A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Safety and Efficacy of KD026 in Combination With Metformin in Subjects With Type 2 Diabetes Mellitus
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 121
- 试验地点
- 10
- 主要终点
- Number of Subjects Experiencing Adverse Events as a Measure of Safety, Tolerability, and Efficacy
研究概览
简要总结
This study will compare the safety, tolerability and efficacy of the combination of KD026 and metformin compared to placebo and metformin on improving glycemic control in patients with type 2 diabetes mellitus.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Have type 2 diabetes, with finger stick HbA1c ≥ 7.0% and ≤ 11.0% at screening visit, and HbA1c via venipuncture ≥ 7.0% and ≤ 11.0 % at the Qualification visit
- •Have been on metformin for at least 12 weeks prior to screening visit and the metformin dose is not expected to change during the 4-week run-in period
- •Have a BMI of ≥ 27 kg/m2 and ≤ 45 kg/m2
- •Men, post-menopausal women (defined as not having a menstrual period for at least 1 year), surgically sterile women (for at least 1 year), or women of childbearing potential with a negative pregnancy test within the last 24 hours
- •Women of childbearing potential and men whose partners are of childbearing potential must agree to use two forms of accepted methods of contraception during the course of the study and for 1 month after their last dose of study drug. Effective birth control includes (a) IUD plus one barrier method; (b) on stable doses of hormonal contraception for at least 3 months (eg, oral, injectable, implant, transdermal) plus one barrier method; (c) 2 barrier methods. Effective barrier methods are male or female condoms, diaphragms, and spermicides (creams or gels that contain a chemical to kill sperm); or (d) a vasectomized partner
排除标准
- •Have type 1 diabetes
- •Taking antidiabetic medications other than or in addition to metformin
- •Have fasting plasma glucose > 270 mg/dL at screening visit
- •Have a serum creatinine ≥1.7 mg/dL or glomerular filtration rate <60 mL/min at screening visit
- •Have a history of diabetic retinopathy
- •Uncontrolled high blood pressure
- •Have a history of chronic liver disease and/or alanine transaminase (ALT) or aspartate transaminase (AST) >2.0 × the upper limit of normal (ULN) at screening visit.
- •Have a history of a malignant cancer (other than basal cell, localized cervical, or squamous cell carcinoma of the skin that has been removed)
- •Have a history or presence of gastrointestinal (GI) disease or major gastrointestinal surgery that, in the opinion of the investigator, could interfere with drug absorption
- •Currently using any of prohibited medications that cannot be stopped
- •Abuse alcohol (defined as an average weekly intake of greater than 21 units or an average daily intake of greater than 3 units [1 unit is equivalent to a half pint of beer, 1 serving of hard liquor, or one glass of wine]
- •History or presence of drug abuse according to Diagnostic and Statistical Manual of Mental Disorders V (DSM-V) criteria within the 2 years prior to screening visit
- •Have a 12-lead ECG at screening visit that, in the opinion of the investigator, have abnormalities that may compromise safety in this study, including a QTc(F) interval (QT interval data corrected using Fridericia's formula) of > 450 msec
- •Have a clinically significant abnormal laboratory result including thyroid-stimulating hormone (TSH) >1.5 × ULN at screening visit
- •Have a positive test for hepatitis B surface antigen (HBsAg), hepatitis C antibody/virus (HCV) or human immunodeficiency virus (HIV) antibodies at screening visit or a documented history of a positive result
- •Pregnant or lactating woman
- •Previously received KD026 (formerly named SLx-4090)
- •Participated in a trial with any investigational drug within 4 weeks prior to screening visit
研究组 & 干预措施
Cohort 1 100 mg KD026 BID
100 mg KD026 twice a day (BID) in combination with Metformin for 12 weeks
干预措施: KD026 (Drug)
Cohort 1 100 mg KD026 BID
100 mg KD026 twice a day (BID) in combination with Metformin for 12 weeks
干预措施: Metformin (Drug)
Cohort 2 150 mg KD026 BID
150 mg KD026 BID in combination with Metformin for 12 weeks
干预措施: KD026 (Drug)
Cohort 2 150 mg KD026 BID
150 mg KD026 BID in combination with Metformin for 12 weeks
干预措施: Metformin (Drug)
Cohort 3 200 mg KD026 BID
200 mg KD026 BID in combination with Metformin for 12 weeks
干预措施: KD026 (Drug)
Cohort 3 200 mg KD026 BID
200 mg KD026 BID in combination with Metformin for 12 weeks
干预措施: Metformin (Drug)
Cohort 4 100 mg KD026 TID
100 mg KD026 three times a day (TID) in combination with Metformin for 12 weeks
干预措施: KD026 (Drug)
Cohort 4 100 mg KD026 TID
100 mg KD026 three times a day (TID) in combination with Metformin for 12 weeks
干预措施: Metformin (Drug)
Cohort 1 Placebo
Matched Placebo Dose BID in combination with Metformin for 12 weeks
干预措施: Placebo (Drug)
Cohort 1 Placebo
Matched Placebo Dose BID in combination with Metformin for 12 weeks
干预措施: Metformin (Drug)
Cohort 2 Placebo
Matched Placebo Dose BID in combination with Metformin for 12 weeks
干预措施: Placebo (Drug)
Cohort 2 Placebo
Matched Placebo Dose BID in combination with Metformin for 12 weeks
干预措施: Metformin (Drug)
Cohort 3 Placebo
Matched Placebo Dose BID in combination with Metformin for 12 weeks
干预措施: Placebo (Drug)
Cohort 3 Placebo
Matched Placebo Dose BID in combination with Metformin for 12 weeks
干预措施: Metformin (Drug)
Cohort 4 Placebo
Matched Placebo Dose TID in combination with Metformin for 12 weeks
干预措施: Placebo (Drug)
Cohort 4 Placebo
Matched Placebo Dose TID in combination with Metformin for 12 weeks
干预措施: Metformin (Drug)
结局指标
主要结局
Number of Subjects Experiencing Adverse Events as a Measure of Safety, Tolerability, and Efficacy
时间窗: 12 Weeks
To assess the safety, tolerability, and efficacy (as measured by a 0.5%-1.5% decrease of HbA1c) of different dosages and dosing regimens of a combination of KD026 and metformin compared to placebo and metformin when administered for 3 months to subjects with type 2 diabetes mellitus
次要结局
- Changes in Body Mass Index (BMI)(12 Weeks)
- Changes in Serum Levels of Non-Esterified Free Fatty Acids(12 Weeks)
- Changes in AUC(12 Weeks)
- Changes in Fasting Plasma Glucose (FPG)(12 Weeks)
- Changes in Insulin(12 Weeks)
- Changes in Body Weight(12 Weeks)
- Changes in HOMA-IR(12 Weeks)
- Changes in Waist Circumference(12 Weeks)
- Changes in Plasma Levels of KD026(12 Weeks)
- Changes in Lipids(12 Weeks)
- Changes in Blood Pressure(12 Weeks)