A Phase IV, Multicenter, Randomized, Placebo-Controlled, Parallel-Group, Double-Blind Trial and Subsequent Open-Label, Extension Trial to Assess the Safety and Efficacy of Addition of Omarigliptin in Japanese Patients With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control on Insulin Monotherapy in Addition to Diet and Exercise Therapy
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 184
- 主要终点
- Percentage of Participants Who Experienced One or More Adverse Events (AE) Excluding Data After Glycemic Rescue (Phase A)
研究概览
简要总结
This study will examine the efficacy of omarigliptin 25 mg once weekly compared to placebo in Japanese patients with T2DM who have inadequate glycemic control on insulin monotherapy in addition to diet and exercise therapy. The primary hypothesis of the study is that omarigliptin 25 mg once weekly provides greater reduction in hemoglobin A1C (HbA1c) compared with placebo as assessed by change from baseline to Week 16 [Phase A (double-blind period)].
详细描述
After a screening period of up to 2 weeks followed by a pretreatment period of 2 or 10 weeks, each participant will be receiving assigned double-blind treatment (omarigliptin 25 mg or placebo once weekly) for approximately 16 weeks (Phase A) followed by 36 weeks of open-label treatment (omarigliptin 25 mg once weekly, Phase B). After the end of treatment each participant will be followed for 21 days.
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
- 20 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Have T2DM
- •Meet all of following criteria at Week -2 of pre-randomization
- •On diet and exercise therapy for 6 weeks or longer, AND
- •Have been on a stable dosage and administration of insulin (8 to 40 units/day) for 10 weeks or longer, AND.
- •Have not been on any additional anti-hyperglycemic agent (AHAs, except for insulin monotherapy) for 8 weeks or longer, AND
- •HbA1c ≥7.5% and ≤10.0%
- •Fasting Plasma Glucose (FPG) ≥126 mg/dL and ≤230 mg/dL
- •Have a body mass index (BMI) >18 kg/m^2 and <40 kg/m^2
- •A male or female not of reproductive potential or a female of reproductive potential and agrees to remain abstinent from heterosexual activity, or agrees to use acceptable contraception to prevent pregnancy.
排除标准
- •Has type 1 diabetes mellitus or has a history of diabetic ketoacidosis.
- •Has a history of being administered any of the following AHAs including fixed dose combination (FDC) containing the following ingredients:
- •Thiazolidinediones within 12 weeks
- •Glucagon-like peptide 1 (GLP-1) receptor agonists within 12 weeks
- •Omarigliptin at any time
- •Has history of severe hypoglycemia with coma or loss of consciousness, or for whom hypoglycemia was observed greater or equal to two times per week within 8 weeks
- •Is currently participating in or has participated in another study with an investigational compound or device within the prior 12 weeks
- •Has undergone a surgical procedure within 8 weeks or has planned major surgery during the study.
- •Receives a lipid-lowering medication or thyroid replacement therapy at unstable dosage and administration
- •Has poorly controlled hypertension
- •Has a medical history of active liver disease, including chronic active hepatitis B or C, primary biliary cirrhosis, or symptomatic gallbladder disease.
- •Has human immunodeficiency virus (HIV).
- •Has had new or worsening signs or symptoms of coronary heart disease or congestive heart failure within the past 3 months, or has acute coronary syndrome, coronary artery intervention, or stroke or transient ischemic neurological disorder within the past 3 months
- •Has severe peripheral vascular disease.
- •Has a history of malignancy ≤ 5 years, except for adequately treated basal cell or squamous cell skin cancer, or in situ cervical cancer:
- •Has a clinically important hematological disorder.
- •(For women of childbearing potential) has a positive urine pregnancy test.
- •Is pregnant or breast feeding
- •Is expected to conceive during the study
- •Is expected to undergo hormonal therapy in preparation to donate eggs during the study
- •Routinely consumes >14 alcoholic drinks per week or engages in binge drinking
- •Has donated or plans to donate blood products of >300 mL within 8 weeks or during the study
- •Has received or plans to receive blood products within 12 weeks or during the study
研究组 & 干预措施
Omarigliptin 25 mg
Omarigliptin 25 mg once weekly for 52 weeks (Phase A and B)
干预措施: Omarigliptin (Drug)
Omarigliptin 25 mg
Omarigliptin 25 mg once weekly for 52 weeks (Phase A and B)
干预措施: Insulin (Biological)
Placebo→Omarigliptin 25 mg
Placebo to Omarigliptin once weekly for 16 weeks (Phase A) switching to Omarigliptin 25 mg once weekly for 36 weeks (Phase B)
干预措施: Omarigliptin (Drug)
Placebo→Omarigliptin 25 mg
Placebo to Omarigliptin once weekly for 16 weeks (Phase A) switching to Omarigliptin 25 mg once weekly for 36 weeks (Phase B)
干预措施: Placebo (Drug)
Placebo→Omarigliptin 25 mg
Placebo to Omarigliptin once weekly for 16 weeks (Phase A) switching to Omarigliptin 25 mg once weekly for 36 weeks (Phase B)
干预措施: Insulin (Biological)
结局指标
主要结局
Percentage of Participants Who Experienced One or More Adverse Events (AE) Excluding Data After Glycemic Rescue (Phase A)
时间窗: Up to Week 16
An adverse event is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an adverse event. Participants that met rescue criteria had their insulin dose adjusted as determined clinically appropriate by the investigator to manage glycemic control. Data after glycemic rescue were excluded from this analysis.
Percentage of Participants Who Discontinued Study Drug Due to an AE Excluding Data After Glycemic Rescue (Phase A)
时间窗: Up to Week 16
An adverse event is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an adverse event. Participants that met rescue criteria had their insulin dose adjusted as determined clinically appropriate by the investigator to manage glycemic control. Data after glycemic rescue were excluded from this analysis.
Constrained Longitudinal Data Analysis of Change From Baseline in Hemoglobin A1c (HbA1c) at Week 16 Excluding Data After Glycemic Rescue (Phase A)
时间窗: Baseline (Day 1) and Week 16
HbA1c is a measure of the percentage of glycated hemoglobin in the blood. Participant whole blood samples were collected at baseline and Week 16 to determine the Constrained Longitudinal Data Analysis least squares mean HbA1c change from baseline (i.e., HbA1c at Week 16 minus HbA1c at baseline). Participants that met rescue criteria had their insulin dose adjusted as determined clinically appropriate by the investigator to manage glycemic control. Data after glycemic rescue were excluded from this analysis. Negative data values indicated a reduction in HbA1c levels.
Percentage of Participants Who Experienced One or More AE (Omarigliptin [Phase A+B]; Placebo→Omarigliptin [Phase B Only])
时间窗: Up to Week 52
An adverse event is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an adverse event. Participants that met rescue criteria had their insulin dose adjusted as determined clinically appropriate by the investigator to manage glycemic control. The results for the Placebo→Omarigliptin group summarized data from the open label period only (36 weeks), which corresponds to the study interval in which those participants were exposed to omarigliptin.
Percentage of Participants Who Discontinued Study Drug Due to an AE Including Data After Glycemic Rescue (Omarigliptin [Phase A+B]; Placebo→Omarigliptin [Phase B Only])
时间窗: Up to Week 52
An adverse event is defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an adverse event. Participants that met rescue criteria had their insulin dose adjusted as determined clinically appropriate by the investigator to manage glycemic control. The results for the Placebo→Omarigliptin group summarized data from the open label period only (36 weeks), which corresponds to the study interval in which those participants were exposed to omarigliptin.
次要结局
- Percentage of Participants Achieving Hemoglobin A1c Goals (<6.5%) at Week 52 (Phase A+B)(Week 52)
- Percentage of Participants Achieving HbA1c Goals (<6.5%) at Week 16 Constrained Longitudinal Data Analysis Using Multiple Imputation Excluding Data After Glycemic Rescue (Phase A)(Week 16)
- Percentage of Participants Achieving Hemoglobin A1c Goals (<7.0%) at Week 52 (Phase A+B)(Week 52)
- Percentage of Participants Achieving Hemoglobin A1c Goals (<7.0%) at Week 16 Constrained Longitudinal Data Analysis Using Multiple Imputation Excluding Data After Glycemic Rescue (Phase A)(Week 16)
- Constrained Longitudinal Data Analysis of Change From Baseline in 1,5-anhydroglucitol (1,5-AG) at Week 16 Excluding Data After Glycemic Rescue (Phase A)(Baseline (Day 1) and Week 16)
- Constrained Longitudinal Data Analysis of Change From Baseline in Fasting Plasma Glucose (FPG) at Week 16 Excluding Data After Glycemic Rescue (Phase A)(Baseline (Day 1) and Week 16)
- Change From Baseline in Hemoglobin A1c (HbA1c) at Week 52 (Phase A+B)(Baseline (Day 1) and Week 52)
- Change From Baseline in Fasting Plasma Glucose (FPG) at Week 52 (Phase A+B)(Baseline (Day 1) and Week 52)