Clinical trial NCT01969994: Absorption, Metabolism, and Excretion of (-)-[2-14C]Epicatechin in Humans
Official title: A Single-Center, Open-Label Study to Evaluate the Absorption, Metabolism, and Excretion of (-)-[2-14C]Epicatechin Following Oral Intake
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: ADME
Keywords: Epicatechin
Flavanols
Procyanidins
Polyphenols
Phytonutrients
AMDE
Antioxidants
Lead sponsor: The Institutes for Pharmaceutical Discovery, LLC
Sponsor class: INDUSTRY
Collaborators: name: Covance
name: Mars, Inc.
First posted: 2013-10-25
Enrollment: 12
Sex: MALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP

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.

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.

Eligibility criteria: 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;

Primary outcomes:
measure: Change in levels of (-)-[2-14C]epicatechin-derived radioactivity in blood, plasma, urine, and feces;
timeFrame: 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:
measure: Composite of pharmacokinetic (PK) parameters of total (-)-[2-14C]epicatechin-derived radioactivity levels in plasma, urine and feces.
timeFrame: 0 (prior to the ingestion of (-)-[2-14C]epicatechin) up to 240 h or untill volunteers meet discharge criteria
measure: Composite of pharmacokinetic (PK) parameters of individual (-)-[2-14C]epicatechin metabolites in plasma and urine
timeFrame: 0 (prior to the ingestion of (-)-[2-14C]epicatechin) up to 240 h or untill volunteers meet discharge criteria
Other outcomes:
Locations:
city: Madison
country: United States
facility: Covance Clinical Pharmacology Inc.
state: Wisconsin
Study officials:
affiliation: Covance Clinical Pharmacology Inc.
name: Christine L Hale, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: IPD, LLC
name: Michael Fare
role: STUDY_DIRECTOR
affiliation: Mars, Inc.
name: Javier I Ottaviani, Ph.D.
role: STUDY_DIRECTOR
References:
citation: 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.