Early Phase Pre-Clinical and Initial Clinical Research on Epicatechin (Part 2)

This project is a double-blinded, placebo-controlled, randomized, Phase I study that will
include (+)-epicatechin dosing over seven days.

- Subjects will meet the American Diabetes Association (ADA) criteria for pre-diabetes,
including impaired fasting glucose (IFG) [refer to inclusion/exclusion criteria].

- The Project includes: 7 day evaluation of a single daily dose of synthetic
(+)-epicatechin in pre-diabetic individuals as compared to placebo.

- The Project has 4 outpatient clinic study visits: screening (Visit 1), randomization
(Visit 2), end of study drug (Visit 3), follow up end of study (Visit 4).

- This Project has 2 telephone visits

Primary hypothesis: As these studies are designed to evaluate safety and tolerability, there
is no primary hypothesis to test.

Primary outcome measures. Vital signs and safety labs: BP, HR, creatinine, alkaline
phosphatase, and liver transaminases

These studies will provide initial data about if (+)-epicatechin can influence glycemic
control in individuals with prediabetes.

Inclusion Criteria:

- Pre-diabetic based on medical history and screening results

- Male or female

- Must be 21 to 75 years of age (inclusive)

- Able to give informed consent to the procedures

- If female, must be either postmenopausal or test negative for pregnancy at screening
and on the day of the procedure. Women on estrogen therapy will be included.

- If female of childbearing potential, must practice and be willing to continue to
practice appropriate birth control during the entire duration of the study

- Medication use stable for 4 weeks prior to screening

- Body Mass Index (BMI) > 27 kg/m2

- Definition of pre-diabetes: impaired fasting glucose (IFG, fasting glucose = 100-125
mg/dL) and/OR elevated HbA1c (5.7-6.4%), each in the absence of other risk factors
for diabetes

Exclusion Criteria:

- Type 2 diabetes

- Pregnancy

- Younger than 21 or older than 75 years of age

- Clinically significant abnormalities in liver or kidney function (>3x upper limit of
normal (ULN)), determined in the last 6 months by a certified clinical laboratory

- Recent myocardial infarct or stroke (within 6 months of screening)

- Blood pressure (BP) >160 mmHg Systolic and >100 mmHg Diastolic

- Medications - thiazolidinediones, any steroids, anti-depressants, weight loss drugs

- Other diseases, besides type 2 diabetes, influencing carbohydrate metabolism