Multiple Doses Study of SHR4640 in Male Subjects With High Serum Uric Acid Level

NCT03211403 | Completed Phase 1

• 1 other identifier: SHR4640-102-AUS
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-Center, randomized, double-Blind, placebo-controlled, multiple ascending-dose Phase I trail.

Conditions

Gout; Hyperuricemia

Outcome Measures

Primary Outcomes (6)

• Incidence of Adverse events in terms of changes in Hematology

  Hemoglobin Hematocrit Erythrocytes count Mean cell volume, Mean cell hemoglobin concentration, Leukocytes count, Neutrophils count, Lymphocytes count, Monocytes count, Eosinophils count, Basophils count, Platelets count

  Up to Day 14

• Incidence of Adverse events in terms of changes in Urinalysis

  Urobilinogen Dipstick urinalysis, including: pH, Specific gravity, Protein, Blood, Leukocytes, Glucose, Ketones, Bilirubin, Nitrites

  Up to Day 14

• Incidence of Adverse events in terms of changes in Biochemistry (fasting)

  Including Serum creatinine, Urea, Alanine aminotransferase, Aspartate aminotransferase, Gamma glutamyl transferase, Total bilirubin, Total protein, Albumin, Alkaline phosphatase, Serum uric acid, Glucose, Triglycerides, Total cholesterol, High-density lipoprotein cholesterol, Low-density lipoprotein cholesterol

  Up to Day 14

• Incidence of Adverse events in terms of changes in Physical examinations

  Review of body weight and height; general appearance; head; eyes; ears/nose/throat; neck; lymph nodes; neurological and musculoskeletal systems; heart; lungs; abdomen; skin; and extremities

  Up to Day 14

• Incidence of Adverse events in terms of changes in Vital signs

  Oral temperature, respiratory rate, blood pressure, and pulse rate

  Up to Day 14

• Incidence of Adverse events in terms of changes in 12-lead ECGs

  The 12-lead ECGs must be recorded after the subjects have rested in the supine position for 5 minutes to ensure a stable baseline.

  Up to Day 14

Secondary Outcomes (6)

• Peak Plasma Concentration (Cmax) (of single dose and at stable status)

  Up to Day 10

• Area under the plasma concentration versus time curve (AUC) (of single dose and at stable status)

  Up to Day 10

• Half-time (T1/2) (of single dose and at stable status)

  Up to Day 10

• Time to the peak plasma concentration (Tmax) (of single dose and at stable status)

  Up to Day 10

• Changes in serum uric acid concentration from baseline

  Up to Day 10

Study Arms (3)

SHR4640 2.5mg

EXPERIMENTAL

6 subjects assigned to 2.5mg SHR4640 and 2 subjects assigned to placebo

Drug: SHR4640

SHR4640 10mg

EXPERIMENTAL

6 subjects assigned to 10mg SHR4640 and 2 subjects assigned to placebo

Drug: SHR4640

SHR4640 20mg

EXPERIMENTAL

6 subjects assigned to 20mg SHR4640 and 2 subjects assigned to placebo

Drug: SHR4640

Interventions

SHR4640 DRUG

SHR4640 or placebo once daily for a week

SHR4640 10mg; SHR4640 2.5mg; SHR4640 20mg

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male, aged between 18 and 65 years, inclusive.
• Body weight ≥ 50 kg and body mass index between 18.0 and 35.0 kg/m2, inclusive.
• Screening sUA level ≥0.36 mmol/L.
• Considered generally healthy upon completion of medical history, full physical examination, vital signs, laboratory parameters (including thyroid function and serological tests, hematology, urinalysis, and biochemistry), 12-lead ECG, and abdominal ultrasound, as judged by the Investigator.
• Agrees to use a highly effective method of contraception, i.e. condom and suitable contraception for his female partner e.g. oral contraceptive or intrauterine contraceptive device during heterosexual intercourse or be non-heterosexually active, or practice sexual abstinence throughout the study period and for 30 days following final dose of study drug, and must agree to refrain from sperm donation from Day -2 until at least 30 days following final dose of study drug.
• Negative drug screen (including alcohol) at screening and on admission to clinical site.
• Able to understand the study procedures and the risks involved and must be willing to provide a written informed consent before any study-related activity.

You may not qualify if:

• History of hypersensitivity to SHR4640 or its analogues.
• History of gout.
• Screening alanine aminotransferase, aspartate aminotransferase, total bilirubin, or gamma glutamyl transferase \> 1.5 × upper limit of normal.
• Positive result for human immunodeficiency virus (HIV).
• Positive result for hepatitis B surface antigen or hepatitis C virus antibody.
• History or presence of kidney stones.
• Acute or chronic illness that, in the opinion of the Investigator, might confound the results of the trial or pose risk to the subject when administering the trial product.
• Undergone major surgery within 3 months of Day 1 or has surgery planned during study participation.
• Donated any blood or plasma in the past month or more than 400 mL within 3 months of Day 1.
• Has unsuitable venous for blood sampling.
• Use of tobacco products within 30 days of Day 1.
• Heavy caffeine drinker (more than 5 cups or glasses of caffeinated beverages per day).
• History of drug and/or alcohol abuse in the last year.
• Consumes more than 14 units of alcohol per week (1 unit = 250 mL beer, 25 mL of 40% spirits and 125 mL glass of wine).
• Consumes grapefruit and/or poppy seed within 5 days of Day 1.

Sponsors & Collaborators

• Atridia Pty Ltd.: lead

Study Sites (1)

Atridia Pty Limited

Sydney, New South Wales, 2000, Australia

Location

MeSH Terms

Conditions

Gout; Hyperuricemia

Interventions

ruzinurad

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Crystal Arthropathies; Rheumatic Diseases; Purine-Pyrimidine Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Sam Salman, B.Sc.BMBS

  Linear Clinical Research

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 27, 2017
• First Posted: July 7, 2017
• Study Start: July 4, 2017
• Primary Completion: February 15, 2018
• Study Completion: February 15, 2018
• Last Updated: March 21, 2018

Record last verified: 2018-03

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)