single-dose study to evaluate safety, tolerability, and pharmacodynamics of remd-477 in subjects with type 1 diabetes mellitus

Conditions: Type 1 Diabetes Mellitus; Diabetes

Summary: this is a randomized, placebo-controlled, double-blind study to evaluate safety, tolerability and pharmacodynamics of remd-477 in subjects who have type 1 diabetes and are currently receiving insulin treatment. this proof of concept study will determine whether glucagon receptor blockade using a single dose remd-477 can improve short-term glucose homeostasis in people with type 1 diabetes.

the study will be conducted at two sites in the united states, and approximately 20 subjects with type 1 diabetes will be enrolled. eligible subjects will be admitted to the clinical research unit, to carefully monitor blood glucose; and establish the baseline insulin requirement for maintaining targeted normoglycemia (postabsorptive: 90-120 mg/dl; and postprandial: \<180 mg/dl). the patients will then be subjected to a hyperglycemic period (250-300 mg/dl) by a stepwise reduction in insulin infusion. after receiving a single sc dose of remd-477 or matching placebo in a double-blinded fashion, all subjects will be assessed for the post-treatment 24-hour insulin requirement needed to maintain targeted normoglycemia (postabsorptive: 90-120 mg/dl; and postprandial: \<180 mg/dl); and to be monitored closely for safety, tolerability and targeted glycemic control, for a 48-hr period. after the in-patient residency period, subjects will return to the clinic for weekly out-patient safety follow-up visits for 8 weeks.

Eligibility criteria:
inclusion criteria: * men and women between the ages of 18 and 60 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. females of child bearing potential must agree to use two methods of contraception; * male subjects must be willing to use clinically acceptable method of contraception during the entire study; * body mass index between 18.5 and 26.9 kg/m2, inclusive, at screening; * diagnosed with type 1 diabetes for greater than 2 years, based on clinical history or as defined by the current american diabetes association (ada) criteria; * hba1c ≥6.0 % but \<9.0 % at screening; * fasting c-peptide \<0.2 ng/ml; * current use of insulin pump and willing to use continuous glucose monitoring (cgm) system (e.g. dexcom) throughout the entire study; * alt and/or ast within \<1.5x uln at screening; * serum amylase and lipase within normal limits at screening; * able to provide written informed consent approved by an institutional review board (irb). exclusion criteria: * history or evidence of clinically-significant disorder or condition that, in the opinion of the investigator, would pose a risk to subject safety or interfere with the study evaluation, procedures, or completion; * significant organ system dysfunction (e.g., clinically significant pulmonary or cardiovascular disease, anemia \[hemoglobin \<10.0 g/dl\], and renal dysfunction \[egfr \<90 ml/1.73m2/min\]); * any severe symptomatic hypoglycemic event associated with a seizure or requiring help from other people or medical facility in the past 6 months; * current or recent (within 1 month of screening) use of diabetes medications other than insulin; * use of steroids and/or other prescribed or over-the-counter medications that are known to affect the outcome measures in this study or known to influence glucose metabolism; * smokes tobacco; * known sensitivity to mammalian-derived drug preparations, recombinant protein-based drugs or to humanized or human antibodies; * history of illegal drug use or alcohol abuse within the last 6 months or a positive drug urine test result at screening; * history of pancreatitis, pancreatic neuroendocrine tumors or multiple endocrine neoplasia; * history of pheochromocytoma, or family history of familial 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 \>500 ml within 30 days of day 1; * women who are pregnant or lactating/breastfeeding; * regular exercise \>120 min/week within 14 days of day 1; * unable or unwilling to follow the study protocol or who are non-compliant with screening appointments or study visits; * family history of multiple endocrine neoplasia. other inclusion and exclusion criteria may apply.