Study to Evaluate the Safety, Tolerability and Efficacy of Three Dose Levels of Mitoglitazone in Type 2 Diabetic Patients

Inclusion Criteria

• Males and females with Type 2 diabetes (fasting plasma glucose ≥126 mg/dL at screening, glycosylated hemoglobin [HbA1c] >7 and ≤10%, and Insulin C-peptide >1 ng/mL). Patients can be naïve to diabetes therapy or if taking metformin should be on a stable dose level for a period of at least 3 months prior to screening visit (no dose limit).
• Between the ages of 18-75 years, inclusive.
• Females should be either postmenopausal (at least 12 months since last menses) or surgically sterilized (bilateral tubal ligation or hysterectomy). Menopausal status will be verified by a follicle-stimulating hormone (FSH) test. If FSH levels are below 40 mIL/mL, some method of birth control must be used. Those with bilateral tubal ligation must also use a barrier method of birth control. In addition, all females must have a negative pregnancy test at Screen and Day 15 regardless of childbearing potential. Males with female partners of child-bearing potential must agree to use adequate contraceptive methods (including a condom, plus one other form of contraception) if engaging in sexual intercourse.
• Body Mass Index (BMI) = 23 kg/m2 to 45 kg/m2 (inclusive).
• Willing and able to make a screening visit to the clinic and seven visits over a 21 week period.
• Willing and able to sign an informed consent document indicating understanding the purpose of and procedures required for the study and willingness to participate in the study.

Exclusion Criteria

• Use of TZDs or diabetes medications other than metformin (generic or Glucophage®) 3 months prior to screening.
• History of diabetic ketoacidosis or hyperosmolar non-ketotic coma.
• Fasting plasma glucose in excess of 240 mg/dl at screening
• History of heart failure (including CHF) or previous cardiovascular event (myocardial infarct, by-pass surgery, or PTCA) within the past 6 months prior to screening.
• ALT and/or AST levels that are twice the upper limit of normal; bilirubin levels that exceed 2 mg/dL; serum creatinine >1.5 mg/dL in men or > 1.4 mg/dL in women.
• History nephropathy, neuropathy, or retinopathy within 6 months of screening.
• Use of glucocorticoids (oral, injectible, intraarticular, or chronic inhaled) or weight-loss drugs within 3 months of randomization.
• Current or recurrent disease that may affect the action, absorption or disposition of the study treatment, or clinical or laboratory assessments.
• Current or history of severe or unstable disorder (medical or psychiatric) requiring treatment that may make the patient unlikely to complete the study.
• Febrile illness within the 5 days prior to the first dose.
• Known history of HIV, hepatitis B, or hepatitis C.
• Clinically significant findings on physical examination, including BP, pulse rate and 12-lead ECG.
• Blood pressure greater than 160/100 mmHg. Patients with elevated BP ( 450 msec at Screening. A single repeat ECG may be done at the investigator's discretion.
• Any surgical or medical condition which may significantly alter the absorption of any drug substance including, but not limited to, any of the following: history of major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, bowel resection, gastric bypass, gastric stapling, or gastric banding, currently active inflammatory bowel syndrome.
• Evidence of clinically relevant pathology that could interfere with the study results or put the patient's safety at risk.
• Malignancy, including leukemia and lymphoma (not including basal cell skin cancer) within the last 5 years.