窗: Up to 28 weeks (including 28 days following the last dose of study therapy for participants who discontinued study drug)
An adverse event is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. Presented data exclude data after glycemic rescue.
次要结局
- Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24(Baseline and Week 24)
- Change From Baseline in A1C at Week 54(Baseline and Week 54)
- Change From Baseline in FPG at Week 54(Baseline and Week 54)
- Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 24(Baseline and Week 24)
- Change From Baseline in eGFR at Week 54(Baseline and Week 54)