Early Phase Pre-Clinical and Initial Clinical Research on Epicatechin

Study Overview
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Brief Summary
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Early Phase Pre-Clinical and Initial Clinical Research on (+)- Epicatechin.

Detailed Description
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This project is a double-blinded randomized Phase I study that will include dose-ranging one day PK and pharmacodynamic (PD) studies. Subjects will include healthy individuals and subjects who meet the American Diabetes Association (ADA) criteria for pre-diabetes, including IFG.

Official Title
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(+)-Epicatechin: Early Phase Pre-Clinical and Initial Clinical Research on Epicatechin

Conditions
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Pre-diabetes

Intervention / Treatment
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* Drug: (+)-Epicatechin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy or pre-diabetic based on medical history 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 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 Body Mass Index (BMI) > 27 kg/m^2 Definition of pre-diabetes: impaired fasting glucose (IFG, fasting glucose = 100-125 mg/dL) and 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 ULN), determined in the last 6 months by a certified clinical laboratory Recent MI 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

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 10 mg (+)-epicatechin<br>4 subjects randomized to one dose of 10 mg (+)-epicatechin taken orally | Drug: (+)-Epicatechin<br>* The drug to be tested is (+)-epicatechin, synthesized under GMP standards. Subjects will be given a single oral dose of (+)- epicatechin and followed on an inpatient basis over 24 hours. Three (3) different dose levels will be tested in a randomized, double-blind design: (+)- epicatechin 10 mg, 30 mg, or 100 mg. As this is a pilot study, a placebo arm will not be included.<br>* Other names: Epicatechin;|
| Experimental: 30 mg (+)-epicatechin<br>4 subjects randomized to one dose of 30 mg (+)-epicatechin taken orally | Drug: (+)-Epicatechin<br>* The drug to be tested is (+)-epicatechin, synthesized under GMP standards. Subjects will be given a single oral dose of (+)- epicatechin and followed on an inpatient basis over 24 hours. Three (3) different dose levels will be tested in a randomized, double-blind design: (+)- epicatechin 10 mg, 30 mg, or 100 mg. As this is a pilot study, a placebo arm will not be included.<br>* Other names: Epicatechin;|
| Experimental: 100 mg (+)-epicatechin<br>4 subjects randomized to one dose of 100 mg (+)-epicatechin taken orally | Drug: (+)-Epicatechin<br>* The drug to be tested is (+)-epicatechin, synthesized under GMP standards. Subjects will be given a single oral dose of (+)- epicatechin and followed on an inpatient basis over 24 hours. Three (3) different dose levels will be tested in a randomized, double-blind design: (+)- epicatechin 10 mg, 30 mg, or 100 mg. As this is a pilot study, a placebo arm will not be included.<br>* Other names: Epicatechin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Circulating Urinary Concentrations of Intact Epicatechin and Epi Metabolites | This will be initial PK study on synthetic (+)-epicatechin in humans. Circulating and urinary concentrations of intact epicatechin and epicatechin metabolites, including specific enantiomers | Baseline and 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Major Safety Endpoints | Clinically significant differences in the major safety endpoints are defined as: BP (10 mm Hg change), HR (10 bpm), creatinine (>1.5 ULN), and highly conservative changes in alkaline phosphatase and liver transaminases (>1.5 ULN). | Baseline and 24 hours | 
| Change From Baseline in Circulating Glucose Concentrations (mg/dL*24hr) |  | Baseline and 24 hours | 
| Change From Baseline in Circulating Insulin Concentrations (uU/mL*24hr) |  | Baseline and 24 hours | 
| Change From Baseline in Circulating C-Peptide Concentrations (ng/mL*24hr) |  | Baseline and 24 hours |