Dose Escalation Study to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of REMD-477 in Subjects With Type 2 Diabetes Mellitus
Dose Escalation Study to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of REMD-477 in Subjects With Type 2 Diabetes Mellitus
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.
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).
Inclusion Criteria:

 -  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.

 Exclusion Criteria:

 -  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.