A Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Multiple Doses of SHR4640 in Male Subjects With High Serum Uric Acid Level
Overview
- Phase
- Phase 1
- Intervention
- SHR4640
- Conditions
- Gout
- Sponsor
- Atridia Pty Ltd.
- Enrollment
- 24
- Locations
- 1
- Primary Endpoint
- Incidence of Adverse events in terms of changes in Biochemistry (fasting)
- Status
- Completed
- Last Updated
- 8 years ago
Overview
Brief Summary
This is a single-Center, randomized, double-Blind, placebo-controlled, multiple ascending-dose Phase I trail.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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.
Exclusion Criteria
- •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
- •Has unsuitable venous for blood sampling.
Arms & Interventions
SHR4640 2.5mg
6 subjects assigned to 2.5mg SHR4640 and 2 subjects assigned to placebo
Intervention: SHR4640
SHR4640 10mg
6 subjects assigned to 10mg SHR4640 and 2 subjects assigned to placebo
Intervention: SHR4640
SHR4640 20mg
6 subjects assigned to 20mg SHR4640 and 2 subjects assigned to placebo
Intervention: SHR4640
Outcomes
Primary Outcomes
Incidence of Adverse events in terms of changes in Biochemistry (fasting)
Time Frame: Up to Day 14
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
Incidence of Adverse events in terms of changes in Physical examinations
Time Frame: Up to Day 14
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
Incidence of Adverse events in terms of changes in Vital signs
Time Frame: Up to Day 14
Oral temperature, respiratory rate, blood pressure, and pulse rate
Incidence of Adverse events in terms of changes in 12-lead ECGs
Time Frame: Up to Day 14
The 12-lead ECGs must be recorded after the subjects have rested in the supine position for 5 minutes to ensure a stable baseline.
Incidence of Adverse events in terms of changes in Hematology
Time Frame: Up to Day 14
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
Incidence of Adverse events in terms of changes in Urinalysis
Time Frame: Up to Day 14
Urobilinogen Dipstick urinalysis, including: pH, Specific gravity, Protein, Blood, Leukocytes, Glucose, Ketones, Bilirubin, Nitrites
Secondary Outcomes
- 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)
- Changes in urinary uric acid excretion from baseline(Up to Day 10)