Absorption, Metabolism, and Excretion of (-)-[2-14C]Epicatechin in Humans

October 22, 2013 updated by: The Institutes for Pharmaceutical Discovery, LLC

A Single-Center, Open-Label Study to Evaluate the Absorption, Metabolism, and Excretion of (-)-[2-14C]Epicatechin Following Oral Intake

The purpose of this study is to determine the absorption, metabolism and excretion of (-)-epicatechin using the radiolabeled tracer (-)-[2-14C]epicatechin in healthy male volunteers observing a flavanol-/procyanidin-controlled background diet.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Flavanols and their oligomeric derivatives, the procyanidins, are plant-derived compounds commonly present in the human diet. Accumulating data demonstrate a causal role for dietary flavanols in mediating the cardiovascular benefits associated with the consumption of flavanol-/procyanidin-containing foods. In this context, there exists a great interest in understanding the absorption, distribution, metabolism and excretion (ADME) of flavanols in humans. While significant advances in understanding the ADME of flavanols were made, the data obtained thus far remain fairly preliminary and with significant shortfalls and seeming contradictions. Aimed at addressing the challenges and gaps of previous investigations, this study will investigate the ADME of (-)-epicatechin, one of the most abundant dietary flavanols, following the intake of radiolabeled (-)-[2-14C]epicatechin by healthy humans observing a flavanol-/procyanidin-controlled background diet.

Study Type

Interventional

Enrollment (Actual)

12

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Wisconsin
      • Madison, Wisconsin, United States, 53704
        • Covance Clinical Pharmacology Inc.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 50 years (ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Male

Description

Inclusion Criteria1.

  1. males, in good health, between 18 and 50 years of age and between 60 and 100 kg;
  2. body mass index (BMI) between 19 and 30 kg/m2.
  3. clinical laboratory evaluations (including clinical chemistry [fasted at least 10 hours], hematology, and urinalysis) within the reference range for the testing laboratory, unless deemed not clinically significant by the Investigator;
  4. negative hepatitis panel (including hepatitis B surface antigen [HbsAg] and hepatitis C virus antibody [anti-HCV]) and human immunodeficiency virus (HIV) antibody screens;
  5. a minimum of 1 bowel movement per day.

Exclusion Criteria:

  1. history or clinical manifestations of significant metabolic, hematological, pulmonary, cardiovascular, gastrointestinal, neurologic, hepatic, renal, urological, or psychiatric disorders;
  2. allergies to peanuts, nuts, or other foods;
  3. lactose intolerance;
  4. history of stomach or intestinal surgery, except that appendectomy or hernia were allowed;
  5. history of alcoholism or drug addiction within 1 year prior to study entry (ie, at Screening);
  6. use of any tobacco products (including cigarette, pipe, cigar, chewing, nicotine patch, or nicotine gum) within 6 months prior to study entry;
  7. use of any agents (excluding those provided as part of this study procedure) affecting the liver enzymes;
  8. use of aspirin-containing drugs and any other over-the-counter, non-prescription preparations (including vitamins, minerals, and phytotherapeutic/herbal/plant-derived preparations) during the study, unless deemed acceptable by the Investigator;
  9. use of any alcohol-containing or caffeine-containing products/medications within 72 hours prior to (-)-[2-14C]epicatechin ingestion;
  10. regular consumption of more than 2 alcoholic drinks per day;
  11. vegans, vegetarians and/or anyone who consumed less than 1 to 2 servings of fruits and or vegetables per day;
  12. participation in more than one other radiolabeled investigational study drug trial within 12 months prior to study entry or exposure to significant radiation within 12 months prior to study entry;

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Controlled dietary background & (-)-[2-14C]epicatechin intake
Other: Controlled dietary background
Controlled dietary flavanol-/procyanidin- background, consisting of daily intake for 14 days (day -17 to -4) of a commercially available flavanol-/procyanidin-containing cocoa-based drink (250 mg cocoa flavanols; 40 mg of (-)-epicatechin) followed by a 4-day period (day -4 to 0) of a low-flavanol diet.
Other: (-)-[2-14C]epicatechin intake
Single oral intake of an aqueous solution of a mixture of non-radiolabeled (-)-epicatechin and a single-carbon-14 radiolabeled (-)-[2-14C]epicatechin. The target amount of EC delivered with test drink will be 60 mg, 58.5 mg of which consist of non-radiolabled EC and 1.54 mg (300 µCi) consist of (-)-[2-14C]epicatechin.
Other Names:
  • (-)-cis-3,3',4',5,7-Pentahydroxyflavane
  • (2R,3R) - 2- (3,4- Dihydroxyphenyl) - 3,4- dihydro- 1(2H) - benzopyran- 3,5,7- triol

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Change in levels of (-)-[2-14C]epicatechin-derived radioactivity in blood, plasma, urine, and feces;
Time Frame: 0 (prior to the ingestion of (-)-[2-14C]epicatechin), 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours postdose, and at every subsequent 24 hour timepoint up to 240 h or until volunteers meet discharge criteria
0 (prior to the ingestion of (-)-[2-14C]epicatechin), 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours postdose, and at every subsequent 24 hour timepoint up to 240 h or until volunteers meet discharge criteria

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Composite of pharmacokinetic (PK) parameters of total (-)-[2-14C]epicatechin-derived radioactivity levels in plasma, urine and feces.
Time Frame: 0 (prior to the ingestion of (-)-[2-14C]epicatechin) up to 240 h or untill volunteers meet discharge criteria
PK parameters: Cmax: maximum observed concentration in plasma; tmax: time to maximum concentration in plasma; AUC0-t: area under the plasma radioactivity-time curve from hour 0 to the last measurable concentration in plasma; AUC0-∞: area under the plasma concentration-time curve extrapolated to infinity; λZ: apparent terminal elimination rate constant in plasma; t1/2: apparent terminal elimination half-life in plasma; CL/F: systemic clearance; Vd/F: apparent volume of distribution; CLR: renal clearance; Aeu(0-t): cumulative amount excreted in the urine over each sampling interval and the total interval examined; Aef(0-t): Cumulative amount excreted in the feces over each sampling interval and the total interval examined.
0 (prior to the ingestion of (-)-[2-14C]epicatechin) up to 240 h or untill volunteers meet discharge criteria
Composite of pharmacokinetic (PK) parameters of individual (-)-[2-14C]epicatechin metabolites in plasma and urine
Time Frame: 0 (prior to the ingestion of (-)-[2-14C]epicatechin) up to 240 h or untill volunteers meet discharge criteria

PK parameters of each (-)-epicatechin metabolite:

Cmax: maximum observed concentration in plasma; tmax: time to maximum concentration in plasma; AUC0-t: area under the plasma concentration-time curve from hour 0 to the last measurable concentration in plasma; AUC0-∞: area under the plasma concentration-time curve extrapolated to infinity; λZ: apparent terminal elimination rate constant in plasma; t1/2: apparent terminal elimination half-life in plasma; CL/F: systemic clearance; Vd/F apparent volume of distribution; CLR: renal clearance; Aeu(0-t): cumulative amount excreted in the urine over each sampling interval and the total interval examined.
0 (prior to the ingestion of (-)-[2-14C]epicatechin) up to 240 h or untill volunteers meet discharge criteria

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The Institutes for Pharmaceutical Discovery, LLC

Collaborators

Covance
Mars, Inc.

Investigators

  • Principal Investigator: Christine L Hale, MD, Covance Clinical Pharmacology Inc.
  • Study Director: Michael Fare, IPD, LLC
  • Study Director: Javier I Ottaviani, Ph.D., Mars, Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2009

Primary Completion (Actual)

December 1, 2009

Study Completion (Actual)

December 1, 2009

Study Registration Dates

First Submitted

October 22, 2013

First Submitted That Met QC Criteria

October 22, 2013

First Posted (Estimate)

October 25, 2013

Study Record Updates

Last Update Posted (Estimate)

October 25, 2013

Last Update Submitted That Met QC Criteria

October 22, 2013

Last Verified

October 1, 2013

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • 8215022

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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