A Study to Evaluate the Efficacy and Safety of Cyclo-Z in Patients With Obese Type 2 Diabetes

A Multicenter, Randomized, Double-blind, Placebo-controlled, Phase 2 Study to Evaluate the Efficacy and Safety of Cyclo-Z in Patients With Obese Type 2 Diabetes

This is a double-blind, randomized, placebo-controlled, parallel-group comparison study to evaluate the efficacy and safety of Cyclo-Z for the treatment of subjects with obese type 2 diabetes.

The study will consist of 3 phases:

• Screening phase (2 weeks)
• Treatment phase (12 weeks)
• Follow-up phase (2 weeks)

Following a 2-week screening period, subjects who meet all inclusion and exclusion criteria will be randomly assigned into one of the following treatment arms:

• Dose A: Cyclo-Z containing 23 mg zinc plus 3 mg CHP - 16 subjects
• Dose B: Cyclo-Z containing 23 mg zinc plus 9 mg CHP - 16 subjects
• Dose C: Cyclo-Z containing 23 mg zinc plus 15 mg CHP - 16 subjects
• Dose D: Placebo - 16 subjects

The assigned dose will be orally administered to subjects once a day before bedtime for 12 consecutive weeks. After the randomization at Week 0 (Visit 2), subjects will visit their respective trial sites at Weeks 2, 4, 6, 8, 10, 12, and 14 (Visits 3, 4, 5, 6, 7, 8, and 9).

Inclusion Criteria:

1. Males or females aged 18 or older.
2. Subjects diagnosed with type 2 diabetes mellitus according to the American Diabetes Association (ADA) criteria.
3. Subjects treated with stable doses of insulin and/or other hypoglycemic agent(s) for type 2 diabetes mellitus for at least 2 months prior to randomization.
4. Subjects whose fasting blood glucose levels are reasonably stable for at least 2 months prior to randomization and during the 2-week screening period.
5. Subjects who have Hemoglobin A1c levels of 7.5 to 10.0 % at Screening.
6. Subjects whose BMI is 30 or above.
7. Subjects who can give written informed consent.

Exclusion Criteria:

1. Subjects who have any DM-related end-organ damages.

2. Subjects who have a history of diabetic ketoacidosis or hyperosmolar non-ketotic coma.

3. Subjects who have any disease likely to limit life span and/or increase risks of interventions such as:

   • Carotid B-mode ultrasound test results indicating clinically significant stenosis in the common carotid arteries requiring intervention by angioplasty or resection.
   • Cancer treatment in the past 5 years, with the exception of cancers which have been cured, and carry a good prognosis.
   • Infectious disease: HIV positivity, active tuberculosis, or pneumonia.

4. Subjects who have any of the following conditions related to cardiovascular disease:

   • Hospitalization for the treatment of heart disease in the past 12 months.
   • New York Heart Association Functional Class > 2.
   • Left Bundle branch block on ECG at Screening.
   • Third degree atrioventricular block on ECG at Screening.
   • Uncontrolled hypertension with average systolic blood pressure of > 160 mmHg or diastolic blood pressure > 95 mmHg at Screening and Baseline.
   • Pulse rate > 95 beats per minute at Screening and Baseline.
   • Stroke or transient ischemic attack in the past 12 months.

5. Subjects who have any of the following conditions related to gastrointestinal disease:

   • Chronic hepatitis or cirrhosis.
   • Episode of alcoholic hepatitis or alcoholic pancreatitis in the past 2 months.
   • Inflammatory bowel disease requiring treatment in the past 12 months.
   • Significant abdominal surgery (e.g., gastrectomy, gastric bypass) in the past 2 months.

6. Subjects who have serum creatinine > 1.5 mg/dL for male or > 1.4 mg/dL for female.

7. Subjects who have chronic obstructive airway disease or asthma requiring daily therapy or home use oxygen.

8. Subjects who have hematocrit < 36.0% for male or < 33.0% for female.

9. Subjects who have any of the following conditions or behaviors likely to affect the conduct of the study:

   • Weight loss of > 10% in the past 6 months.
   • Unable to walk without assisted device.
   • Major psychiatric disorder which would impede conduct of the research.
   • Excessive alcohol intake (i.e., more than 2 drinks/day).

10. Subjects who take any of the following medications:

    • Psychoactive agents such as monoamine oxidase inhibitors and antidepressants (e.g., lithium, Prozac, Zoloft, Serzone, Paxil, Effexor).
    • Any other medications that may pose harm to the subject.

11. Female subjects who have a positive serum pregnancy test at Screening, plan a pregnancy during study period, or are breast feeding.

12. Female subjects who don't meet any of the following criteria:

    • Surgically sterile (i.e., have had bilateral tubal ligation, hysterectomy, or bilateral oophorectomy) at least 6 months before randomization.
    • Post-menopausal for at least 12 months prior to Screening.
    • If sexually active, they should use oral contraceptives, double barrier contraception (e.g., condom with spermicide), intrauterine device, or other methods approved by the Sponsor.