A Phase III, Randomized, Double-blind, Clinical Trial to Study the Efficacy and Safety of MK-0431D (a Fixed-dose Combination [FDC] of Sitagliptin and Simvastatin) for the Treatment of Patients With Type 2 Diabetes Mellitus (T2DM) With Inadequate Glycemic Control on Metformin Monotherapy
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 299
- 主要终点
- Change From Baseline in Hemoglobin A1C (A1C) at Week 16 (Sitagliptin/Simvastatin FDC vs. Sitagliptin)
研究概览
简要总结
The purpose of this study is to assess the efficacy and safety of sitagliptin/simvastatin fixed-dose combination (FDC) in participants with T2DM who have inadequate glycemic control while on metformin monotherapy. The primary hypothesis of this study is that after 16 weeks of therapy, the mean change from baseline in hemoglobin A1C (A1C) in participants treated with sitagliptin/simvastatin FDC is non-inferior compared to sitagliptin alone.
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 79 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •(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 14 days after the last dose of study drug
- •is currently on metformin monotherapy at a daily dose of at least 1500 mg for at least 10 weeks
- •is not on a lipid-lowering agent for at least 6 weeks prior to entering the study
排除标准
- •has history of type 1 diabetes mellitus (T1DM), or a history of ketoacidosis or possibly has T1DM
- •has been on a thiazolidinedione (TZD) within the previous 16 weeks
- •has been treated with a statin or other lipid-lowering agent (including over-the-counter [OTC] supplements) within the previous 6 weeks
- •currently participating in or has participated in another clinical study within the past 12 weeks
- •intends to consume >1.2 liters of grapefruit juice daily during the study
- •is on or likely to require treatment for at least 2 consecutive weeks or repeated courses of corticosteroids (inhaled, nasal and topical corticosteroids are permitted)
- •intolerance or hypersensitivity to sitagliptin, simvastatin, metformin or glimepiride
- •is on a weight loss program and not in the maintenance phase or has started a weight loss medication or has undergone bariatric surgery in the previous 12 months
- •has undergone a surgical procedure in the past 4 weeks or planned major surgery during the study
- •has symptomatic hyperglycemia that requires immediate initiation, adjustment, or addition of antihyperglycemic therapy
- •has a history of myopathy or rhabdomyolysis with any statin
- •has cardiovascular disease, a diagnosis of congestive heart failure, or uncontrolled high blood pressure
- •has a history of active liver disease
- •has chronic progressive neuromuscular disorder, human immunodeficiency virus (HIV), hematological disorder, or uncontrolled endocrine or metabolic disease
- •is currently being treated for hyperthyroidism or is on thyroid hormone therapy and has not been on a stable dose for at least 6 weeks
- •has a history of malignancy in the previous 5 years (excluding adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer)
- •is pregnant or breast feeding, or is expecting to conceive or donate eggs during the course of the study, including 14 days after the last dose of study drug
- •is a user of recreational or illicit drugs or has had a recent history of drug abuse
- •consumes >2 alcoholic drinks per day or >14 alcoholic drinks per week, or engages in binge drinking
研究组 & 干预措施
Sitagliptin/Simvastatin FDC
Sitagliptin 100 mg/simvastatin 40 mg FDC plus placebo to sitagliptin plus placebo to simvastatin administered orally once daily in the evening for 16 weeks. Participants will continue on their stable pre-screening metformin dose and dosing regimen of >=1500 mg daily for the duration of the study. Participants may receive glimepiride 1 mg once daily or 2 mg once daily (may be up-titrated to 6 mg once daily) as rescue therapy.
干预措施: Sitagliptin/Simvastatin FDC (Drug)
Sitagliptin/Simvastatin FDC
Sitagliptin 100 mg/simvastatin 40 mg FDC plus placebo to sitagliptin plus placebo to simvastatin administered orally once daily in the evening for 16 weeks. Participants will continue on their stable pre-screening metformin dose and dosing regimen of >=1500 mg daily for the duration of the study. Participants may receive glimepiride 1 mg once daily or 2 mg once daily (may be up-titrated to 6 mg once daily) as rescue therapy.
干预措施: Placebo to sitagliptin (Drug)
Sitagliptin/Simvastatin FDC
Sitagliptin 100 mg/simvastatin 40 mg FDC plus placebo to sitagliptin plus placebo to simvastatin administered orally once daily in the evening for 16 weeks. Participants will continue on their stable pre-screening metformin dose and dosing regimen of >=1500 mg daily for the duration of the study. Participants may receive glimepiride 1 mg once daily or 2 mg once daily (may be up-titrated to 6 mg once daily) as rescue therapy.
干预措施: Placebo to simvastatin (Drug)
Sitagliptin/Simvastatin FDC
Sitagliptin 100 mg/simvastatin 40 mg FDC plus placebo to sitagliptin plus placebo to simvastatin administered orally once daily in the evening for 16 weeks. Participants will continue on their stable pre-screening metformin dose and dosing regimen of >=1500 mg daily for the duration of the study. Participants may receive glimepiride 1 mg once daily or 2 mg once daily (may be up-titrated to 6 mg once daily) as rescue therapy.
干预措施: Metformin (Drug)
Sitagliptin/Simvastatin FDC
Sitagliptin 100 mg/simvastatin 40 mg FDC plus placebo to sitagliptin plus placebo to simvastatin administered orally once daily in the evening for 16 weeks. Participants will continue on their stable pre-screening metformin dose and dosing regimen of >=1500 mg daily for the duration of the study. Participants may receive glimepiride 1 mg once daily or 2 mg once daily (may be up-titrated to 6 mg once daily) as rescue therapy.
干预措施: Glimepiride (Drug)
Sitagliptin
Sitagliptin 100 mg plus placebo to simvastatin plus placebo to sitagliptin/simvastatin FDC administered orally once daily in the evening for 16 weeks. Participants will continue on their stable pre-screening metformin dose and dosing regimen of >=1500 mg daily for the duration of the study. Participants may receive glimepiride 1 mg once daily or 2 mg once daily (may be up-titrated to 6 mg once daily) as rescue therapy.
干预措施: Sitagliptin (Drug)
Sitagliptin
Sitagliptin 100 mg plus placebo to simvastatin plus placebo to sitagliptin/simvastatin FDC administered orally once daily in the evening for 16 weeks. Participants will continue on their stable pre-screening metformin dose and dosing regimen of >=1500 mg daily for the duration of the study. Participants may receive glimepiride 1 mg once daily or 2 mg once daily (may be up-titrated to 6 mg once daily) as rescue therapy.
干预措施: Placebo to simvastatin (Drug)
Sitagliptin
Sitagliptin 100 mg plus placebo to simvastatin plus placebo to sitagliptin/simvastatin FDC administered orally once daily in the evening for 16 weeks. Participants will continue on their stable pre-screening metformin dose and dosing regimen of >=1500 mg daily for the duration of the study. Participants may receive glimepiride 1 mg once daily or 2 mg once daily (may be up-titrated to 6 mg once daily) as rescue therapy.
干预措施: Placebo to Sitagliptin/Simvastatin FDC (Drug)
Sitagliptin
Sitagliptin 100 mg plus placebo to simvastatin plus placebo to sitagliptin/simvastatin FDC administered orally once daily in the evening for 16 weeks. Participants will continue on their stable pre-screening metformin dose and dosing regimen of >=1500 mg daily for the duration of the study. Participants may receive glimepiride 1 mg once daily or 2 mg once daily (may be up-titrated to 6 mg once daily) as rescue therapy.
干预措施: Metformin (Drug)
Sitagliptin
Sitagliptin 100 mg plus placebo to simvastatin plus placebo to sitagliptin/simvastatin FDC administered orally once daily in the evening for 16 weeks. Participants will continue on their stable pre-screening metformin dose and dosing regimen of >=1500 mg daily for the duration of the study. Participants may receive glimepiride 1 mg once daily or 2 mg once daily (may be up-titrated to 6 mg once daily) as rescue therapy.
干预措施: Glimepiride (Drug)
Simvastatin
Simvastatin 40 mg plus placebo to sitagliptin plus placebo to sitagliptin/simvastatin FDC administered orally once daily in the evening for 16 weeks. Participants will continue on their stable pre-screening metformin dose and dosing regimen of >=1500 mg daily for the duration of the study. Participants may receive glimepiride 1 mg once daily or 2 mg once daily (may be up-titrated to 6 mg once daily) as rescue therapy.
干预措施: Simvastatin (Drug)
Simvastatin
Simvastatin 40 mg plus placebo to sitagliptin plus placebo to sitagliptin/simvastatin FDC administered orally once daily in the evening for 16 weeks. Participants will continue on their stable pre-screening metformin dose and dosing regimen of >=1500 mg daily for the duration of the study. Participants may receive glimepiride 1 mg once daily or 2 mg once daily (may be up-titrated to 6 mg once daily) as rescue therapy.
干预措施: Placebo to sitagliptin (Drug)
Simvastatin
Simvastatin 40 mg plus placebo to sitagliptin plus placebo to sitagliptin/simvastatin FDC administered orally once daily in the evening for 16 weeks. Participants will continue on their stable pre-screening metformin dose and dosing regimen of >=1500 mg daily for the duration of the study. Participants may receive glimepiride 1 mg once daily or 2 mg once daily (may be up-titrated to 6 mg once daily) as rescue therapy.
干预措施: Placebo to Sitagliptin/Simvastatin FDC (Drug)
Simvastatin
Simvastatin 40 mg plus placebo to sitagliptin plus placebo to sitagliptin/simvastatin FDC administered orally once daily in the evening for 16 weeks. Participants will continue on their stable pre-screening metformin dose and dosing regimen of >=1500 mg daily for the duration of the study. Participants may receive glimepiride 1 mg once daily or 2 mg once daily (may be up-titrated to 6 mg once daily) as rescue therapy.
干预措施: Metformin (Drug)
Simvastatin
Simvastatin 40 mg plus placebo to sitagliptin plus placebo to sitagliptin/simvastatin FDC administered orally once daily in the evening for 16 weeks. Participants will continue on their stable pre-screening metformin dose and dosing regimen of >=1500 mg daily for the duration of the study. Participants may receive glimepiride 1 mg once daily or 2 mg once daily (may be up-titrated to 6 mg once daily) as rescue therapy.
干预措施: Glimepiride (Drug)
结局指标
主要结局
Change From Baseline in Hemoglobin A1C (A1C) at Week 16 (Sitagliptin/Simvastatin FDC vs. Sitagliptin)
时间窗: Baseline and Week 16
A1C is measured as percent. Thus, this change from baseline reflects the Week 16 A1C percent minus the Week 0 A1C percent. This primary outcome measure only includes results for sitagliptin/simvastatin FDC vs. sitagliptin. Results for simvastatin are presented below under secondary outcome measures.
Number of Participants Who Experienced at Least One Adverse Event (AE)
时间窗: Up to 16 weeks for non-serious AEs, up to 18 weeks for serious AEs
Excludes data after rescue therapy. Adverse event is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the Sponsor's product, whether or not considered related to the use of the product.
Number of Participants Who Discontinued Study Drug Due to an Adverse Event
时间窗: Up to 16 weeks
Excludes data after rescue therapy. Adverse event is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the Sponsor's product, whether or not considered related to the use of the product.
次要结局
- Change From Baseline in A1C at Week 16 (Sitagliptin/Simvastatin FDC vs. Simvastatin)(Baseline and Week 16)
- Change From Baseline in Fasting Plasma Glucose (FPG) at Week 16(Baseline and Week 16)
- Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at Week 16(Baseline and Week 16)
- Percent Change From Baseline in Total Cholesterol (TC) at Week 16(Baseline and Week 16)
- Percent Change From Baseline in Apolipoprotein B (Apo B) at Week 16(Baseline and Week 16)
- Percent Change From Baseline in Non-high Density Lipoprotein Cholesterol (Non-HDL-C) at Week 16(Baseline and Week 16)
- Percent Change From Baseline in Triglycerides (TG) at Week 16(Baseline and Week 16)
- Percent Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) at Week 16(Baseline and Week 16)
- Percent Change From Baseline in Very Low-density Lipoprotein Cholesterol (VLDL-C) at Week 16(Baseline and Week 16)
- Percentage of Participants With A1C Level <7% at Week 16(Week 16)