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

NCT01969994 | Completed DMC

• 1 other identifier: 8215022
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

ADME

Keywords

Epicatechin; Flavanols; Procyanidins; Polyphenols; Phytonutrients; AMDE; Antioxidants

Outcome Measures

Primary Outcomes (1)

• Change in levels of (-)-[2-14C]epicatechin-derived radioactivity in blood, plasma, urine, and feces;

  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 Outcomes (2)

• Composite of pharmacokinetic (PK) parameters of total (-)-[2-14C]epicatechin-derived radioactivity levels in plasma, urine and feces.

  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

  0 (prior to the ingestion of (-)-[2-14C]epicatechin) up to 240 h or untill volunteers meet discharge criteria

Study Arms (1)

Controlled dietary background & (-)-[2-14C]epicatechin intake

EXPERIMENTAL

Other: Controlled dietary background; Other: (-)-[2-14C]epicatechin intake

Interventions

Controlled dietary background OTHER

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.

Controlled dietary background & (-)-[2-14C]epicatechin intake

(-)-[2-14C]epicatechin intake OTHER

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.

Also known as: (-)-cis-3,3',4',5,7-Pentahydroxyflavane, (2R,3R) - 2- (3,4- Dihydroxyphenyl) - 3,4- dihydro- 1(2H) - benzopyran- 3,5,7- triol

Controlled dietary background & (-)-[2-14C]epicatechin intake

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• males, in good health, between 18 and 50 years of age and between 60 and 100 kg;
• body mass index (BMI) between 19 and 30 kg/m2.
• 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;
• negative hepatitis panel (including hepatitis B surface antigen \[HbsAg\] and hepatitis C virus antibody \[anti-HCV\]) and human immunodeficiency virus (HIV) antibody screens;
• a minimum of 1 bowel movement per day.

You may not qualify if:

• history or clinical manifestations of significant metabolic, hematological, pulmonary, cardiovascular, gastrointestinal, neurologic, hepatic, renal, urological, or psychiatric disorders;
• allergies to peanuts, nuts, or other foods;
• lactose intolerance;
• history of stomach or intestinal surgery, except that appendectomy or hernia were allowed;
• history of alcoholism or drug addiction within 1 year prior to study entry (ie, at Screening);
• use of any tobacco products (including cigarette, pipe, cigar, chewing, nicotine patch, or nicotine gum) within 6 months prior to study entry;
• use of any agents (excluding those provided as part of this study procedure) affecting the liver enzymes;
• 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;
• use of any alcohol-containing or caffeine-containing products/medications within 72 hours prior to (-)-\[2-14C\]epicatechin ingestion;
• regular consumption of more than 2 alcoholic drinks per day;
• vegans, vegetarians and/or anyone who consumed less than 1 to 2 servings of fruits and or vegetables per day;
• 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;

Sponsors & Collaborators

• The Institutes for Pharmaceutical Discovery, LLC: lead
• Covance: collaborator
• Mars, Inc.: collaborator

Study Sites (1)

Covance Clinical Pharmacology Inc.

Madison, Wisconsin, 53704, United States

Location

Related Publications (1)

• Ottaviani JI, Borges G, Momma TY, Spencer JP, Keen CL, Crozier A, Schroeter H. The metabolome of [2-(14)C](-)-epicatechin in humans: implications for the assessment of efficacy, safety, and mechanisms of action of polyphenolic bioactives. Sci Rep. 2016 Jul 1;6:29034. doi: 10.1038/srep29034.

  PMID: 27363516 DERIVED

Study Officials

• Christine L Hale, MD

  Covance Clinical Pharmacology Inc.

  PRINCIPAL INVESTIGATOR

• Michael Fare

  IPD, LLC

  STUDY DIRECTOR

• Javier I Ottaviani, Ph.D.

  Mars, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 22, 2013
• First Posted: October 25, 2013
• Study Start: December 1, 2009
• Primary Completion: December 1, 2009
• Study Completion: December 1, 2009
• Last Updated: October 25, 2013

Record last verified: 2013-10

Locations

US (1)