dose escalation study to evaluate safety, tolerability, pharmacokinetics and pharmacodynamics of remd-477 in subjects with type 2 diabetes mellitus

Conditions: Type 2 Diabetes Mellitus; Diabetes

Summary: 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).

Eligibility criteria:
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.