Safety and Pharmacokinetics of an Extract of Naringenin

Early Phase 1

Completed

Conditions: Pharmacokinetics
Safety Issues

Interventions: Dietary Supplement: Naringenin
Other: Placebo

Registration Number: NCT03582553

Lead Sponsor: Pennington Biomedical Research Center

Brief Summary: This study evaluates the safety of administering single ascending doses (150, 300, 600, and 900 mg) of a citrus extract of the flavonoid narigenin, and assesses the blood concentrations of naringenin following oral administration of the extract.

Detailed Description: Naringenin is a component of food with therapeutic potential to improve glucose metabolism. In order to explore the mechanisms by which naringenin may increase energy expenditure and improve glucose metabolism in humans, it is of vital importance that the safety, tolerability, and bioavailability of naringenin are evaluated, when administered to humans. This study tests the safety of four doses of a citrus extract of naringenin and measures serum concentrations of naringenin at the 150 mg and 600 mg doses over a period of 24 hours, and at the 300 and 900 mg doses at four hours after subjects have been given the respective doses of naringenin.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 18

Inclusion Criteria

Adult (≥18 years)
Body mass index between 20 and 35 kg/m2
Must have fasting blood sugar <126 mg/dL)
Must be willing to refrain from consuming citrus fruits and tomato in any form, for 36 hours prior to each test day.

Exclusion Criteria

Report citrus allergies.
Report a history of cardiovascular disease, diabetes, or cancer
Have evidence of hepatic disease or dysfunction
Are currently pregnant or breastfeeding
Are women of childbearing potential who will not use an effective method of birth control
Chronically use of medications except over the counter medications that have been stopped 72 hours prior to the study visit
Report clinically significant GI malabsorption syndromes
Have clinically significant abnormal laboratory markers
Anticipate surgery during the study period.
Report history of substance abuse or alcoholism or significant psychiatric disorder that would interfere with the ability to complete the study.
Have donated blood during the month prior to study entry or plan to do so during the study.
Have participated in other studies using an investigational drug during the preceding three months.
Are current smokers or have smoked within the previous three months.

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
600 mg dose	Naringenin	Blood will be drawn at at 0, 2, 3, 3.5, 4, 4.5, 6, 8,12, and 24 hours to measure serum naringenin concentrations in response to a single 600 mg oral dose of an extract of Citrus sinensis (sweet orange) containing naringenin and its precursor naringin.
900 mg dose	Naringenin	Blood will be drawn at at 0, and 4 hours to measure serum naringenin concentrations in response to a single 900 mg oral dose of an extract of Citrus sinensis (sweet orange) containing naringenin and its precursor naringin.
Placebo	Placebo	Subjects in the first cohort will receive 150 mg and 300 mg ascending doses of naringenin and subjects in the second cohort will receive 600 mg and 900 mg ascending doses of naringenin. Each cohort will also have a placebo group.
150 mg dose	Naringenin	Blood will be drawn at at 0, 2, 3, 3.5, 4, 4.5, 6, 8,12, and 24 hours to measure serum naringenin concentrations in response to a single 150 mg oral dose of an extract of Citrus sinensis (sweet orange) containing naringenin and its precursor naringin.
300 mg dose	Naringenin	Blood will be drawn at at 0, and 4 hours to measure serum naringenin concentrations in response to a single 300 mg oral dose of an extract of Citrus sinensis (sweet orange) containing naringenin and its precursor naringin.

Primary Outcome Measures

Name	Time	Method
Incidence of Treatment-emergent Adverse Events Following a Single Dose of a Citrus Extract of Naringenin	Adverse events were collected over approximately five weeks which included three study days and two washout periods of at least one week.	All adverse events will be recorded following the first administration of the study product or placebo. The study physician in consultation with the coordinator will review and determine whether a subject can be administered the next ascending dose. The cohorts will be run in series. There will be an interval of up to four weeks between the two cohorts. During this time an interim analysis will be conducted and a safety summary of adverse events for Cohort 1 will be compiled and reviewed by the investigators. Dose safety will be investigated by compiling by treatment (e.g. 150 mg dose, 300 mg dose, placebo) a list of adverse events. The frequency of these events will be counted and compared with the placebo group.

Secondary Outcome Measures

Name	Time	Method
Measurement of Area Under the Serum Naringenin Concentration Versus Time Curve at 150 and 600 mg Doses	0, 2, 3, 3.5, 4, 4.5, 6, 8,12, and 24 hours	Blood will be drawn over a period of 24 hours following ingestion of the 150 and 600mg doses of naringenin and serum concentrations will be measured. The area under the serum concentration versus time curve will be determined.
Measurement of Time to Peak Concentration of Serum Naringenin at 150 and 600 mg Doses	24 hours	Blood will be drawn over a period of 24 hours following ingestion of the 150 and 600mg doses of naringenin and serum naringenin concentrations will be measured. The time to peak serum naringenin concentration will be determined.
Measurement of Maximal Concentration of Serum Naringenin at 150 and 600 mg Doses	0, 2, 3, 3.5, 4, 4.5, 6, 8,12, and 24 hours	Blood will be drawn over a period of 24 hours following ingestion of the 150 and 600mg doses of naringenin and serum concentrations will be measured. The maximal serum concentration will be determined.
Measurement of Apparent Oral Clearance of Naringenin at 150 and 600 mg Doses	0, 2, 3, 3.5, 4, 4.5, 6, 8,12, and 24 hours	Blood will be drawn over a period of 24 hours following ingestion of the 150 and 600mg doses of naringenin and serum naringenin concentrations will be measured. The apparent oral clearance of naringenin will be determined.
Measurement of Half Life of Naringenin at 150 and 600 mg Doses	0, 2, 3, 3.5, 4, 4.5, 6, 8,12, and 24 hours	Blood will be drawn over a period of 24 hours following ingestion of the 150 and 600mg doses of naringenin and serum naringenin concentrations will be measured. The half life of naringenin will be determined.
Measurement of Four-hour Concentration of Serum Naringenin at 300 and 900 mg Doses	0 and 4 hours	Blood will be drawn at 0 hours and 4 hours following ingestion of the 300 and 900mg doses of naringenin and serum naringenin concentrations will be measured.