study of subcutaneous doses of hip2b in subjects with type 2 diabetes mellitus treated with metformin

Conditions: Type 2 Diabetes Mellitus

Summary: hip2b is being developed for the treatment of type 1 and type 2 diabetes mellitus. the purpose of this study is to investigate the safety and tolerability of repeat doses of hip2b in subjects with type 2 diabetes mellitus. the study will also assess whether islet β-cell number and function will increase over time in response to repeat hip2b injections.


Eligibility criteria:
inclusion criteria: * adults aged 30 to 65 years, inclusive * males and females * diagnosis of type 2 diabetes mellitus prior to screening meeting the following criteria: 1. body mass index \<45 kg/m2 2. hba1c value of \> 6.5 to \<9.5% 3. c-peptide ≥1.0 ng/ml 4. on a stable dose of metformin for 12 weeks * ability to provide written informed consent and be willing to comply with scheduled visits, treatment plan, laboratory tests and other study procedures exclusion criteria: * history of any of the following: type 1 diabetes mellitus, diabetic ketoacidosis, an episode of severe hypoglycemia (defined as a change in mental status requiring assistance) during the prior 30 days * fpg \>260 mg/dl at time of randomization * current or chronic use (within past 12 weeks) of insulin, or insulin secretagogues including: sulfonylureas, glp-1 analogs, dpp-4 inhibitors, meglitinides, α-glucosidase inhibitors, pioglitazone, or rosiglitazone * glomerular filtration rate (gfr) \<60 as calculated using the modified diet in renal disease equation at screening * alt, ast or total bilirubin \> 2 x uln * serum amylase concentration \> 1.5xuln or serum lipase concentration \>2xuln * positive test result for glutamic acid decarboxylase antibodies (gada). * the presence of a clinically significant abnormality on resting electrocardiogram (ecg) * positive hiv, hepatitis b (hbsag), or positive hepatitis c (hcv ab) test at screening * history of clinically significant renal, hepatic, cardiovascular, neurological, or gastrointestinal disease that could impact patient safety in the investigator's opinion * serum triglycerides \>500 mg/dl * presence or history of cancer within the past 5 years with the exception of adequately treated localized basal cell skin cancer or in situ uterine cervical cancer * history of weight loss \> 5% in the 8 weeks prior to randomization or subject is on a weight loss program and is not in the maintenance phase * use of any weight loss medication within 8 weeks of randomization * uncontrolled hypertension defined as blood pressure \>160/100 mmhg, using an appropriately sized cuff, at rest * history or evidence of multiple organ autoimmune disorders * history of thyroid dysfunction other that hypothyroidism treated with stable dose of thyroid hormone and euthyroid at screening * history or presence of acute or chronic pancreatitis or symptomatic recurrent gallstones * has undergone surgery within 6 months of screening or plans to undergo surgery during the study period * use of parenterally administered proteins or antibodies within 12 weeks of screening. (note: influenza vaccine will be allowed.) * prior exposure to any investigational agent or participation in an investigational trial within 30 days prior to day 1 * blood loss or blood donation \>500 ml in the 2 months prior to screening. * use of systemic long-acting corticosteroids within two months or prolonged use (more than one week) of other systemic corticosteroids or inhaled corticosteroids (if daily dosage is \>1000 mcg equivalent beclomethasone) within 30 days prior to screening visit. * drugs with the potential to affect (either increasing or decreasing) endogenous insulin secretion or insulin sensitivity including corticosteroids (as detailed above), β-adrenergic blockers, beta-adrenergic agonists, quinine, thiazide or thiazide-like diuretics, calcineurin inhibitors, niacin, anti-psychotic or antidepressant drugs, somatostatin analogs, growth hormone, weight-reducing drugs (e.g. orlistat, phentermine and topiramate extended-release, lorcaserin). stable doses of agents commonly required by subjects with t2dm including angiotensin converting enzyme inhibitors, angiotensin ii receptor blockers, statins, fibrates, and aspirin (\<100 mg daily) will be permitted at the discretion of the investigator. * a serious adverse reaction or hypersensitivity to any drug, unless reaction deemed irrelevant to the study by the investigator and sponsor. * history of alcohol abuse or drug abuse within the previous 12 months. no history of medical or recreational use of marijuana within previous 12 months. * a history of smoking more than one-half a pack of cigarettes per day within last 12 months * history of stroke, transient ischemic attack or myocardial infarction within 6 months prior to screening. * history of new york heart association class ii-iv heart failure prior to screening.

Keywords: type 2 diabetes mellitus hip2b placebo islet β cell