Pharmacokinetic Study in Healthy Volunteers
Conditions
Brief summary
This study investigates the differences in the kinetic parameters of fisetin in two cohorts of healthy volunteers: Cohort 1) volunteers aged 18-30 years (n = 40) Cohort 2) volunteers aged 65 years or older (n = 40) The purpose of this study is: 1. To describe the fisetin kinetics after a single dose oral administration in older age. 2. To compare the fisetin kinetics after a single dose oral administration in old and young age. FISEKIN-1 is designed as a four-arm study protocol. As well as two different age groups (18-30 years vs. 65 years and older), we want to compare fisetin kinetic parameters in fasted and fed condition: Arm 1) 500 mg fisetin (1x 5 capsule), fasted condition, cohort 1: young age Arm 2) 500 mg fisetin (1x 5 capsule), fasted condition, cohort 2: old age Arm 3) 500 mg fisetin (1x 5 capsule), fed condition, cohort 1: young age Arm 4) 500 mg fisetin (1x 5 capsule), fed condition, cohort 2: old age
Detailed description
The study is designed as an open-label, two-cohorts (young vs. old), four-arm, cross-over, single oral dose protocol. A single oral dose of fisetin will be administered as capsules with 240 ml of still water in the overnight fasting condition (arm 1; 2) or in fed condition (arm 3; 4). The arms will be conducted in each participant in random order with a wash-out period of at least one week between each arm. Fed condition (arm 3; 4): We will serve a high-caloric and high-fat meal based on the recommendation of the FDA (Food and Drug Administration) for food-effect studies. This meal will contain two slices of toast with butter, two eggs fried in butter, approx. 113 g hash brown potatoes and 240 ml whole milk. A total of 24 blood samples will be taken at defined time points (baseline; 10; 20; 30; 40; 50; 60; 80; 100 min; 2.0; 2.5; 3.0; 3.5; 4.0; 4.5; 5.0; 5.5; 6.0; 6.5; 7.0; 7.5; 8.0; 9.0; 10.0 h). At each time point, blood will be collected (4.9 ml for separation of plasma) to determine fisetin, and its metabolites. The total amount of blood collected for each participant and each arm is 164 ml at the kinetic visits and 12 ml at the screening visit. After intake of fisetin, participants will drink 200 ml of sparkling water every hour to stimulate gastrointestinal peristalsis and to promote transport of the capsule. After 2 hours, the participants may drink a cup of tea or coffee and after 4 hours they will be served a meal low in fisetin content. Urine will be collected during the first 10 hours after fisetin administration. Monitoring of blood pressure and heart rate will take place for the first 4 hours after administration. Volunteers will stay in the Clinical Research Unit of the Institute of Pharmacology for the first 10 hours after administration.
Interventions
DIETARY_SUPPLEMENTFisetin - Fasted condition
A single oral dose of 500 mg fisetin (as Novusetin®) will be administered as 5 capsules with 240 ml of still water in the overnight fasting condition: A total of 24 blood samples will be taken at defined time points (baseline; 10; 20; 30; 40; 50; 60; 80; 100 min; 2.0; 2.5; 3.0; 3.5; 4.0; 4.5; 5.0; 5.5; 6.0; 6.5; 7.0; 7.5; 8.0; 9.0; 10.0 h). At each time point, blood will be collected (4.9 ml for separation of plasma) to determine fisetin, and fisetin metabolites. The total amount of blood collected for each participant and each arm is 164 ml at the kinetic visits and 12 ml at the screening visit. Urine will be collected during the first 10 hours after fisetin administration.
DIETARY_SUPPLEMENTFisetin - Fed condition
A single oral dose of 500 mg fisetin (as Novusetin®) will be administered as 5 capsules with 240 ml of still water in fed condition: Participants will eat a high-caloric and high-fat meal based on the recommendation of the FDA (Food and Drug Administration) for food-effect studies. This meal will contain two slices of toast with butter, two eggs fried in butter, approx. 113 g hash brown potatoes and 240 ml whole milk. A total of 24 blood samples will be taken at defined time points (baseline; 10; 20; 30; 40; 50; 60; 80; 100 min; 2.0; 2.5; 3.0; 3.5; 4.0; 4.5; 5.0; 5.5; 6.0; 6.5; 7.0; 7.5; 8.0; 9.0; 10.0 h). At each time point, blood will be collected (4.9 ml for separation of plasma) to determine fisetin, and fisetin metabolites. The total amount of blood collected for each participant and each arm is 164 ml at the kinetic visits and 12 ml at the screening visit. Urine will be collected during the first 10 hours after fisetin administration.
Sponsors
University Medicine Greifswald
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Masking description
This study is an opel-label study.
Intervention model description
The kinetic study will be designed as an open-label, two-cohorts (young vs. old), four-arm, randomized cross-over, single oral dose protocol.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* any sex * age between 18 and 30 years or ≥ 65 years * understands the study purpose and design * contractually capable and provides signed informed consent form * healthy condition or mild and/or well-treated forms of allergies, asthma, hypertension, and orthopedic diseases * a maximum of 3 chronically taken drugs
Exclusion criteria
* BMI \> 30 kg/m2 and \< 18 kg/m2 * body weight \< 48 kg * women in young cohort: known pregnancy or lactation period; positive urine pregnancy test at screening or kinetic visit * men: hemoglobin \< 8,3 mmol/l women: hemoglobin \< 7,3 mmol/l * elevated liver function tests (1 or more of ALAT, ASAT, yGT, Bilirubin \> 2x ULN) * reduced renal function (eGFRMDRD \< 60 ml/min/1,7 m2) * QTcF \> 450 ms in screening ECG * psychiatric disease requiring recent or actual treatment * drug dependency at the time of visit * use of recreational drugs more than twice a week * any known hypersensitivity or allergic reactions to fisetin * history of severe hypersensitivity reactions and/or anaphylaxis * poor venous conditions that make it impossible to place a peripheral venous catheter and regularly draw blood through it * intake of drugs undergoing extensive metabolism via CYP1A2, CYP2D6, CYP2C8, CYP2C9, CYP2C19, CYP3A4, and/or Pgp and with narrow (monitoring-requiring) therapeutic range during the past seven days if the duration of intake was at least two days * intake of COMT-inhibitors during the past seven days if the duration of intake was at least two days * intake of drugs or dietary supplements containing fisetin within the two days before or during the kinetic visits * individuals who have eaten food with high fisetin content in the two days before the kinetic visits (e.g. strawberry, apple, persimmon, grape, mango, kiwi, peach, tomato, onion, lotus roots, kale, cucumber; processed products, e.g. wine)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Fisetin plasma concentration arm 1 vs. arm 2 | 10 hours | Difference of fisetin plasma concentrations between the young and old cohort, expressed as area under the curve (AUC0-10h). |
| Fisetin plasma concentration arm 3 vs. arm 4 | 10 hours | Difference of fisetin plasma concentrations between the young and old cohort, expressed as area under the curve (AUC0-10h). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Fisetin metabolites plasma concentration arm 1 vs. arm 2 | 10 hours | Difference in plasma concentrations of fisetin metabolites between the young and old cohort, expressed as area under the curve (AUC0-10h). |
| Fisetin metabolites plasma concentration arm 3 vs. arm 4 | 10 hours | Difference in plasma concentrations of fisetin metabolites between the young and old cohort, expressed as area under the curve (AUC0-10h). |
| Fisetin plasma concentration arm 1 vs. arm 2 | 10 hours | Difference plasma concentrations of fisetin and fisetin metabolites between the young and old cohort, expressed as maximum plasma concentration (Cmax). |
| Fisetin plasma concentration arm 3 vs. arm 4 | 10 hours | Difference in plasma concentrations of fisetin and fisetin metabolites between the young and old cohort, expressed as maximum plasma concentration (Cmax). |
| Fisetin plasma concentration arm 1 vs. arm 3 | 10 hours | Difference of fisetin plasma concentrations between arm 1 and arm 3, expressed as area under the curve (AUC0-10h). |
| Fisetin plasma concentration arm 2 vs. arm 4 | 10 hours | Difference of fisetin plasma concentrations between arm 2 and arm 4, expressed as area under the curve (AUC0-10h). |
Countries
Germany
Contacts
CONTACTStefan Engeli, Prof.
Outcome results
None listed