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

Study Overview
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Brief Summary
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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).

Official Title
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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

Conditions
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Diabetes Mellitus Type 2 in Obese

Intervention / Treatment
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* Drug: Cyclo-Z
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or females aged 18 or older. Subjects diagnosed with type 2 diabetes mellitus according to the American Diabetes Association (ADA) criteria. 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. Subjects whose fasting blood glucose levels are reasonably stable for at least 2 months prior to randomization and during the 2-week screening period. Subjects who have Hemoglobin A1c levels of 7.5 to 10.0 % at Screening. Subjects whose BMI is 30 or above. Subjects who can give written informed consent. Exclusion Criteria: Subjects who have any DM-related end-organ damages. Subjects who have a history of diabetic ketoacidosis or hyperosmolar non-ketotic coma. 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. 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. 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. Subjects who have serum creatinine > 1.5 mg/dL for male or > 1.4 mg/dL for female. Subjects who have chronic obstructive airway disease or asthma requiring daily therapy or home use oxygen. Subjects who have hematocrit < 36.0% for male or < 33.0% for female. 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). 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. Female subjects who have a positive serum pregnancy test at Screening, plan a pregnancy during study period, or are breast feeding. 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose A<br>Cyclo-Z containing 23 mg zinc plus 3 mg CHP | Drug: Cyclo-Z<br> <br> |
| Experimental: Dose B<br>Cyclo-Z containing 23 mg zinc plus 9 mg CHP | Drug: Cyclo-Z<br> <br> |
| Experimental: Dose C<br>Cyclo-Z containing 23 mg zinc plus 15 mg CHP | Drug: Cyclo-Z<br> <br> |
| Placebo Comparator: Dose D<br>Placebo | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of HbA1c Level From Baseline | Change in HbA1c from Day 1 to Week 12 | 12 weeks | 
| Change of Body Weight From Baseline | Change in body weight from Day 1 to Week 12 | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of Fasting Plasma Glucose Level From Baseline | Change in fasting plasma glucose from Day 1 to Week 12 | 12 weeks | 
| Proportion of Subjects Achieving HbA1c Goal of <7.0% | Percent of subjects who achieved HbA1c of <7% at Week 12 | 12 weeks | 
| Proportion of Subjects Achieving HbA1c Goal of <6.5% | Percent of subjects who achieved HbA1c of <6% at Week 12 | 12 weeks | 
| Change in Waist Circumference From Baseline | Change in waist circumference from Day 1 to Week 12 | 12 weeks | 
| Change of Postprandial (2 Hours After Dinner) Blood Glucose Level From Baseline | Change in postprandial (2 hours after dinner) blood glucose levels from Day 1 to Week 12 | 12 weeks | 
| Change of Oral Glucose Tolerance Test From Baseline | Change in oral glucose tolerance test results from Day 1 to Week 12 | 12 weeks | 
| Change of Score in Audit of Diabetes-Dependent Quality of Life Questionnaire From Baseline | Individual 19 domains were calculated as a weighted score (WS) for each domain. Average weighted impact score = summing of WS for each domain/19 domains. Total range possible is -9 to 3, and higher number means improvement in quality of life. | 12 weeks |