Study of Subcutaneous Doses of HIP2B in Subjects With Type 2 Diabetes Mellitus Treated With Metformin

A Randomized, Double-blind, Placebo-controlled Study of the Effect of 49 Days of Treatment With Repeated Subcutaneous Doses of HIP2B to Assess Safety, Tolerability and Measures of Islet β-cell Function in Subjects With Type 2 Diabetes Mellitus Treated With Metformin

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.

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.