Single Dose Study of SHR4640 in Healthy Subjects

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

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.

Study Overview

• Status: Completed
• Conditions: Gout; Hyperuricemia
• Intervention / Treatment: Drug: Placebo; Drug: SHR4640

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Sichuan
    • Chongqing, Sichuan, China, 400038
      • Southwest Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

5

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Jiangsu HengRui Medicine Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2015
• Primary Completion (Actual): February 1, 2017
• Study Completion (Actual): February 1, 2017

Study Registration Dates

• First Submitted: April 27, 2016
• First Submitted That Met QC Criteria: June 23, 2016
• First Posted (Estimate): June 28, 2016

Study Record Updates

• Last Update Posted (Actual): February 28, 2017
• Last Update Submitted That Met QC Criteria: February 26, 2017
• Last Verified: June 1, 2016

More Information

Terms related to this study

• Keywords: pharmacokinetics; pharmacodynamics; single ascending dose; urate transporter 1; SHR4640
• Additional Relevant MeSH Terms: Pathologic Processes; Hyperuricemia
• Other Study ID Numbers: SHR4640-101

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No