A Randomized, Placebo-controlled, Double-blind, Dose Escalation Study to Evaluate Safety, Tolerability, Pharmacokinetics (PK) and Pharmacodynamics (PD) of Single and Repeated Subcutaneous (SC) Doses of REMD-477 in Subjects With Type 2 Diabetes Mellitus

REMD Biotherapeutics, Inc.3 个研究点分布在 1 个国家目标入组 75 人开始时间: 2015年9月最近更新: 2018年4月10日

适应症

干预措施

试验速览

阶段: 1 期
状态: 已完成
发起方: REMD Biotherapeutics, Inc.
入组人数: 75
试验地点: 3
主要终点: Number of treatment emergent adverse events per subject, including changes in vital signs, physical and neurological examinations, laboratory safety tests and ECGs

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

This is a randomized, placebo-controlled, double-blind, dose escalation study to evaluate safety, tolerability, PK and PD of single and repeated SC doses of REMD-477 in Type 2 diabetic subjects. The study will be conducted at multiple sites in the United States and will enroll approximately 102 subjects with Type 2 diabetes who are either treatment-naïve, controlled with diet and exercise or treated with oral antidiabetic medications.

详细描述

The study will consist of three parts: Part A - Dose Escalation, Part B - Adaptive Dose Cohort, and Part C - REMD-477 in Combination with Metformin. Part A includes 5 cohorts that will be enrolled and dosed sequentially at escalating doses. Each cohort will consist of 12 subjects randomized in a 3:1 (active: placebo) fashion. Part B includes a single dose cohort that will enroll 12 subjects (9 on active treatment and 3 on placebo) with dose level and frequency determined by a Dose Level Review Meeting (DLRM)Committee. Part C includes 2 cohorts of T2DM patients currently treated with metformin alone, and each cohort will consist of 15 subjects (10 on active treatment and 3 on placebo).

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: Triple (Participant, Investigator, Outcomes Assessor)

入排标准

年龄范围: 18 Years 至 65 Years（Adult, Older Adult）
性别: All
接受健康志愿者: 否

入选标准

•Men and women between the ages of 18 and 65 years old, inclusive, at the time of screening;
•Females of non-child bearing potential must be ≥1 year post-menopausal (confirmed by a serum follicle-stimulating hormone (FSH) levels ≥ 40 IU/mL) or documented as being surgically sterile, and females of child bearing potential must use two medically acceptable methods of contraception;
•Male subjects must be willing to use clinically acceptable contraception during treatment and for 2 months after the last administration of REMD-477;
•Normal or clinically-acceptable physical examination, laboratory test values, and 12-lead ECG (reporting heart rate and PR, QRS, QT, and QTcF) at screening;
•Body mass index between 23 and 40 kg/m2, inclusive, at screening;
•Diagnosed with Type 2 diabetes as defined by the current American Diabetes Association (ADA) criteria;
•Subjects in Parts A and B only: Treatment-naive, controlled with diet and exercise, or treated with oral antidiabetic medications and willing to wash-out and discontinue oral medications during the study;
•Fasting plasma glucose 126 - 270 mg/dL (7-15 mM), inclusive, at screening and at re-test on Day -1;
•Subjects in Parts A and B only: Screening HbA1c of 7.0-10 % inclusive for subjects not currently taking any oral antidiabetic medications, or 6.5-9.5% for subjects receiving acceptable oral antidiabetic medications;
•Subjects in Part C only: Screening HbA1c of 7.5-10 % inclusive for subjects on stable doses of metformin.

排除标准

•History of drug or alcohol abuse within the last 6 months or a positive illegal drug urine test result;
•History or family history of pancreatic neuroendocrine tumors or multiple endocrine neoplasia;
•History or family history of pheochromocytoma;
•Known or suspected susceptibility to infectious disease (eg, taking immunosuppressive agents or has a documented inherited or acquired immunodeficiency);
•Positive for human immunodeficiency virus (HIV) antibodies, hepatitis B surface antigen (HbsAg), or hepatitis C antibodies (HepC Ab);
•Participation in an investigational drug or device trial within 30 days of screening or within 5 times the half-life of the investigational agent in the other clinical study, if known, whichever period is longer;
•Blood donor, or blood loss>300 mL, within 30 days of Day 1;
•Recent use (6 weeks prior to Screening) of thiazolidinediones, >half-maximal dose sulfonylurea agent therapy, or any injectable antidiabetic agents (exenatide and other injectable GLP-1 agonists, insulin and insulin analogs, etc.);
•Other gastrointestinal, cardiac, renal and CNS (i.e. hypoglycemia unawareness) conditions specific to diabetes that would pose additional risk to subject's safety or interfere with the study evaluation, procedures or completion;
•Lipid panel profiles of non-HDL-C (total cholesterol minus HDL-C) >219 mg/dL, LDL-C >189 mg/dL, and/or fasting triglycerides >499 mg/dL;
•Female subject is pregnant or breastfeeding.
•Other inclusion and exclusion criteria may apply.