Safety, Tolerability and Efficacy of ISIS-GCCRRx in Type 2 Diabetes

A Randomized, Double Blind, Placebo-Controlled, Phase 2 Study to Assess the Safety, Tolerability and Efficacy of ISIS 426115 (an Antisense Glucocorticoid Receptor Antagonist) Administered Subcutaneously Once Weekly for 6 Weeks to Patients With Type 2 Diabetes Mellitus Being Treated With Metformin

The purpose of this study is to evaluate the efficacy, safety and tolerability of ISIS-GCCRRx in combination with metformin versus placebo + metformin

Inclusion Criteria:

• Male or female, age 18 to 75
• BMI greater than or equal to 25
• HbA1c greater than or equal to 7.5% and less than or equal to 10.5%
• Type 2 Diabetes Mellitus and on stable dose of oral metformin
• Agree to conduct home-based (fasted) blood glucose testing as directed

Exclusion Criteria:

• Clinically significant abnormalities in medical history or physical exam
• Show evidence of uncorrected hypothyroidism or hyperthyroidism hormone results
• History of renal transplantation or renal dialysis
• History of liver disease
• History of greater than 3 episodes of severe hypoglycemia within 6 months of screening
• Use of oral anti-diabetic medication other than metformin within 3 months of screening
• Use of medications that may affect plasma glucose levels (including systemic glucocorticoids), systemic steroids, corticosteroids, antiglucocorticoid therapies including mifepristone and ketoconazole (topical cream and systemic), immunosuppressive medications, somatostatin analogues or ACTH therapy within 3 months of screening
• History of diabetic ketoacidosis
• Current or previous diagnosis of Gilbert's disease
• Any other significant illness or condition that may interfere with the patient participating or completing the study
• Inability or unwillingness to comply with protocol or study procedures