Single Dose Study of SHR4640 in Healthy Subjects

Study Overview
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Brief Summary
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The objective of the study is to assess the safety, tolerance, food effect, pharmacokinetic and pharmacodynamic properties of single dose adminstration of SHR4640 in healthy volunteers.

Official Title
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A Phase 1, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate Safety, Tolerability, Food Effect, Pharmacokinetics, and Pharmacodynamics of Single Doses of SHR4640 in Healthy Subjects

Conditions
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Gout; Hyperuricemia

Intervention / Treatment
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* Drug: SHR4640
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Body weight≥50, BMI:19-24kg/m2; Screening serum urate level ≤ 4.5 mg/dL for male and ≤ 3.5 mg/dL for female; Medically stable based on physical examination, medical history, laboratory results, vital sign measurements, and 12-lead electrocardiogram (ECG) at screening; Exclusion Criteria: History of hyperuricemia or gout. Pregnancy or breastfeeding; History or suspicion of kidney stones; serum creatinine>1.5mg/dl for male, >1.2mg/dl for female; alanine aminotransferase and/or aspartate aminotransferase>2 upper limit of normal, or total bilirubin>2.5 upper limit of normal.

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: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>2.5-mg SHR4640 or placebo | Drug: SHR4640<br> <br> Drug: Placebo<br> <br> |
| Experimental: Cohort 2<br>5-mg SHR4640 or placebo | Drug: SHR4640<br> <br> Drug: Placebo<br> <br> |
| Experimental: Cohort 3<br>7.5-mg SHR4640 or placebo | Drug: SHR4640<br> <br> Drug: Placebo<br> <br> |
| Experimental: Cohort 4<br>10-mg SHR4640 or placebo | Drug: SHR4640<br> <br> Drug: Placebo<br> <br> |
| Experimental: Cohort 5<br>20-mg SHR4640 or placebo | Drug: SHR4640<br> <br> Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events |  | Clinical significant changes from baseline up to to Day 15; from baseline up to Day 19 for 7.5mg dose group | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak Plasma Concentration (Cmax) |  | up to day 4; up to day 11 for 7.5mg dose group | 
| Area under the plasma concentration versus time curve (AUC) |  | up to day 4; up to day 11 for 7.5mg dose group | 
| Half-time (T1/2) |  | up to day 4; up to day 11 for 7.5mg dose group | 
| Time to the peak plasma concentration (Tmax) |  | up to day 4; up to day 11 for 7.5mg dose group | 
| Cmax of SHR4640 dosed after high-fat meal in 7.5mg dose group |  | up to day 11 | 
| AUC of SHR4640 dosed after high-fat meal in 7.5mg dose group |  | up to day 11 | 
| T1/2 of SHR4640 dosed after high-fat meal in 7.5mg dose group |  | up to day 11 | 
| Tmax of SHR4640 dosed after high-fat meal in 7.5mg dose group |  | up to day 11 | 
| Changes in serum uric acid concentration from baseline | absolute and percent changes in serum acid concentration | up to day 4; up to day 11 for 7.5mg dose group | 
| Changes in urinary uric acid excretion from baseline | percent changes in urinary uric acid excretion from baseline | up to day 4; up to day 11 for 7.5mg dose group | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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urate transporter 1, SHR4640, single ascending dose, pharmacokinetics, pharmacodynamics