Pharmacokinetics Study of Antitumor B in Healthy Volunteers

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the single-dose oral pharmacokinetics of an herbal supplement - Antitumor B - in healthy subjects.

Detailed Description
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Antitumor B (ATB), also known as Zeng Sheng Ping, is a Chinese herbal mixture composed of six plants: Sophora tonkinensis, Polygonum bistorta, Prunella vulgaris, Sonchus brachyotus, Dictamnus dasycarpus, and Dioscorea bulbifera. ATB is available as 300 mg tablets and has been traditionally used in China for dysplasia (dose 4-8 tables/ twice daily). Several studies in rodents and humans have been published demonstrating the chemopreventive activity of ATB against various cancers (e.g. lung, esophageal and oral). However, the investigators currently do not know what pharmacologically relevant concentration levels can be achieved systemically for different components of ATB in humans. Since it is a complex herbal mixture containing various key active components (KACs), relative levels of KACs in the ATB mixture can influence the bioavailability and pharmacokinetic of the individual KACs. The proposed study aim to estimate the plasma concentration of four key active components in a tablet with a chemical-defined ATB mixture. The investigators are interested in doing a human single-dose (8 tablets once) full pharmacokinetic study of ATB tablets. The investigators plan to collect 9 blood and 9 saliva samples from 8 healthy volunteers over a period of 24 hours (at pre-dose, 0.5, 1, 2, 3, 4, 6, 8, and 24 hours) to determine the saliva and plasma concentration of four key constituents of ATB (matrine, dictamnine, maackiain, fraxinellone) and develop the in vivo correlation between plasma and saliva concentrations

Official Title
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Pharmacokinetics Study of Antitumor B in Healthy Volunteers

Conditions
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Healthy Adults

Intervention / Treatment
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* Dietary Supplement: Antitumor B


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A potential subject must meet all the following inclusion criteria to be eligible to participate in the study. Health questionnaire filled on the day of recruitment, after signing the written consent form Participants must receive administration of study agent within 21-28 calendar days of being selected as subject after screening procedure is completed Healthy male or female subjects aged ≥18 and ≤40 years of age Subjects must have a body mass index (BMI) between 18.0-29.9 kg/m² inclusive CBC/differential obtained within 14 calendar days prior to selection as subject for drug administration , with adequate bone marrow function defined as follows: Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3; Platelets ≥ 100,000 cells/mm3; Hemoglobin ≥ 8.0 g/dl (Note: The use of transfusion or other intervention to achieve Hgb ≥ 8.0 g/dl is acceptable.); Adequate renal and hepatic function within 14 calendar days prior to selection as subject for drug administration defined as follows: Serum creatinine < 1.5 mg/dl or creatinine clearance (CCr) ≥ 50 ml/min within 14 calendar days prior to selection as subject for drug administration, determined by 24-hour collection or estimated by Cockcroft-Gault formula: CCr male = [(140 - age) x (wt in kg)] [(Serum Cr mg/dl) x (72)] CCr female = 0.85 x (CrCl male) Total bilirubin < 2 x the institutional Upper limit of Normal range (ULN) within 14 calendar days prior to selection as subject for drug administration AST or ALT ≤ 3 x the institutional ULN within 14 calendar days prior to selection as subject for drug administration ALP or GGT ≤ 2.5 x the institutional ULN within 14 calendar days prior to selection as subject for drug administration Magnesium, calcium, glucose, potassium, and sodium within 14 calendar days prior to selection as subject for drug administration, with the following required parameters: Magnesium: > 0.9 mg/dl or < 3 mg/dl; Calcium: > 7 mg/dl or < 12.5 mg/dl; Glucose: > 40 mg/dl or < 250 mg/dl; Potassium: > 3 mmol/L or < 6 mmol/L; Sodium: > 130 mmol/L or < 155 mmol/L. Participant must have active health insurance coverage at the time of study Participants must be able to understand study-specific information and instructions in English. Participant must be willing to fully comply with study procedures and restrictions. Participant must be able to provide written, personally signed, and dated informed consent to participate in the study, in accordance with the ICH Good Clinical Practice (GCP) Guideline E6 (1996) and applicable regulations, before completing any studyrelated procedures Exclusion Criteria: History of active liver disease or cancer. Severe current or recurrent comorbidity such as (e.g., cardiovascular, haematological, neurological, endocrine, renal, liver, GI, HIV-AIDS, or other conditions such as cancer) that could affect the absorption and/or disposition of ATB Any disease/illness diagnosed by a licensed physician. Blood report positive for HIV and/or Hepatitis B and C tests Has had an acute illness within two weeks prior to screening. Pregnant or lactating women are ineligible due to unforeseeable risks to embryo or fetus. Concurrent use of any prescription medication (including medicinal botanical) except birth control pills, over the counter medication and supplements except Vitamins and mineral supplements, or herbal supplements in form of herbal mixtures, teas or individual compounds (such as querctein, curcumin, echinacea, flaxseed, ginseng, ginkgo, soy etc.) that the study PI believes could potentially impact the results/objectives of this study. Concurrent use of recreational drugs or alcohol during the study (self-declared by study participants) Prisoners Economically and/or educationally disadvantaged persons

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Healthy volunteer<br>In good general health and feeling well (no diagnosed disorders/illnesses) At least 18 years old BMI in the range of 18-29.9 kg/m² No known history of substance abuse No known allergies to food/drug | Dietary Supplement: Antitumor B<br>* Single dose 2400 mg<br>* Other names: ATB;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax of matrine, dictamnine, maackiain and fraxinellone in plasma | Maximum (peak) observed drug concentration in plasma | Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, and 24 hours post dose | 
| Cmax of matrine, dictamnine, maackiain and fraxinellone in saliva | Maximum (peak) observed drug concentration in saiva | Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, and 24 hours post dose | 
| Tmax of matrine, dictamnine, maackiain and fraxinellone in plasma | Time of Maximum (peak) observed drug concentration in plasma | Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, and 24 hours post dose | 
| Tmax of matrine, dictamnine, maackiain and fraxinellone in saliva | Time of Maximum (peak) observed drug concentration in saliva | Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, and 24 hours post dose | 
| AUC0-24 of matrine, dictamnine, maackiain and fraxinellone in plasma | Area under the curve of plasma concentration-time profile | Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, and 24 hours post dose | 
| AUC0-24 of matrine, dictamnine, maackiain and fraxinellone in saliva | Area under the curve of saliva concentration-time profile | Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, and 24 hours post dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma-saliva IVIVC | In vivo-in vivo correlation established between plasma and saliva concentrations | Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, and 24 hours post dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pharmacokinetics, Antitumor B, healthy volunteer