Study to Evaluate the Safety, Tolerability and Efficacy of Three Dose Levels of Mitoglitazone in Type 2 Diabetic Patients
Condition: Type 2 Diabetes
Intervention: Mitoglitazone; Mitoglitazone; Mitoglitazone; Pioglitazone; Placebo
Intervention description: 50 mg capsules, once daily for 84 days; Mitoglitazone 100 mg capsules, once daily for 84 days; Mitoglitazone 150 mg capsules, once daily for 84 days; Pioglitazone 45 mg, once daily for 84 days; Placebo, once daily for 84 days
Intervention MeSH terms: Pioglitazone
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 356.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Diabetes

Summary:

      The purpose of this study is to evaluate the safety, tolerability and efficacy of three dose
      levels of Mitoglitazone™ (MSDC-0160) in patients with type 2 diabetes.
    

Eligibility criteria:

        Inclusion Criteria

          1. 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).

          2. Between the ages of 18-75 years, inclusive.

          3. 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.

          4. Body Mass Index (BMI) = 23 kg/m2 to 45 kg/m2 (inclusive).

          5. Willing and able to make a screening visit to the clinic and seven visits over a 21
             week period.

          6. 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

          1. Use of TZDs or diabetes medications other than metformin (generic or Glucophage®) 3
             months prior to screening.

          2. History of diabetic ketoacidosis or hyperosmolar non-ketotic coma.

          3. Fasting plasma glucose in excess of 240 mg/dl at screening

          4. 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.

          5. 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.

          6. History nephropathy, neuropathy, or retinopathy within 6 months of screening.

          7. Use of glucocorticoids (oral, injectible, intraarticular, or chronic inhaled) or
             weight-loss drugs within 3 months of randomization.

          8. Current or recurrent disease that may affect the action, absorption or disposition of
             the study treatment, or clinical or laboratory assessments.

          9. Current or history of severe or unstable disorder (medical or psychiatric) requiring
             treatment that may make the patient unlikely to complete the study.

         10. Febrile illness within the 5 days prior to the first dose.

         11. Known history of HIV, hepatitis B, or hepatitis C.

         12. Clinically significant findings on physical examination, including BP, pulse rate and
             12-lead ECG.

         13. Blood pressure greater than 160/100 mmHg. Patients with elevated BP (<160/100 mmHg)
             with or without current treatment will be allowed at the discretion of the Principal
             Investigator (PI) and primary care physician. Individuals with hypertension must have
             been stabilized to the current treatment regimen for at least 6 weeks prior to
             screening.

         14. Change in BP or lipid-lowering medication within 6 weeks or change in dose of
             metformin or thyroid replacement within 3 months prior to screening.

         15. Known or suspected intolerance or hypersensitivity to the study drugs, closely related
             compounds or any of their stated ingredients.

         16. History of alcohol or drug abuse within 6 months of Screening.

         17. Have participated in an investigational study or received an investigational drug
             within 30 days or 5 half-lives (whichever is longer) prior to study drug
             administration.

         18. Blood donation of 1 pint or more within 56 days of screening.

         19. Plasmapheresis or plasma donation within 30 days of screening.

         20. Single 12-lead ECG demonstrating a QTc >450 msec at Screening. A single repeat ECG may
             be done at the investigator's discretion.

         21. 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.

         22. Evidence of clinically relevant pathology that could interfere with the study results
             or put the patient's safety at risk.

         23. Malignancy, including leukemia and lymphoma (not including basal cell skin cancer)
             within the last 5 years.