Safety and Efficacy of Once-Daily KRP-104 in Type 2 Diabetics With Inadequate Glycemic Control on Metformin Alone

Exclusion Criteria

• •1. History of type 1 diabetes mellitus or history of diabetic ketoacidosis or persistent hypoglycemia;
• •2. History or presence of alcoholism or drug abuse within the 2 years prior to dosing;
• •3. Typical consumption of greater than or equal to 10 drinks of alcohol weekly;
• •4. Presence of any of the following conditions:
• •* Significant renal impairment (glomerular filtration rate less than 60 mL/min);
• •* Diabetic gastroparesis;
• •* Active liver disease (other than asymptomatic nonalcoholic fatty liver disease), cirrhosis, or symptomatic gallbladder disease;
• •5. Fasting plasma glucose/blood glucose greater than 240 mg/dL (13.3 mmol/L) at Visit 3 (Week -2) (1 laboratory retest permitted);
• •6. Body mass index less than or equal to 20 kg/m2 and greater than or equal to 48 kg/m2;
• •7. Systolic blood pressure \<100 mmHg or \>160 mmHg and diastolic blood pressure \<50 mmHg or \>100 mmHg at Visit 3 (Note: medication to control blood pressure is allowed and should be optimized and stabilized prior to Visit 3);
• •8. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \>2 X the upper limit of normal (ULN) (1 laboratory retest permitted);
• •9. Creatine phosphokinase (CPK) greater than 2 X the ULN (if not explained by muscular trauma or exercise) (1 laboratory retest permitted);
• •10. Serum creatinine \>1.5 mg/dL for males (132.6 μmol/L) and 1.4 mg/dL for females (123.8 μmol/L);
• •11. Fasting triglycerides (TG) \>600 mg/dL (6.78 mmol/L) at Visit 3 (Week -2) (Note: diet/exercise and lipid-lowering medication to control elevated TG is allowed; medications should be optimized and stabilized prior to Visit 3);
• •12. Treatment with pioglitazone or rosiglitazone within the previous 10 weeks (Visit 1); treatment with incretin therapy (DPP-4 inhibitors or GLP-1 analogues) within the previous 4 weeks (Visit 1);
• •13. Treatment with any type of insulin (ie, injected or inhaled) within the previous 3 months;
• •14. Must meet other laboratory and Medical History clinical criteria. Please contact recruitment center for referrals