Study on the Bioavailability of Three Different Prescription Processes of SHR4640 Tablets in Healthy Volunteers

Phase 1

• Conditions: Primary Gout; Hyperuricemia
• Interventions: Drug: SHR4640

• Registration Number: NCT04586803
• Lead Sponsor: Jiangsu HengRui Medicine Co., Ltd.

Brief Summary

The primary objective of the study is to evaluate the relative bioavailability of three different prescription processes of SHR4640 tablets in healthy volunteers. The secondary objective of the study is to observe the safety of SHR4640 tablets in healthy subjects.

Detailed Description

Study Type: Interventional Enrollment: Number of Subjects: 24 Type: Anticipated

Allocation : Yes Intervention Model : Single center, randomized, open Intervention Model Description: 3 cycles, 6 sequences Masking: No Masking

Subjects were randomly divided into the group A, B, C, D, E and F. On D1, D8 and D15, six groups of subjects were respectively given A version or C version or D version of SHR4640 tablet.

Study Timeline

• Study First Submitted: 2020-09-27
• Status Verified: 2020-10
• Study Start: 2020-10
• Study First Submitted QC: 2020-10-09
• Last Update Submitted: 2020-10-09
• Study First Posted: 2020-10-14
• Last Update Posted: 2020-10-14
• Primary Completion: 2020-11
• Study Completion: 2020-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: Male
• Target Recruitment: 24

Inclusion Criteria

• 1. Voluntarily sign the informed consent form before the start of the activities related to this trial, and be able to understand the procedures and methods of this trial, and be willing to strictly abide by the clinical trial plan to complete this trial; 2) Aged between 18 and 45 years old (including both ends, whichever is the time of signing the informed consent form), male; 3) Body weight ≥ 50 kg, and body mass index (BMI): 19-26 kg/m2 (both ends included).

Exclusion Criteria

• Subjects will not be allowed to enter this study if they meet any of the following criteria:

  1. General situation:

  2. Have a fertility plan within 3 months after screening to the last medication, or refuse to use medically approved contraceptive methods;

  3. Drug abusers or drug urine screening positive;

  4. Smokers (average daily smoking 5 or more) or urine Nicotin positive.

  5. The average daily alcohol intake during the first month was more than 25 g (for example, 750 mL beer, 250 mL wine or 50 mL low spirits);

  6. Anyone who had eaten grapefruit or fruit juice products within 2 days before administration, any food or drink containing caffeine (such as coffee, tea, chocolate, cola or other caffeinated carbonated drinks, etc.) and foods or drinks rich in purine food or alcohol.

  7. The researchers judged that the subjects had medical conditions that affected the absorption, distribution, metabolism and excretion of drugs or reduced compliance.

  8. Laboratory tests showed the following conditions:

  9. Those with sUA > 420 µmol / L during the screening period, or those with a previous history of hyperuricemia and / or gout;

  10. Those with estimated glomerular filtration rate (eGFR) < 90 during the screening period;

  11. Those with urolithiasis indicated or suspected by B ultrasound during the screening period;

  12. Those who were positive for hepatitis B surface antigen (HBsAg), anti-hepatitis C virus (HCV) antibody, human immunodeficiency virus (HIV) antibody or syphilis antibody within one month or during the screening period.

  13. There is any history of any of the following or concomitant diseases:

  14. Any clinical history of serious illness or disease or condition that the researchers believe may affect the results of the trial, including, but not limited to, a history of circulatory, endocrine, nervous, digestive, urinary or hematological, immune, mental and metabolic diseases.

  15. People with allergies, including those who are explicitly allergic to research drugs or any ingredient in research drugs, are allergic to any food ingredient or have special requirements for diet, and are unable to follow a uniform diet;

  16. Screening those who have undergone any operation within the first 3 months, or who have not recovered after the operation, or who may have a plan for operation or hospitalization during the trial;

  17. Those who donated blood (or lost blood) within the first 3 months and donated blood (or lost blood) more than 400 mL, or received blood transfusion.

  18. Use any of the following drugs or participate in clinical trials:

  19. Screen people who have participated in clinical trials of any drug or medical device within the previous 3 months;

  20. Take any prescription drug, over-the-counter medicine, Chinese herbal medicine or dietary supplement within 2 weeks before the screening period.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
D	SHR4640	Subjects were randomly divided into the group A, B, C, D, E and F. On D1, D8 and D15, six groups of subjects were respectively given A version or C version or D version of SHR4640 tablet.
E	SHR4640	Subjects were randomly divided into the group A, B, C, D, E and F. On D1, D8 and D15, six groups of subjects were respectively given A version or C version or D version of SHR4640 tablet.
A	SHR4640	Subjects were randomly divided into the group A, B, C, D, E and F. On D1, D8 and D15, six groups of subjects were respectively given A version or C version or D version of SHR4640 tablet.
B	SHR4640	Subjects were randomly divided into the group A, B, C, D, E and F. On D1, D8 and D15, six groups of subjects were respectively given A version or C version or D version of SHR4640 tablet.
C	SHR4640	Subjects were randomly divided into the group A, B, C, D, E and F. On D1, D8 and D15, six groups of subjects were respectively given A version or C version or D version of SHR4640 tablet.
F	SHR4640	Subjects were randomly divided into the group A, B, C, D, E and F. On D1, D8 and D15, six groups of subjects were respectively given A version or C version or D version of SHR4640 tablet.

Primary Outcome Measures

Name	Time	Method
AUC0-inf(if available)	Day1 to Day25	Area under the curve from time 0 to infinity
Cmax	Day1 to Day25	Peak plasma concentration
AUC0-t	Day1 to Day25	Area under the curve from the time of dosing. Dosing time to the last measurable (positive) concentration.

Secondary Outcome Measures

Name	Time	Method
t1/2	Day1 to Day25	Half time
CL/F	Day1 to Day25	apparent clearance
PD	Day1 to Day25	concentration of serum urine acid
Tmax	Day1 to Day25	Time of maximum observed concentration
Vz/F	Day1 to Day25	apparent volume of distribution