Trial of Chiauranib Capsule on Pharmacokinetics to Assess the Effect of High Fat Diet in Healthy Volunteers

Study Overview
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Brief Summary
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The purpose of this study is to further study the pharmacokinetic characteristics of Chiauranib Capsule in Healthy Volunteers with High Fat Diet.

Detailed Description
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This study is a Randomized, Open-label, Single-dose, Single-center, two-sequence, two- stage Phase I Trial. 16 Healthy Volunteers will be enrolled and Randomized into two arms. 8 Healthy Volunteers were in each arm. Arm A：Patients receive 50mg Chiauranib po only once In the fasting state and after 14 days receive 50mg Chiauranib po Only once with High Fat Diet. Arm B: Patients receive 50mg Chiauranib po only once with High Fat Diet and after 14 days receive 50mg Chiauranib po Only once In the fasting state. During the trial, Blood samples were collected.

Official Title
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A Randomized, Open-label, Single-dose, Single-center, Two-sequence, Two- Stage Phase I Trial of Chiauranib Capsule on Pharmacokinetics to Assess the Effect of High Fat Diet in Healthy Volunteers

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: Chiauranib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ages: 18 Years to 45 Years 19≤BMI≤26. Weight of male ≥50 kg and Weight of female 45 kg at screening Healthy or NCS as determined by the Investigator based on physical examination, vital signs, a series of laboratory examinations（such as blood routine examination, et.al）and 12-lead electrocardiogram (ECG) Healthy Volunteers have no plan to fertilize throughout treatment and for at least 6 months after study is stopped Healthy Volunteers voluntarily sign informed consent Able to communicate well with the Investigator, to comply with the requirements of the study Exclusion Criteria: Has known allegies to Chiauranib ,any of the excipients or Have a history of relevant atopy or drug hypersensitivity Being hypertension or having risk of hypertension, or SBP≥140 mmHg, DBP ≥90 mmHg; or Being hypotension or having risk of hypotension, or SBP < 90 mmHg, DBP < 60 mmHg Inability to take oral medication or having Gastrointestinal, liver and kidney diseases that affect drug absorption or metabolism within 6 months Prior to random Having uncured diarrhea or having 4 or more episodes of diarrhea within 7 days prior to scheduled drug administration Having any significant history of hemorrhagic disease or any history of coagulopathy A history of frequent and severe infection(≥3 episodes)within the past 1 year, or a history of severe infection within 3 months prior to drug administration； Ccr < 80 mL/min Difficulty of venous blood collection QTcF > 450 ms Drug abuse within 5 years or used drug within 3 months prior to the study, or Urine drug screening is positive during screening Heavy smokers(average daily smoking of more than 5 cigarettes/ day during past 3 months prior to screenig); heavy drinkers(average weekly drinking of more than 14 units of alcohol during past 6 months prior to screening, 1 unit =360 mL beer or 45 mL 40% spirits or 150 mL wine); Having Alcoholic products within 2 days prior to drug administration, or Alcohol breath test result ≥20 mg/dl Ingestion of prescription drugs, OTC drug, Vitamin, dietary supplements or herbal products within 14 days prior to screening Subjects who have taken any drugs known to induce or inhibit hepatic drug metabolism(CYP3A, CYP1A2 and CYP2D6)within 30 days prior to drug administration of the study medication, or Subjects who have taken any foods and drinks known to induce or inhibit hepatic drug metabolism within 7 days prior to drug administration Intake of Tea, Coffee or other Caffeinated beverage(more than 8 cups, 1 cup=250 mL)within 14 days prior to drug administration, Intake of any food or beverage containing or metabolized to produce caffeine or xanthine within 48 hours prior to drug administration Subjects with clinically relevant evidence of cardiovascular, gastrointestinal/hepatic, renal, psychiatric, respiratory, urogenital, hematologic/immunologic, HEENT (head, ears, eyes, nose, throat), dermatological/connective tissue, musculoskeletal, metabolic/nutritional, drug hypersensitivity, allergy, endocrine, major surgery or other relevant diseases as revealed by medical history, physical examination, and laboratory assessments which may interfere with the absorption, distribution, metabolism or elimination of drugs or constitute a risk factor when taking study medication A positive result in hepatitis B surface antigen (HBsAg), anti-hepatitis C virus (HCV) antibodies, a syphilis test, or an human immunodeficiency virus (HIV) test The abnormal result of C-reactive protein has clinical significance or Subjects testing positive for COVID-19 Vaccinated within 1 month prior to screening or plan to Vaccinate during the study Females with a positive pregnancy test or Women of childbearing potential, pregnant and lactating women Volunteer in any other study within 3 months prior to drug administration, or Volunteer in 3 times or more studies Blood donation or lost more than 400mL blood within 3 months prior to the study, or Received blood transfusions within 1 month Patients received major surgical operations within 6 months prior to screening, or plan to received surgical operation during the study Extremes in food consumption practices Other situations that the researchers considered unsuitable to enroll the subject

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 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 |
| --- | --- |
| Other: Chiauranib(In the fasting state)<br>Experimental: Chiauranib Patients receive 50mg Chiauranib po only once In the fasting state and after 14 days receive 50mg Chiauranib po Only once with High Fat Diet | Drug: Chiauranib<br>* 50mg po only once<br>|
| Other: Chiauranib(In the high fat diet state)<br>Experimental: Chiauranib Patients receive 50mg Chiauranib po only once with High Fat Diet and after 14 days receive 50mg Chiauranib po Only once In the fasting state | Drug: Chiauranib<br>* 50mg po only once<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics of Chiauranib (in plasma) | Peak plasma concentration for Chiauranib(Cmax) | up to 20 Days | 
| Pharmacokinetics of Chiauranib (in plasma) | Area under the concentration-time curve from zero to last quantificable concentration for Chiauranib (AUC0-t) | up to 20 Days | 
| Pharmacokinetics of Chiauranib (in plasma) | Area under the concentration-time curve from zero extrapolated to infinity for Chiauranib（AUC0-inf） | up to 20 Days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics of Chiauranib (in plasma) | Time to Cmax for Chiaruanib（Tmax） | up to 20 Days | 
| Pharmacokinetics of Chiauranib (in plasma) | Elimination half-life（t1/2） | up to 20 Days | 
| Pharmacokinetics of Chiauranib (in plasma) | Apparent clearance（CL/F） | up to 20 Days | 
| Pharmacokinetics of Chiauranib (in plasma) | Apparent volume of distribution（Vd/F） | up to 20 Days | 
| Pharmacokinetics of Chiauranib (in plasma) | Elimination rate constant（λz） | up to 20 Days |