1. Clinically significant systemic diseases/conditions that, in the opinion of the Investigator, could negatively affect the safety of the patient during the study on a as determined on a case by case basis (e.g., unstable medical status including uncontrolled blood pressure, cardiovascular disease, uncontrolled liver disease, glycemic control or significant renal disease, defined as a history of chronic renal failure requiring dialysis or kidney transplant, hepatic, pulmonary, gastrointestinal or neurological diseases, cancer or BMI).