A Phase III Randomized Clinical Trial to Study the Efficacy and Safety of the Co-administration of Sitagliptin and Atorvastatin in Patients With Type 2 Diabetes Mellitus With Inadequate Glycemic Control on Metformin Monotherapy
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 166
- 主要终点
- Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 16
研究概览
简要总结
This two-phase study was to examine if 16 weeks of treatment with sitagliptin in combination with atorvastatin reduces hemoglobin A1C (A1C) and low density lipoprotein cholesterol (LDL-C) from baseline more than atorvastatin alone and sitagliptin alone, respectively. Following a single-blind placebo run-in period, participants were to be randomized to one of three treatment arms (sitagliptin monotherapy, atorvastatin monotherapy, or sitagliptin plus atorvastatin) for 16 weeks (Phase A). During Phase B of the study (Weeks 16 through 54), participants were to receive either sitagliptin plus atorvastatin or glimepiride plus atorvastatin. The primary hypotheses were that after 16 weeks of treatment, sitagliptin in combination with atorvastatin reduces A1C from baseline more than atorvastatin alone, and that atorvastatin in combination with sitagliptin lowers LDL-C from baseline more than 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
- •has type 2 diabetes mellitus
- •is a male, or a female who is highly unlikely to conceive
- •is currently on monotherapy with metformin (at least 1500 mg/day) for at least 8 weeks
- •is not on statin therapy or other lipid-lowering agents for at least 6 weeks
排除标准
- •has a history of type 1 diabetes mellitus, ketoacidosis or possibly has type 1 diabetes
- •has ever taken a dipeptidyl peptidase IV inhibitor (such as sitagliptin, vildagliptin, alogliptin, or saxagliptin) or a glucagon-like peptide-1 mimetic (such as exenatide or liraglutide), or has required insulin therapy within 12 weeks prior to signing informed consent
- •has been on a peroxisome proliferator-activated receptor gamma agonist within the prior 12 weeks
- •has been treated with a statin or other lipid-lowering agents, including over the counter supplements of fish oils within 6 weeks
- •intends to consume at least 1.2 liters of grapefruit juice per day during the course of the study
- •is on or is likely to require treatment with 14 consecutive days or more, or repeated courses of corticosteroids
- •is on a weight loss program and not in the maintenance phase or has started a weight loss medication (such as orlistat or sibutramine) within the prior 8 weeks
- •has undergone a surgical procedure within the prior 4 weeks
- •has a history of myopathy or rhabdomyolysis with any statin.
- •has cardiovascular disease
- •has New York Heart Association (NYHA) Class III or IV congestive heart failure, inadequately controlled hypertension, a medical history of active liver disease, chronic progressive neuromuscular disorder, is human immunodeficiency virus (HIV) positive, has a clinically significant hematological disorder, uncontrolled endocrine or metabolic disease known to influence glycemic control or serum lipids/lipoproteins, untreated hyperthyroidism or is currently under treatment for hyperthyroidism
- •has a history of malignancy within 5 years, except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer
- •is pregnant or breastfeeding, or is intending to become pregnant or donate eggs within the projected duration of the study and post-study follow-up period
- •uses recreational or illicit drugs or has had a recent history (within the last year) of drug abuse or increased alcohol consumption
研究组 & 干预措施
Sitagliptin/Sitagliptin + Atorvastatin
In Phase A, participants received sitagliptin 100 mg plus matching placebo to atorvastatin daily for 16 weeks. Participants continuing to Phase B received sitagliptin 100 mg plus atorvastatin 80 mg plus matching placebo to glimepiride daily for an additional 38 weeks.
干预措施: Sitagliptin (Drug)
Sitagliptin/Sitagliptin + Atorvastatin
In Phase A, participants received sitagliptin 100 mg plus matching placebo to atorvastatin daily for 16 weeks. Participants continuing to Phase B received sitagliptin 100 mg plus atorvastatin 80 mg plus matching placebo to glimepiride daily for an additional 38 weeks.
干预措施: Atorvastatin (Drug)
Sitagliptin/Sitagliptin + Atorvastatin
In Phase A, participants received sitagliptin 100 mg plus matching placebo to atorvastatin daily for 16 weeks. Participants continuing to Phase B received sitagliptin 100 mg plus atorvastatin 80 mg plus matching placebo to glimepiride daily for an additional 38 weeks.
干预措施: Placebo to atorvastatin (Other)
Sitagliptin/Sitagliptin + Atorvastatin
In Phase A, participants received sitagliptin 100 mg plus matching placebo to atorvastatin daily for 16 weeks. Participants continuing to Phase B received sitagliptin 100 mg plus atorvastatin 80 mg plus matching placebo to glimepiride daily for an additional 38 weeks.
干预措施: Metformin (open-label) (Drug)
Sitagliptin/Sitagliptin + Atorvastatin
In Phase A, participants received sitagliptin 100 mg plus matching placebo to atorvastatin daily for 16 weeks. Participants continuing to Phase B received sitagliptin 100 mg plus atorvastatin 80 mg plus matching placebo to glimepiride daily for an additional 38 weeks.
干预措施: Glimepiride (open-label) (Drug)
Sitagliptin/Sitagliptin + Atorvastatin
In Phase A, participants received sitagliptin 100 mg plus matching placebo to atorvastatin daily for 16 weeks. Participants continuing to Phase B received sitagliptin 100 mg plus atorvastatin 80 mg plus matching placebo to glimepiride daily for an additional 38 weeks.
干预措施: Placebo to glimepiride (Drug)
Atorvastatin/Atorvastatin + Glimepiride
In Phase A, participants received atorvastatin 80 mg plus matching placebo to sitagliptin daily for 16 weeks. Participants continuing to Phase B received atorvastatin 80 mg plus matching placebo to sitagliptin plus glimepiride daily for an additional 38 weeks.
干预措施: Atorvastatin (Drug)
Atorvastatin/Atorvastatin + Glimepiride
In Phase A, participants received atorvastatin 80 mg plus matching placebo to sitagliptin daily for 16 weeks. Participants continuing to Phase B received atorvastatin 80 mg plus matching placebo to sitagliptin plus glimepiride daily for an additional 38 weeks.
干预措施: Placebo to sitagliptin (Other)
Atorvastatin/Atorvastatin + Glimepiride
In Phase A, participants received atorvastatin 80 mg plus matching placebo to sitagliptin daily for 16 weeks. Participants continuing to Phase B received atorvastatin 80 mg plus matching placebo to sitagliptin plus glimepiride daily for an additional 38 weeks.
干预措施: Metformin (open-label) (Drug)
Atorvastatin/Atorvastatin + Glimepiride
In Phase A, participants received atorvastatin 80 mg plus matching placebo to sitagliptin daily for 16 weeks. Participants continuing to Phase B received atorvastatin 80 mg plus matching placebo to sitagliptin plus glimepiride daily for an additional 38 weeks.
干预措施: Glimepiride (double-blind) (Drug)
Sitagliptin + Atorvastatin/Sitagliptin + Atorvastatin
In Phase A, participants sitagliptin 100 mg plus atorvastatin 80 mg daily for 16 weeks. Participants continuing to Phase B received sitagliptin 100 mg plus atorvastatin 80 mg plus matching placebo to glimepiride daily for an additional 38 weeks.
干预措施: Sitagliptin (Drug)
Sitagliptin + Atorvastatin/Sitagliptin + Atorvastatin
In Phase A, participants sitagliptin 100 mg plus atorvastatin 80 mg daily for 16 weeks. Participants continuing to Phase B received sitagliptin 100 mg plus atorvastatin 80 mg plus matching placebo to glimepiride daily for an additional 38 weeks.
干预措施: Atorvastatin (Drug)
Sitagliptin + Atorvastatin/Sitagliptin + Atorvastatin
In Phase A, participants sitagliptin 100 mg plus atorvastatin 80 mg daily for 16 weeks. Participants continuing to Phase B received sitagliptin 100 mg plus atorvastatin 80 mg plus matching placebo to glimepiride daily for an additional 38 weeks.
干预措施: Metformin (open-label) (Drug)
Sitagliptin + Atorvastatin/Sitagliptin + Atorvastatin
In Phase A, participants sitagliptin 100 mg plus atorvastatin 80 mg daily for 16 weeks. Participants continuing to Phase B received sitagliptin 100 mg plus atorvastatin 80 mg plus matching placebo to glimepiride daily for an additional 38 weeks.
干预措施: Glimepiride (open-label) (Drug)
Sitagliptin + Atorvastatin/Sitagliptin + Atorvastatin
In Phase A, participants sitagliptin 100 mg plus atorvastatin 80 mg daily for 16 weeks. Participants continuing to Phase B received sitagliptin 100 mg plus atorvastatin 80 mg plus matching placebo to glimepiride daily for an additional 38 weeks.
干预措施: Placebo to glimepiride (Drug)
结局指标
主要结局
Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 16
时间窗: Baseline and Week 16
Percent change from baseline was calculated as the Week 16 value minus the Week 0 value, divided by the Week 0 value ×100%.
Number of Participants Who Experienced at Least One Adverse Event
时间窗: Up to 56 weeks (including 2-week follow-up)
An 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 investigational product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the investigational product, is also an adverse event. Data presented exclude data following the initiation of glycemic rescue therapy.
Number of Participants Who Discontinued Study Drug Due to an Adverse Event
时间窗: Up to 54 weeks
An 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 investigational product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the investigational product, is also an adverse event. Data presented exclude data following the initiation of glycemic rescue therapy.
Change From Baseline in Hemoglobin A1C (A1C) at Week 16
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.
次要结局
- 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)
- Change From Baseline in Fasting Plasma Glucose (FPG) at Week 16(Baseline and Week 16)
- Percent Change From Baseline in Total Cholesterol at Week 16(Baseline and Week 16)
- Percent Change From Baseline in Triglycerides 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)
- Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) at Week 16(Baseline and Week 16)