Phase I Pharmacokinetic Study of HUYPS-1 in Healthy Volunteers

Study Overview
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Brief Summary
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Fasting Period: At least 10 hours prior to dosing until 4 hours post-dose of each study period. Period: 24 hours post dose in each period. Each subject will complete two study periods. Washout Period: At least one week after dosing of the previous period. Confinement: From at least 10 hours prior to dosing until at least 12 hours post-dose, for a total of at least 22 hours for each study period.

Detailed Description
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This study is a single center and open-label design to evaluate tolerability, safety and pharmacokinetic properties of HUYPS-1 after single oral administration in healthy subjects under fasting conditions. A total of 14 eligible subjects are expected to be enrolled to ensure 12 evaluable subjects. The study will be completed when there are at least 12 evaluable subjects. The evaluable subjects are those who have completed both periods. Eligible subjects will be randomly assigned to either of the two treatment sequences. The study design in a 2-sequence, 2-period crossover design. There is at least 7-day washout time between periods. The formulation of HUYPS-1 for oral administration contains 100 mg mannitol and 100 mg sucralose per tablet will be given by one or nine tablets per person of each period. Mannitol and sucralose are both commonly used excipients approved by WHO. These excipients are included in the FDA Inactive Ingredients Guide, GRAS (generally recognized as safe) and commonly used pharmaceutical excipients, therefore the oral doses of these excipients can be regarded as extremely safe in this study.

Official Title
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A Randomized, Open-label, Single Dose, Crossover Design Phase I Study to Evaluate Tolerability, Safety and Pharmacokinetics of HUYPS-1 in Healthy Volunteers

Conditions
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Nonalcoholic Steatohepatitis

Intervention / Treatment
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* Drug: HUYPS-1 one tablet
* Drug: HUYPS-1 nine tablets


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Normal healthy adult subjects between 20-50 years of age. Acceptable medical history and physical examination including: Acceptable clinical laboratory determinations without significant deviation from normal values within two months prior to Period I dosing, which includes AST (SGOT), ALT (SGPT), r-GT, alkaline phosphatase, total bilirubin, albumin, glucose, BUN, uric acid, creatinine, total cholesterol, triglyceride (TG) and galactose single point (GSP). Acceptable hematology within two months prior to the study, which includes hemoglobin, hematocrit, red blood cells, MCV, MCH, MCHC, white blood cells, differential white blood cells and platelets. Acceptable urinalysis within two months prior to the study, which includes pH, blood, glucose and protein. Signed the written informed consent to participate in this study. Acceptable body mass index (BMI): 18.5 < BMI < 25 kg/m2 Exclusion Criteria: Recent history of drug or alcohol addiction or abuse within the past year. A clinically significant disorder involving the cardiovascular, respiratory, renal, gastrointestinal, immunologic, hematologic, endocrine or neurologic system(s) or psychiatric disease (as determined by the clinical investigator). History of allergic response(s) to mannitol, sucralose or related drugs. History of clinically significant allergies including drug allergies or allergic bronchial asthma. Evidence of chronic or acute infectious diseases. Any clinically significant illness or surgery during the one month prior to Period I dosing (as determined by the clinical investigator). Taking any drug known to induce or inhibit hepatic drug metabolism within one month prior to the beginning of the study. Receiving any investigational drug within one month prior to Period I dosing. Taking any prescription medication or any nonprescription medication within two weeks prior to Period I doing. Donating greater than 150 mL of blood within two months prior to Period I dosing or donating plasma (e.g. plasmapheresis) within two weeks prior to Period I dosing. All subjects will be advised not to donate blood for four weeks after completing the study. Consumption of caffeine, xanthine-containing products (i.e. coffee, tea, caffeine-containing sodas, colas and chocolate, etc.) and/or alcohol, smoke or use tobacco products within 48 hours prior to days on which dosing is scheduled and during the periods when blood samples are being collected. Any other medical reason as determined by the clinical investigator. Subject is pregnant or breastfeeding. Women of childbearing potential disagree to use an acceptable method of contraception (e.g., hormonal contraceptives, IUD, barrier device or abstinence) throughout the study.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 50 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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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Healthy Volunteers dose 1<br>Evaluate tolerability, safety and pharmacokinetic properties of HUYPS-1 after 1 tablet oral administration in healthy subjects | Drug: HUYPS-1 one tablet<br>* After 7-day washout time, subjects will receive HUYPS-1 1 tablet.<br>|
| Experimental: Healthy Volunteer dose 2<br>Evaluate tolerability, safety and pharmacokinetic properties of HUYPS-1 after 9 tablets oral administration in healthy subjects | Drug: HUYPS-1 nine tablets<br>* After 7-day washout time, subjects will receive HUYPS-1 9 tablets.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs): | An AE is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged in-patient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. | 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic profile of maximum concentration of HUYPS-1 (Cmax) | Concentrations of HUYPS-1 and it metabolites in plasma and urine will be measured by a specific and sensitive LC/MS/MS method developed in the laboratory of Clinical Pharmacokinetic Laboratory of Tri-Service General Hospital. According to the pharmacokinetic parameters of HUYPS-1 and its metabolites in health subjects oral HUYPS-1 to assess the safety information.The study will be conducted to validate the precision, accuracy (including with-run and between-run variation), linearity, specificity, reproducibility, limit of quantitation based on recovery studies. Assays will be performed in the laboratory of Clinical Pharmacokinetic Laboratory of Tri-Service General Hospital. Spiked samples of known concentrations will be analyzed together for quality control of the assay method. The following parameters of HUYPS-1 will be determined using WINNONLINTM: Cmax | 24 hours | 
| Pharmacokinetic profile of time of occurrence for maximum (peak) HUYPS-1 concentration (Tmax) | Concentrations of HUYPS-1 and it metabolites in plasma and urine will be measured by a specific and sensitive LC/MS/MS method developed in the laboratory of Clinical Pharmacokinetic Laboratory of Tri-Service General Hospital. According to the pharmacokinetic parameters of HUYPS-1 and its metabolites in health subjects oral HUYPS-1 to assess the safety information.The study will be conducted to validate the precision, accuracy (including with-run and between-run variation), linearity, specificity, reproducibility, limit of quantitation based on recovery studies. Assays will be performed in the laboratory of Clinical Pharmacokinetic Laboratory of Tri-Service General Hospital. Spiked samples of known concentrations will be analyzed together for quality control of the assay method. The following parameters of HUYPS-1 will be determined using WINNONLINTM: Tmax | 24 hours | 
| Pharmacokinetic profile of area under curve (AUC0-t) for HUYPS-1 | Concentrations of HUYPS-1 and it metabolites in plasma and urine will be measured by a specific and sensitive LC/MS/MS method developed in the laboratory of Clinical Pharmacokinetic Laboratory of Tri-Service General Hospital. According to the pharmacokinetic parameters of HUYPS-1 and its metabolites in health subjects oral HUYPS-1 to assess the safety information.The study will be conducted to validate the precision, accuracy (including with-run and between-run variation), linearity, specificity, reproducibility, limit of quantitation based on recovery studies. Assays will be performed in the laboratory of Clinical Pharmacokinetic Laboratory of Tri-Service General Hospital. Spiked samples of known concentrations will be analyzed together for quality control of the assay method. The following parameters of HUYPS-1 will be determined using WINNONLINTM: AUC0-t | 24 hours | 
| Pharmacokinetic profile of area under curve infinity (AUCINF) for HUYPS-1 | LC/MS/MS method developed in the laboratory of Clinical Pharmacokinetic Laboratory of Tri-Service General Hospital. According to the pharmacokinetic parameters of HUYPS-1 and its metabolites in health subjects oral HUYPS-1 to assess the safety information.The study will be conducted to validate the precision, accuracy (including with-run and between-run variation), linearity, specificity, reproducibility, limit of quantitation based on recovery studies. Assays will be performed in the laboratory of Clinical Pharmacokinetic Laboratory of Tri-Service General Hospital. Spiked samples of known concentrations will be analyzed together for quality control of the assay method. The following parameters of HUYPS-1 will be determined using WINNONLINTM: AUCINF | 24 hours | 
| Pharmacokinetic profile of overall HUYPS-1 elimination rate constant (k) | LC/MS/MS method developed in the laboratory of Clinical Pharmacokinetic Laboratory of Tri-Service General Hospital. According to the pharmacokinetic parameters of HUYPS-1 and its metabolites in health subjects oral HUYPS-1 to assess the safety information.The study will be conducted to validate the precision, accuracy (including with-run and between-run variation), linearity, specificity, reproducibility, limit of quantitation based on recovery studies. Assays will be performed in the laboratory of Clinical Pharmacokinetic Laboratory of Tri-Service General Hospital. Spiked samples of known concentrations will be analyzed together for quality control of the assay method. The following parameters of HUYPS-1 will be determined using WINNONLINTM: k | 24 hours | 
| Pharmacokinetic profile of elimination half-life (T1/2) for HUYPS-1 | LC/MS/MS method developed in the laboratory of Clinical Pharmacokinetic Laboratory of Tri-Service General Hospital. According to the pharmacokinetic parameters of HUYPS-1 and its metabolites in health subjects oral HUYPS-1 to assess the safety information.The study will be conducted to validate the precision, accuracy (including with-run and between-run variation), linearity, specificity, reproducibility, limit of quantitation based on recovery studies. Assays will be performed in the laboratory of Clinical Pharmacokinetic Laboratory of Tri-Service General Hospital. Spiked samples of known concentrations will be analyzed together for quality control of the assay method. The following parameters of HUYPS-1 will be determined using WINNONLINTM: T1/2 | 24 hours | 
| Pharmacokinetic profile of mean residence time (MRT) for HUYPS-1 | LC/MS/MS method developed in the laboratory of Clinical Pharmacokinetic Laboratory of Tri-Service General Hospital. According to the pharmacokinetic parameters of HUYPS-1 and its metabolites in health subjects oral HUYPS-1 to assess the safety information.The study will be conducted to validate the precision, accuracy (including with-run and between-run variation), linearity, specificity, reproducibility, limit of quantitation based on recovery studies. Assays will be performed in the laboratory of Clinical Pharmacokinetic Laboratory of Tri-Service General Hospital. Spiked samples of known concentrations will be analyzed together for quality control of the assay method. The following parameters of HUYPS-1 will be determined using WINNONLINTM: MRT | 24 hours | 
| Pharmacokinetic profile of clearance (CL/F) for HUYPS-1 | LC/MS/MS method developed in the laboratory of Clinical Pharmacokinetic Laboratory of Tri-Service General Hospital. According to the pharmacokinetic parameters of HUYPS-1 and its metabolites in health subjects oral HUYPS-1 to assess the safety information.The study will be conducted to validate the precision, accuracy (including with-run and between-run variation), linearity, specificity, reproducibility, limit of quantitation based on recovery studies. Assays will be performed in the laboratory of Clinical Pharmacokinetic Laboratory of Tri-Service General Hospital. Spiked samples of known concentrations will be analyzed together for quality control of the assay method. The following parameters of HUYPS-1 will be determined using WINNONLINTM: CL/F | 24 hours | 
| Pharmacokinetic profile of apparent volume (Vd/F) for HUYPS-1 | LC/MS/MS method developed in the laboratory of Clinical Pharmacokinetic Laboratory of Tri-Service General Hospital. According to the pharmacokinetic parameters of HUYPS-1 and its metabolites in health subjects oral HUYPS-1 to assess the safety information.The study will be conducted to validate the precision, accuracy (including with-run and between-run variation), linearity, specificity, reproducibility, limit of quantitation based on recovery studies. Assays will be performed in the laboratory of Clinical Pharmacokinetic Laboratory of Tri-Service General Hospital. Spiked samples of known concentrations will be analyzed together for quality control of the assay method. The following parameters of HUYPS-1 will be determined using WINNONLINTM: Vd/F | 24 hours | 
| Pharmacokinetic profile of area under moment curve (AUMC(0-t)) for HUYPS-1 | LC/MS/MS method developed in the laboratory of Clinical Pharmacokinetic Laboratory of Tri-Service General Hospital. According to the pharmacokinetic parameters of HUYPS-1 and its metabolites in health subjects oral HUYPS-1 to assess the safety information.The study will be conducted to validate the precision, accuracy (including with-run and between-run variation), linearity, specificity, reproducibility, limit of quantitation based on recovery studies. Assays will be performed in the laboratory of Clinical Pharmacokinetic Laboratory of Tri-Service General Hospital. Spiked samples of known concentrations will be analyzed together for quality control of the assay method. The following parameters of HUYPS-1 will be determined using WINNONLINTM: AUMC(0-t) | 24 hours | 
| Pharmacokinetic profile of area under moment curve infinity (AUMCINF) for HUYPS-1 | LC/MS/MS method developed in the laboratory of Clinical Pharmacokinetic Laboratory of Tri-Service General Hospital. According to the pharmacokinetic parameters of HUYPS-1 and its metabolites in health subjects oral HUYPS-1 to assess the safety information.The study will be conducted to validate the precision, accuracy (including with-run and between-run variation), linearity, specificity, reproducibility, limit of quantitation based on recovery studies. Assays will be performed in the laboratory of Clinical Pharmacokinetic Laboratory of Tri-Service General Hospital. Spiked samples of known concentrations will be analyzed together for quality control of the assay method. The following parameters of HUYPS-1 will be determined using WINNONLINTM: AUMCINF | 24 hours |