Clinical trial NCT03211403: Multiple Doses Study of SHR4640 in Male Subjects With High Serum Uric Acid Level
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Gout
Hyperuricemia
Lead sponsor: Atridia Pty Ltd.
Sponsor class: INDUSTRY
First posted: 2017-07-07
Enrollment: 24
Sex: MALE
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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


Eligibility criteria: Inclusion Criteria:

1. Male, aged between 18 and 65 years, inclusive.
2. Body weight ≥ 50 kg and body mass index between 18.0 and 35.0 kg/m2, inclusive.
3. Screening sUA level ≥0.36 mmol/L.
4. 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.
5. 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.
6. Negative drug screen (including alcohol) at screening and on admission to clinical site.
7. 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:

1. History of hypersensitivity to SHR4640 or its analogues.
2. History of gout.
3. Screening alanine aminotransferase, aspartate aminotransferase, total bilirubin, or gamma glutamyl transferase \> 1.5 × upper limit of normal.
4. Positive result for human immunodeficiency virus (HIV).
5. Positive result for hepatitis B surface antigen or hepatitis C virus antibody.
6. History or presence of kidney stones.
7. 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.
8. Undergone major surgery within 3 months of Day 1 or has surgery planned during study participation.
9. Donated any blood or plasma in the past month or more than 400 mL within 3 months of Day 1.
10. Has unsuitable venous for blood sampling.
11. Use of tobacco products within 30 days of Day 1.
12. Heavy caffeine drinker (more than 5 cups or glasses of caffeinated beverages per day).
13. History of drug and/or alcohol abuse in the last year.
14. 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).
15. Consumes grapefruit and/or poppy seed within 5 days of Day 1.
16. Unable to refrain from strenuous exercises, tobacco products, alcohol, grapefruit, and/or poppy seed from Day -2 to Day 10.
17. Use of any of the following, unless agreed as nonclinically relevant by the Investigator and the Sponsor:

1) Prescription medication within 2 weeks of Day 1. 2) Over-the-counter medication within 1 week of Day 1. 3) Use of any over the-counter, nutraceuticals, or prescription medications that might interfere with the absorption, distribution, metabolism, or excretion of SHR4640 (proton-pump inhibitor, fluconazole, indomethacin, ranitidine, flurbiprofen, probenecid, aprepitant, etc.) within 1 month of Day 1.

18. Received the last dose of a study drug (or treatment with a medical device) within 30 days or 5 T1/2 (whichever is longer) of the study drug of Day 1 or are currently participating in another study of a study drug (or medical device).

19. Any other medical or psychological condition, which in the opinion of the Investigator, might create undue risk to the subject or interfere with the subject's ability to comply with the protocol requirements or to complete the study.

Primary outcomes:
measure: Incidence of Adverse events in terms of changes in Hematology
timeFrame: Up to Day 14
measure: Incidence of Adverse events in terms of changes in Urinalysis
timeFrame: Up to Day 14
measure: Incidence of Adverse events in terms of changes in Biochemistry (fasting)
timeFrame: Up to Day 14
measure: Incidence of Adverse events in terms of changes in Physical examinations
timeFrame: Up to Day 14
measure: Incidence of Adverse events in terms of changes in Vital signs
timeFrame: Up to Day 14
measure: Incidence of Adverse events in terms of changes in 12-lead ECGs
timeFrame: Up to Day 14
Secondary outcomes:
measure: Peak Plasma Concentration (Cmax) (of single dose and at stable status)
timeFrame: Up to Day 10
measure: Area under the plasma concentration versus time curve (AUC) (of single dose and at stable status)
timeFrame: Up to Day 10
measure: Half-time (T1/2) (of single dose and at stable status)
timeFrame: Up to Day 10
measure: Time to the peak plasma concentration (Tmax) (of single dose and at stable status)
timeFrame: Up to Day 10
measure: Changes in serum uric acid concentration from baseline
timeFrame: Up to Day 10
measure: Changes in urinary uric acid excretion from baseline
timeFrame: Up to Day 10
Other outcomes:
Locations:
city: Sydney
country: Australia
facility: Atridia Pty Limited
state: New South Wales
Study officials:
affiliation: Linear Clinical Research
name: Sam Salman, B.Sc.BMBS
role: PRINCIPAL_INVESTIGATOR
References: