A Randomized, Double-Blind, Placebo-Controlled With Active Comparator, 12-Week Study of DS-8500a in Subjects With Type 2 Diabetes Mellitus on Metformin
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 298
- 主要终点
- Change From Baseline in Glycated Hemoglobin (HbA1c) at Week 12
研究概览
简要总结
The hypothesis of this Phase 2, 12-week study, is that DS-8500a will improve glycemic control relative to placebo, based on changes in HbA1c, with acceptable safety and tolerability, in patients with Type 2 Diabetes Mellitus (T2DM) who are treated with metformin.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Able to provide written informed consent and adhere to the study visit schedule and treatment
- •Diagnosed with Type 2 diabetes mellitus as defined in the American Diabetes Association Standards of Medical Care in Diabetes 2015
- •Male or female ≥ 18 and ≤ 70 years of age
- •Screening fasting C-peptide > 0.5 ng/mL
- •Women of child bearing potential (WOCBP) must be willing to use double-barrier contraception for the entire study
- •WOCBP must have a negative pregnancy test (human chorionic gonadotropin, beta subunit [βhCG]) before entering the Lead-in Period
- •Body mass index ≥ 25 kg/m2 and ≤ 45 kg/m2 at the Screening Visit
- •On stable (≥ 8 weeks) metformin monotherapy ≥ 1000 mg/day
- •Screening HbA1c ≥ 7.0% and ≤ 10%
- •Taking ≥ 80% and ≤ 120% of both dispensed DS-8500a placebo tablets and sitagliptin placebo capsules during the Lead-in Period
排除标准
- •History of type 1 diabetes and/or history of ketoacidosis
- •History of insulin use for > 2 weeks within 2 months prior to the Screening Visit
- •Two or more readings of fasting Self-monitoring of Blood Glucose (SMBG) > 240 mg/dL or worsening symptoms of hyperglycemia with one SMBG level of > 240 mg/dL during the second week of Lead-in Period, confirmed by laboratory measurement
- •Screening hemoglobin <12 g/dL for males and <11 g/dL for females
- •Blood donation within 2 months prior to the Screening Visit or plans to donate blood or blood products during the study
- •Subjects after bariatric surgery or any gastric bypass
- •Screening thyroid stimulating hormone (TSH) levels not within normal range (based on reference laboratory values )
- •Screening Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST) > 2.0 x upper limit of normal (ULN), and/or total bilirubin > 1.5 x ULN. If a subject has total bilirubin > 1.5 ULN, unconjugated and conjugated bilirubin fractions should be analyzed and only subjects documented to have Gilbert's syndrome may be enrolled
- •Screening Serum creatinine ≥ 1.5 mg/dL for males and ≥ 1.4 mg/dL for females, or creatinine clearance (CrCl) < 50 mL/min for both males and females
- •Screening Creatine kinase (CK) > 3.0 × ULN
- •History of unstable angina, myocardial infarction, cerebrovascular accident, transient ischemic attack, peripheral arterial event or any revascularization procedure during the 6 months prior to the Screening Visit or planned vascular procedures or surgery during study period
- •History of congestive heart failure (CHF)
- •Exclusionary concomitant medications:
- •a. Eight weeks prior to screening and throughout the duration of the study:
- •Any diabetes medication other than metformin; any prescription or over the counter medication for weight-loss.
- •Systemic corticosteroids (including nasal and inhaled), with the exception of use of topical and ophthalmic corticosteroids.
- •Rosuvastatin > 20 mg daily. b. During treatment periods, additional medications will be prohibited based on potential drug-drug interaction (DDI) (see Section 5.6)
- •Subjects with anticipated interruption in metformin or study drug use during the course of the clinical trial (e.g., due to an imaging procedure involving iodinated contrast media)
- •Subjects in whom treatment with sitagliptin 100 mg is contraindicated ( e.g., known hypersensitivity or intolerance to sitagliptin) or may not be medically advisable (e.g., history of pancreatitis)
- •Abuse of or dependence on prescription medications, illicit drugs, or alcohol within the last 1 year
- •Any history of a malignancy other than basal cell carcinoma within the past 5 years
- •Pregnancy or breast-feeding, or intent to become pregnant during the study period
- •Known (or evidence of) infection with human immunodeficiency virus
- •Any condition, laboratory abnormality, or concomitant therapy which, in the opinion of the Investigator, might pose a risk to the subject or make participation not in the subject's best interest
- •Subject is currently enrolled in or has not yet completed at least 30 days since ending another investigational device or drug study or is receiving other investigational agents
- •A direct or familial relationship with the Sponsor, Investigator, or site personnel affiliated with the study
研究组 & 干预措施
DS-8500a 25mg
One DS-8500a 25 mg tablet, 2 placebo tablets, and one placebo capsule in a once-daily oral dose
干预措施: DS-8500a 25mg (Drug)
DS-8500a 25mg
One DS-8500a 25 mg tablet, 2 placebo tablets, and one placebo capsule in a once-daily oral dose
干预措施: Placebo Tablet (Drug)
DS-8500a 25mg
One DS-8500a 25 mg tablet, 2 placebo tablets, and one placebo capsule in a once-daily oral dose
干预措施: Placebo Capsule (Drug)
DS-8500a 50 mg
Two DS-8500a 25 mg tablets, 1 placebo tablet, and one placebo capsule in a once-daily oral dose
干预措施: DS-8500a 25mg (Drug)
DS-8500a 50 mg
Two DS-8500a 25 mg tablets, 1 placebo tablet, and one placebo capsule in a once-daily oral dose
干预措施: Placebo Tablet (Drug)
DS-8500a 50 mg
Two DS-8500a 25 mg tablets, 1 placebo tablet, and one placebo capsule in a once-daily oral dose
干预措施: Placebo Capsule (Drug)
DS-8500a 75 mg
Three DS-8500a 25 mg tablets and one placebo capsule in a once-daily oral dose
干预措施: DS-8500a 25mg (Drug)
DS-8500a 75 mg
Three DS-8500a 25 mg tablets and one placebo capsule in a once-daily oral dose
干预措施: Placebo Capsule (Drug)
Placebo
Three placebo tablets and one placebo capsule in a once-daily oral dose
干预措施: Placebo Tablet (Drug)
Placebo
Three placebo tablets and one placebo capsule in a once-daily oral dose
干预措施: Placebo Capsule (Drug)
Sitagliptin 100 mg
Three placebo tablets and one sitagliptin 100 mg over-capsule in a once-daily oral dose
干预措施: Sitagliptin 100 mg (Drug)
Sitagliptin 100 mg
Three placebo tablets and one sitagliptin 100 mg over-capsule in a once-daily oral dose
干预措施: Placebo Tablet (Drug)
结局指标
主要结局
Change From Baseline in Glycated Hemoglobin (HbA1c) at Week 12
时间窗: Baseline, Week 12
Glycated hemoglobin is a form of hemoglobin that is measured primarily to identify the three-month average glucose concentration in the blood. Target HbA1c for Type 2 diabetics was less than 7% at the time of this trial. Negative scores show improvement from baseline.
次要结局
- Change From Baseline in HDL-C at Week 12(Baseline, Week 12)
- Change From Baseline in AUC0-3h of PG in Response to the MMTT at Week 12(Baseline, Week 12)
- Change From Baseline in Fasting Plasma Glucose (FPG) at Week 4(Baseline, Week 4)
- Count of Participants With HbA1c Less Than 7.0% at Week 12(Week 12)
- Change From Baseline in Maximum Concentration (Cmax) of PG in Response to MMTT at Week 4(Baseline, Week 4)
- Change From Baseline in LDL-C at Week 12(Baseline, Week 12)
- Change From Baseline in Non-HDL-C at Week 12(Baseline, Week 12)
- Change From Baseline in Fasting Plasma Glucose (FPG) at Week 2(Baseline, Week 2)
- Change From Baseline in Total Cholesterol (TC) at Week 12(Baseline, Week 12)
- Change From Baseline in Area-Under-the Curve 0-3 Hours (AUC0-3h) of Plasma Glucose (PG) in Response to the Mixed Meal Tolerance Test (MMTT) at Week 4(Baseline, Week 4)
- Change From Baseline in Cmax of PG in Response to MMTT at Week 12(Baseline, Week 12)
- Change From Baseline in Triglycerides at Week 12(Baseline, Week 12)
- Change From Baseline in Fasting Plasma Glucose (FPG) at Week 8(Baseline, Week 8)
- Change From Baseline in Fasting Plasma Glucose (FPG) at Week 12(Baseline, Week 12)