Safety, Tolerability, and Activity of ISIS 113715 in People With Type 2 Diabetes Mellitus Being Treated With Sulfonylurea

A Phase 2, Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Dose-Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Activity of ISIS 113715 Administered Daily in Patients With Type 2 Diabetes Mellitus Being Treated With Sulfonylurea

The aim of this study is to evaluate the safety, tolerability, and pharmacokinetics of two ISIS 113715 subcutaneous doses (15 mg and 30 mg/day) in combination with oral antidiabetic agents (OAD) versus OAD + placebo in patients with inadequately controlled type 2 diabetes, despite ongoing maximal treatment with OAD.

Inclusion Criteria:

• Male or female (post-menopausal and/or surgically sterile)
• Aged 18 to 70 years
• Diagnosed with type 2 diabetes mellitus of eight years or less in duration
• Being treated with OAD at stable maximum doses [defined as at least 10 mg/day glibenclamide (preferred), or 20 mg/day glipizide, with or without at least 1,500 mg/day metformin] for at least three months prior to screening
• Having fasting plasma glucose levels of 150-270 mg/dL and HbA1c levels of 7.5-11.0%

Exclusion Criteria:

• Greater than 3 severe hypoglycemic episodes within six months of screen
• Pregnant, breastfeeding, or intends to become pregnant
• Clinical signs or symptoms of liver disease, acute, or chronic hepatitis, or ALT greater than the upper limit of normal
• Positive hepatitis B surface antigen, hepatitis C antibody, or HIV test
• Patients with history of renal transplantation or renal dialysis or microalbuminuria defined as urine albumin > 200 mg/day
• History of insulin use within three months of screen
• History of diabetic ketoacidosis
• Treatment with any thiazolidinedione (e.g., rosiglitazone) within three months of screen
• History of lactic acidosis while on metformin therapy
• Complications of diabetes (e.g., neuropathy, nephropathy, and retinopathy)
• Clinically significant and currently active diseases
• Clinical significant abnormalities in medical history, physical examination, or laboratory examination