NCT02445911已完成1 期
Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Ascending Oral Doses of KQ-791 in Subjects With Type 2 Diabetes
Kaneq Bioscience Limited3 个研究点 分布在 1 个国家目标入组 81 人开始时间: 2015年6月最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 81
- 试验地点
- 3
- 主要终点
- Difference in the Change From Baseline in Fasting Blood Glucose Between KQ-791 and Placebo
研究概览
简要总结
This study will consist of multiple ascending oral doses in up to 3 groups, for 29 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
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Have a diagnosis of Type 2 Diabetes Mellitus (T2DM)
- •Be an adult between the ages of 18 (19 for Lincoln site) and 70 years
- •Female participants must be of non-childbearing potential, and must be either 1) postmenopausal with amenorrhea for at least 1 year prior to the first dose and Follicle Stimulating Hormone (FSH) serum levels consistent with postmenopausal status, or 2) have undergone one of the following sterilization procedures at least 6 months prior to the first dose:
- •hysteroscopic sterilization
- •bilateral tubal ligation or bilateral salpingectomy
- •hysterectomy
- •bilateral oophorectomy
- •Non-vasectomized males must agree to use a condom with spermicide or abstain from sexual intercourse during the study until 100 days beyond the last dose of study drug. (No restrictions are required for a vasectomized male provided his vasectomy has been performed 4 months or more prior to first dosing. A male who has been vasectomized less than 4 months prior to first dosing must follow the same restrictions as a non-vasectomized male)
- •Males must agree to not donate sperm during the study and for 100 days following the last dose
- •Have an HbA1c value between 7.0-10.0%
- •Be on a stable treatment regimen of metformin, with or without diet/exercise, for at least 8 weeks
- •Weigh 60 kilograms (kg) or more at screening and have a body mass index (BMI) greater than or equal to (≥) 25.0 and less than or equal to (≤) 40.0 kilograms/meters squared (kg/m2)
- •Have laboratory test results within the normal range for T2DM population, or with abnormalities deemed clinically insignificant. Urine protein levels must be within normal limits
- •Absence of active diabetic retinopathy (Stage 2 or greater by the International Clinical Disease Severity Scale for Diabetic Retinopathy)
- •Are willing to comply with specific dietary restrictions (that is, [i] able to fast overnight for at least 8-12 hours on several days and [ii] able to consume the standard meals provided during specified confinement days)
- •Have given written consent to allow collection of samples for Peripheral Blood Mononuclear Cells (PBMC) analysis and for possible biomarkers/safety analysis
- •Have given written informed consent approved by the institutional review board (IRB) governing the site
排除标准
- •Are currently enrolled in a clinical trial involving an investigational product or off-label use of a drug or device, or are concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study
- •Participated (defined as the last dose of study drug) within 30 days prior to dosing in a clinical trial involving an investigational product or non-approved use of a drug with a short half-life or within 5 half-lives of an investigational product with a half-life longer than 6 days
- •- Have a (QTcF) greater than (>) 450 milliseconds (msec), or clinical significant hypokalemia, a family history of long QT syndrome or any abnormality in the 12-lead Electrocardiogram (ECG)
- •Abnormal blood pressure (sitting) defined as diastolic blood pressure > 95 or less than (<) 50 millimeter of mercury (mmHg) and/or systolic blood pressure > 160 or < 90 mmHg
- •Have a history or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs
- •Show evidence of regular use of known drugs of abuse and/or positive findings on urinary drug screening
- •Evidence of human immunodeficiency virus (HIV) infection, hepatitis B, hepatitis C and/or positive results at screening for the respective antibodies for HIV, hepatitis B surface antigen (HBsAg), or hepatitis C antibodies (HCV)
- •Have anemia that would interfere with the trial or have donated ≥500 mL of blood within 56 days before the first dose or have donated plasma within 7 days before the first dose or provided any blood donation within last 30 days
- •Have an average weekly alcohol intake that exceeds 14 units per week (males) and 7 units per week (females) [1 unit = 12 ounces (oz) or 360 mL of beer, 5 oz or 150 mL of wine, or 1.5 oz or 45 mL of distilled spirits] or are unwilling to stop alcohol consumption 48 hours prior to the first dosing and throughout the study
- •Consume more than 10 cigarettes per day or the equivalent or are unable or unwilling to adhere to restricted smoking policies
- •Have had >1 episode of documented severe hypoglycemia within last 6 months or are currently diagnosed as having hypoglycemia unawareness
- •Have any of the following clinical laboratory test results:
- •estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 (impaired renal function)
- •alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels > 1.5 times (x) the upper limit of normal (ULN)
- •triglycerides (TG) > 500 milligrams/deciliter (mg/dL)
- •Have used insulin or other glycemic control medications, except metformin, for diabetic control within 3 months
- •Intend to use non-steroidal anti-inflammatory drugs (except aspirin) and drugs known to prolong QT interval, herbal products, or vitamin supplements that change glucose levels. The following medications are allowed for participants:
- •drugs for treatment of hypertension or lipid disorders (except bile acid resins, niacin or fish oils), platelet inhibitors, and on stable dose for 12 weeks prior to first dose
- •thyroid replacement therapy, proton pump inhibitors, antidepressants, antihistamines, regularly taken over-the-counter (OTC) and anti-emetics that do not cause a corrected QT interval (QTc) prolongation, provided such drugs are not specifically excluded
- •hormonal replacement therapy
研究组 & 干预措施
KQ-791 Dose 1
Experimental
Single loading dose on day 1, followed by single doses on days 8, 15, 22, 29
干预措施: KQ-791 (Drug)
KQ-791 Dose 2
Experimental
Single loading dose on day 1, followed by a daily dose for 28 days
干预措施: KQ-791 (Drug)
KQ-791 Dose 3
Experimental
Single loading dose on day 1 or days 1-2, followed by a daily dose for 28 days
干预措施: KQ-791 (Drug)
Placebo
Placebo Comparator
Multiple ascending doses matching KQ-791 dose
干预措施: Placebo (Drug)
结局指标
主要结局
Difference in the Change From Baseline in Fasting Blood Glucose Between KQ-791 and Placebo
时间窗: Baseline to Day 29
Data table is change from baseline in Fasting Blood Glucose. Statistical Analysis includes results for difference in Change from baseline in Fasting Blood Glucose Between KQ-791 and Placebo.
Number of Participants With One or More Treatment-Emergent Adverse Events
时间窗: Baseline to Day 29
次要结局
- Change From Baseline in the Quantitative Insulin Sensitivity Check Index (QUICKI)(Baseline to Day 29)
- Change From Baseline in the Insulin Sensitivity Index (ISI)(Baseline to Day 29)
- Change From Baseline in Beta Cell Function(Baseline to Day 29)
- Change From Baseline in Disposition Index(Baseline to Day 29)
- Change From Baseline in the Hepatic Insulin Resistance Index(Baseline to Day 29)
- Change From Baseline in 7-point Average Blood Glucose(Baseline to Day 29)
- Change From Baseline in Postprandial Glucose(Baseline to Day 29)
- Change From Baseline in HbA1c(Baseline to Day 29)
- Area Under the Plasma Concentration-Time Curve From Time Zero to 24-hours Post-Dose (AUC0-24)(Pre-dose, 0.5, 1, 2, 4, 8, 12, and 24 hours post-dose)
- Maximum Observed Plasma Concentration (Cmax)(Pre-dose, 0.5, 1, 2, 4, 8, 12, and 24 hours post-dose)
- Time of the Maximum Measured Plasma Concentration (Tmax)(Pre-dose, 0.5, 1, 2, 4, 8, 12, and 24 hours post-dose)
- Area Under the Plasma Concentration Versus Time Curve (AUCtau)(Pre-dose, 0.5, 1, 2, 4, 8, 12, and 24 hours post-dose; Day 3, 8, 15, 22, 29, and up to 24 hours post-dose on Day 29)
- Maximum Observed Plasma Concentration at Steady-state (Cmax_ss)(Pre-dose, 0.5, 1, 2, 4, 8, 12, and 24 hours post-dose; Day 3, 8, 15, 22, 29, and up to 24 hours post-dose on Day 29)
- Time of the Maximum Measured Plasma Concentration at Steady-state (Tmax_ss)(Pre-dose, 0.5, 1, 2, 4, 8, 12, and 24 hours post-dose; Day 3, 8, 15, 22, 29, and up to 24 hours post-dose on Day 29)
- Apparent Terminal Elimination Half-life (t1/2)(Pre-dose, 0.5, 1, 2, 4, 8, 12, and 24 hours post-dose; Day 3, 8, 15, 22, 29, and up to 24 hours post-dose on Day 29)
- Accumulation Index (AI)(Pre-dose, 0.5, 1, 2, 4, 8, 12, and 24 hours post-dose; Day 3, 8, 15, 22, 29, and up to 24 hours post-dose on Day 29)
研究者
研究点 (3)
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