Diabetes Mellitus Type 2 in Obese
Conditions
Brief summary
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).
Interventions
DRUGCyclo-Z
DRUGPlacebo
Sponsors
NovMetaPharma Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change of HbA1c Level From Baseline | 12 weeks | Change in HbA1c from Day 1 to Week 12 |
| Change of Body Weight From Baseline | 12 weeks | Change in body weight from Day 1 to Week 12 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Subjects Achieving HbA1c Goal of <6.5% | 12 weeks | Percent of subjects who achieved HbA1c of \<6% at Week 12 |
| Change in Waist Circumference From Baseline | 12 weeks | Change in waist circumference from Day 1 to Week 12 |
| Change of Fasting Plasma Glucose Level From Baseline | 12 weeks | Change in fasting plasma glucose from Day 1 to Week 12 |
| Change of Oral Glucose Tolerance Test From Baseline | 12 weeks | Change in oral glucose tolerance test results from Day 1 to Week 12 |
| Change of Score in Audit of Diabetes-Dependent Quality of Life Questionnaire From Baseline | 12 weeks | 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. |
| Change of Postprandial (2 Hours After Dinner) Blood Glucose Level From Baseline | 12 weeks | Change in postprandial (2 hours after dinner) blood glucose levels from Day 1 to Week 12 |
| Proportion of Subjects Achieving HbA1c Goal of <7.0% | 12 weeks | Percent of subjects who achieved HbA1c of \<7% at Week 12 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 3 mg CHP Plus 23 mg Zinc Cyclo-Z containing 23 mg zinc plus 3 mg CHP
Cyclo-Z | 16 |
| 9 mg CHP Plus 23 mg Zinc Cyclo-Z containing 23 mg zinc plus 9 mg CHP
Cyclo-Z | 16 |
| 15 mg CHP Plus 23 mg Zinc Cyclo-Z containing 23 mg zinc plus 15 mg CHP
Cyclo-Z | 17 |
| Placebo Placebo
Placebo | 15 |
| Total | 64 |
Baseline characteristics
| Characteristic | 3 mg CHP Plus 23 mg Zinc | 9 mg CHP Plus 23 mg Zinc | 15 mg CHP Plus 23 mg Zinc | Placebo | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 5 Participants | 2 Participants | 1 Participants | 10 Participants |
| Age, Categorical Between 18 and 65 years | 14 Participants | 11 Participants | 15 Participants | 14 Participants | 54 Participants |
| Age, Continuous | 56.9 years STANDARD_DEVIATION 7.58 | 59.9 years STANDARD_DEVIATION 9.89 | 55.2 years STANDARD_DEVIATION 10.9 | 57.1 years STANDARD_DEVIATION 5.53 | 57.3 years STANDARD_DEVIATION 8.77 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants | 9 Participants | 4 Participants | 5 Participants | 24 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants | 7 Participants | 13 Participants | 9 Participants | 39 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Region of Enrollment United States | 16 participants | 16 participants | 17 participants | 15 participants | 64 participants |
| Sex: Female, Male Female | 5 Participants | 7 Participants | 8 Participants | 8 Participants | 28 Participants |
| Sex: Female, Male Male | 11 Participants | 9 Participants | 9 Participants | 7 Participants | 36 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 15 | 0 / 16 | 0 / 16 | 0 / 14 |
| other Total, other adverse events | 5 / 15 | 7 / 16 | 13 / 16 | 7 / 14 |
| serious Total, serious adverse events | 1 / 15 | 0 / 16 | 0 / 16 | 0 / 14 |
Outcome results
Primary
Change of Body Weight From Baseline
Change in body weight from Day 1 to Week 12
Time frame: 12 weeks
Population: Efficacy Analysis Set (N=61) was used for the efficacy analysis. However, only 54 subjects had Week 12 values for weight (12, 15, 14, and 13, respectively).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 3 mg CHP Plus 23 mg Zinc | Change of Body Weight From Baseline | -0.73 kg | Standard Deviation 1.524 |
| 9 mg CHP Plus 23 mg Zinc | Change of Body Weight From Baseline | 0.61 kg | Standard Deviation 3.4 |
| 15 mg CHP Plus 23 mg Zinc | Change of Body Weight From Baseline | -0.92 kg | Standard Deviation 2.381 |
| Placebo | Change of Body Weight From Baseline | 2.38 kg | Standard Deviation 5.702 |
Primary
Change of HbA1c Level From Baseline
Change in HbA1c from Day 1 to Week 12
Time frame: 12 weeks
Population: Efficacy Analysis Set (N=61) was used for the efficacy analysis. However only 54 subjects had Week 12 values (12, 15, 14, and 13 subjects, respectively).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 3 mg CHP Plus 23 mg Zinc | Change of HbA1c Level From Baseline | -0.21 (%) | Standard Deviation 0.979 |
| 9 mg CHP Plus 23 mg Zinc | Change of HbA1c Level From Baseline | -0.17 (%) | Standard Deviation 1.038 |
| 15 mg CHP Plus 23 mg Zinc | Change of HbA1c Level From Baseline | -0.43 (%) | Standard Deviation 1.132 |
| Placebo | Change of HbA1c Level From Baseline | -0.04 (%) | Standard Deviation 1.068 |
Secondary
Change in Waist Circumference From Baseline
Change in waist circumference from Day 1 to Week 12
Time frame: 12 weeks
Population: Efficacy Analysis Set (N=61) was used for the efficacy analysis. However, only 53 subjects had Week 12 values (12, 14, 14, and 13 respectively).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 3 mg CHP Plus 23 mg Zinc | Change in Waist Circumference From Baseline | -0.71 cm | Standard Deviation 6.881 |
| 9 mg CHP Plus 23 mg Zinc | Change in Waist Circumference From Baseline | -1.31 cm | Standard Deviation 4.099 |
| 15 mg CHP Plus 23 mg Zinc | Change in Waist Circumference From Baseline | -0.70 cm | Standard Deviation 8.812 |
| Placebo | Change in Waist Circumference From Baseline | -0.79 cm | Standard Deviation 5.144 |
Secondary
Change of Fasting Plasma Glucose Level From Baseline
Change in fasting plasma glucose from Day 1 to Week 12
Time frame: 12 weeks
Population: Efficacy Analysis Set (N=61) was used for the efficacy analysis. However, only 54 subjects had Week 12 values (12, 15, 14, and 13, respectively).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 3 mg CHP Plus 23 mg Zinc | Change of Fasting Plasma Glucose Level From Baseline | -10.4 mg/dL | Standard Deviation 59.2 |
| 9 mg CHP Plus 23 mg Zinc | Change of Fasting Plasma Glucose Level From Baseline | 25.4 mg/dL | Standard Deviation 65.66 |
| 15 mg CHP Plus 23 mg Zinc | Change of Fasting Plasma Glucose Level From Baseline | 5.3 mg/dL | Standard Deviation 49.24 |
| Placebo | Change of Fasting Plasma Glucose Level From Baseline | -23.4 mg/dL | Standard Deviation 95.78 |
Secondary
Change of Oral Glucose Tolerance Test From Baseline
Change in oral glucose tolerance test results from Day 1 to Week 12
Time frame: 12 weeks
Population: Efficacy Analysis Set (N=61) was used for the efficacy analysis. However, only 53 subjects had Week 12 oral glucose tolerance test results (12, 15, 14, and 12, respectively).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 3 mg CHP Plus 23 mg Zinc | Change of Oral Glucose Tolerance Test From Baseline | -13.8 mg/dL | Standard Deviation 51.16 |
| 9 mg CHP Plus 23 mg Zinc | Change of Oral Glucose Tolerance Test From Baseline | 28.4 mg/dL | Standard Deviation 89.45 |
| 15 mg CHP Plus 23 mg Zinc | Change of Oral Glucose Tolerance Test From Baseline | -19.6 mg/dL | Standard Deviation 85.62 |
| Placebo | Change of Oral Glucose Tolerance Test From Baseline | -33.6 mg/dL | Standard Deviation 75.72 |
Secondary
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
Time frame: 12 weeks
Population: Efficacy Analysis Set (N=61) was used for the efficacy analysis. However, only 51 subjects had Week 12 postprandial glucose values (11, 14, 14, and 12, respectively).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 3 mg CHP Plus 23 mg Zinc | Change of Postprandial (2 Hours After Dinner) Blood Glucose Level From Baseline | -14.56 mg/dL | Standard Deviation 40.21 |
| 9 mg CHP Plus 23 mg Zinc | Change of Postprandial (2 Hours After Dinner) Blood Glucose Level From Baseline | 8.78 mg/dL | Standard Deviation 38.543 |
| 15 mg CHP Plus 23 mg Zinc | Change of Postprandial (2 Hours After Dinner) Blood Glucose Level From Baseline | -5.25 mg/dL | Standard Deviation 62.754 |
| Placebo | Change of Postprandial (2 Hours After Dinner) Blood Glucose Level From Baseline | -13.95 mg/dL | Standard Deviation 54.262 |
Secondary
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.
Time frame: 12 weeks
Population: Efficacy Analysis Set (N=61) was used for the efficacy analysis. However, only 51 subjects had Week 12 ADDQoL results (9, 15, 14, and 13, respectively).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 3 mg CHP Plus 23 mg Zinc | Change of Score in Audit of Diabetes-Dependent Quality of Life Questionnaire From Baseline | -0.23 Score on a scale | Standard Deviation 2.311 |
| 9 mg CHP Plus 23 mg Zinc | Change of Score in Audit of Diabetes-Dependent Quality of Life Questionnaire From Baseline | 0.21 Score on a scale | Standard Deviation 2.171 |
| 15 mg CHP Plus 23 mg Zinc | Change of Score in Audit of Diabetes-Dependent Quality of Life Questionnaire From Baseline | 0.35 Score on a scale | Standard Deviation 1.075 |
| Placebo | Change of Score in Audit of Diabetes-Dependent Quality of Life Questionnaire From Baseline | 1.53 Score on a scale | Standard Deviation 2.655 |
Secondary
Proportion of Subjects Achieving HbA1c Goal of <6.5%
Percent of subjects who achieved HbA1c of \<6% at Week 12
Time frame: 12 weeks
Population: Efficacy Analysis Set (N=61) was used for the efficacy analysis. However, only 54 subjects had Week 12 values (12, 15, 14, and 13, respectively).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 3 mg CHP Plus 23 mg Zinc | Proportion of Subjects Achieving HbA1c Goal of <6.5% | 0 Participants |
| 9 mg CHP Plus 23 mg Zinc | Proportion of Subjects Achieving HbA1c Goal of <6.5% | 0 Participants |
| 15 mg CHP Plus 23 mg Zinc | Proportion of Subjects Achieving HbA1c Goal of <6.5% | 1 Participants |
| Placebo | Proportion of Subjects Achieving HbA1c Goal of <6.5% | 1 Participants |
Secondary
Proportion of Subjects Achieving HbA1c Goal of <7.0%
Percent of subjects who achieved HbA1c of \<7% at Week 12
Time frame: 12 weeks
Population: Efficacy Analysis Set (N=61) was used for the efficacy analysis. However, only 54 subjects had Week 12 values (12, 15, 14, and 13 respectively).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 3 mg CHP Plus 23 mg Zinc | Proportion of Subjects Achieving HbA1c Goal of <7.0% | 4 Participants |
| 9 mg CHP Plus 23 mg Zinc | Proportion of Subjects Achieving HbA1c Goal of <7.0% | 3 Participants |
| 15 mg CHP Plus 23 mg Zinc | Proportion of Subjects Achieving HbA1c Goal of <7.0% | 2 Participants |
| Placebo | Proportion of Subjects Achieving HbA1c Goal of <7.0% | 2 Participants |