A Study to Evaluate the Safety, Tolerability and Pharmaco... | NCT07324434

Name	Class
Xiangbei Welman Pharmaceutical Co., Ltd	INDUSTRY
Guangzhou Xin-Chuangyi Biopharmaceutical Co., Ltd.	UNKNOWN

Description Module

Detailed Description

Part 1: Approximately 39 subjects will be enrolled, 6 groups A1-A6 are predefined (A1 will enroll 3 subjects and A2&A6 will enroll 6 subjects, A3 A4 A5 will enroll 8 subjects). The planned dose escalation of F-02-2-Na will include 6-ascending single-dose cohorts with tentative PO doses ranging from 0.5 mg to 60 mg. Subjects in each SAD cohort will be randomly assigned to receive active drug or matching placebo in a 2:1 or 3:1 ratio (n=2 or 4 or 6 subjects to receive F-02-2-Na, n=1 or 2 subjects will be administered placebo).Safety and PKPD assessments will continue for 72 hours post dose, with discharge from the Phase I Clinical Research Center following completion of all 72-hour procedures on Day 4. Subjects will receive a phone call for an End-of-Study (EOS) follow-up on Day 7 (±1 day).In SAD A4 (20 mg), collected blood, urine, and feces will be used for the mass balance study.
Part 2: Approximately 30 subjects will be enrolled.Three dose groups (B1~B3) are predefined, with 10 subjects per group (including 2 subjects receiving placebo). The administration doses are 25 mg, 50 mg, and 100 mg respectively, administered once daily for 7 consecutive days (a total of 7 administrations).After subjects complete the collection of pharmacokinetic and pharmacokinetics blood & urine samples at 72.0 hours post-administration and undergo relevant examinations, they may leave the Phase I Clinical Research Center upon completion of all tests .

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
A1-0.5 mg T	Experimental	The intervention consists of a single oral administration of F-02-2-Na (0.5 mg). The study drug is administered in a fasting state (at least 10 hours), and subjects will be continuously monitored for 72 hours following administration in Safety and PKPD assessments.	Drug: F-02-2-Na Tablet (0.5 mg)
A1-0.5 mg R	Placebo Comparator	The intervention consists of a single oral administration of matching placebo (0.5 mg). The administration conditions are the same as those for the experimental arm	Drug: F-02-2-Na Matching Placebo (0.5 mg)
A2-5 mg-T	Experimental	The intervention consists of a single oral administration of F-02-2-Na (5 mg). The study drug is administered in a fasting state (at least 10 hours), and subjects will be continuously monitored for 72 hours following administration in Safety and PKPD assessments	Drug: F-02-2-Na Tablet (5 mg)
A2-5 mg-R	Placebo Comparator	The intervention consists of a single oral administration of matching placebo (5 mg). The administration conditions are the same as those for the experimental arm.	Drug: F-02-2-Na Matching Placebo (5 mg)
A3-10 mg-T	Experimental

Interventions

Name	Type	Description	Arm Group Labels	Other Names
F-02-2-Na Tablet (0.5 mg)	Drug	The intervention involves the single oral administration of F-02-2-Na tablets at a dose of 0.5 mg, given once in a fasting state (after at least 10 hours of fasting). The drug is formulated as film-coated tablets with a strength of 1 mg per tablet, manufactured by Guangdong Hengqin Novagains Biopharmaceutical Co., Ltd. (batch number: 250901). Safety and PKPD parameters will be continuously monitored for 72 hours following administration.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Safety and tolerability: Adverse Events (AEs) of ascending single and multiple oral doses of F-02-2-Na in adult subjects.	Incidence, severity, and seriousness of adverse events (AEs) following ascending single and multiple oral doses of F-02-2-Na in adult subjects.	0-72 hours post dose
Safety and Tolerability: Concomitant Medications of ascending single and multiple oral doses in Adult Subjects	Proportion of adult Subjects Using Concomitant Medications During Treatment during treatment with ascending single and multiple oral doses of F-02-2-Na.	0-72 hours post dose
Safety and Tolerability: Electrocardiogram (ECG) Findings ascending single and multiple oral doses of F-02-2-Na in Adult Subjects	Proportion of adult subjects with abnormal findings in electrocardiogram (ECG) parameters (including PR interval, QRS duration, QT/QTc interval, heart rate, and rhythm) following ascending single and multiple oral doses of F-02-2-Na.	From pre-dose (baseline) to 72 hours after the last dose.
Proportion of subjects with abnormal hematology findings following ascending single and multiple oral doses of F-02-2-Na.	Proportion of subjects with clinically significant abnormalities in hematology parameters (e.g., hemoglobin, hematocrit, red blood cell count, white blood cell count with differential, platelet count).	From pre-dose (baseline) to 72 hours after the last dose.
Proportion of subjects with abnormal coagulation findings following ascending single and multiple oral doses of F-02-2-Na.	Proportion of adult subjects with clinically significant abnormalities in coagulation parameters (e.g., PT, INR, aPTT).	From pre-dose (baseline) to 72 hours after the last dose.

Secondary Outcomes

Measure	Description	Time Frame
Mass Balance: Total Renal Excretion Amount of F-02-2-Na in Healthy Adult Subjects	Total amount of F-02-2-Na excreted via the renal route (expressed as absolute amount or percentage of administered dose), estimated from urinary drug concentrations in healthy adult subjects.	From pre-dose (baseline) to 72 hours post dose.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

For Healthy Adult Subjects
1.The subjects should fully understand the purpose, nature, process of the study and the possible adverse reactions, voluntarily act as subjects, and sign the informed consent form before the start of any research procedures.
2.Healthy male or female subjects aged 18 to 45 years old (inclusive).
3.The body weight for male and female subjects should be ≥ 50.0 kg and ≥ 45.0 kg, respectively; the body mass index (BMI) should be between 19 kg/m² and 26 kg/m² (inclusive).
4.The subjects should have normal results or abnormal results without clinical significance in vital signs check, physical examination, clinical laboratory tests (Complete Blood Count(CBC), urine analysis, blood biochemistry, coagulation panel, free thyroid function tests), chest X-ray, liver and renal color ultrasound and 12-lead electrocardiogram.
5. Normal renal function as determined by Investigator following review of clinical laboratory test results, including eGFR ≥ 90 mL/min/1.73 m².
6. The subjects (including male subjects) should have no plans for having children from screening until 6 months after the last dose and should voluntarily take effective contraceptive measures and have no plans for sperm or egg donation.
7. The subjects should be able to communicate well with the researchers and understand and comply with the requirements of this study.
For Adult Subjects with Hyperuricemia
1. The subjects should fully understand the purpose, nature, process of the study and the possible adverse reactions, voluntarily act as subjects, and sign the informed consent form before the start of any research procedures.
2. Male or female subjects aged 18 to 45 years (inclusive).
3. Body weight ≥ 50.0 kg for males and ≥ 45.0 kg for females; Body Mass Index (BMI) between 18 kg/m² and 28 kg/m² (inclusive).
4. Subjects with results from vital signs check, physical examination, clinical laboratory tests (except for serum uric acid), chest X-ray, liver ultrasonography, renal ultrasonography, and 12-lead electrocardiogram that show no abnormalities or only abnormalities of no clinical significance.
5. Estimated Glomerular Filtration Rate (eGFR) > 90 mL/min/1.73m² (calculated using the CKD-EPI Creatinine Equation).
6. The subjects (including male subjects) should have no plans for having children from screening until 6 months after the last dose and should voluntarily take effective contraceptive measures and have no plans for sperm or ova donation.
7. Does not meet the 2015 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) Gout Classification Criteria; however, two fasting serum uric acid levels during the screening period are both ≥ 540 μmol/L (as determined by the study center's test results), and the investigator deems the subject in need of long-term uric acid-lowering therapy.

Exclusion Criteria:

1. Subjects with a specific allergic history (such as asthma, urticaria, eczema, etc.) or those with an allergic constitution (such as those known to be allergic to two or more substances), or those with a known history of allergy to F-02-2-Na and related excipients (ascertained through inquiry).
2. Subjects who have had an acute illness within two weeks before the first drug administration (ascertained through inquiry).
3. Subjects with diseases of important organs or systems (including but not limited to liver, kidney, nervous system, blood, endocrine system, lungs, immune system, mental health, cardiovascular and cerebrovascular system, gastrointestinal tract, skin, metabolism, bone and joints, etc.) that are considered clinically significant by the researcher, or those with a history of such serious diseases; or those with a history of tumor (ascertained through inquiry).
4. Subjects with a history of gastrointestinal, liver, kidney, and thyroid diseases that can affect drug absorption or metabolism (ascertained through inquiry).
5. Subjects with a history of gout (ascertained through inquiry).
6. Subjects who have used any medications (including any prescription drugs, over-the-counter drugs, traditional Chinese herbal medicines) and health products within two weeks before the first drug administration (ascertained through inquiry).
7. Subjects who have used any mercaptopurine hydrate or thiopurine drugs within four weeks before the study (ascertained through inquiry).
8. Subjects who have heavily consumed, within 2 weeks prior to the first dose, or ingested within 48 hours prior to dosing, beverages containing caffeine or alcohol, or foods known to affect drug metabolism (such as chocolate, pitaya, mango, pomelo, carambola, guava, orange, grapefruit, or grapefruit products).(ascertained through inquiry)
9. Subjects who have undergone major surgical procedures (excluding diagnostic surgical procedures) within six months before the study , or those who plan to have surgery during the research period, or those who have undergone surgeries that, in the judgment of the researcher, can affect drug absorption, distribution, metabolism, and excretion (ascertained through inquiry).
10. Subjects who have received vaccination within three months before the study (ascertained through inquiry).
11. Subjects who have participated in any other clinical trial within 3 months prior to the current study. (Note: The end date is defined as the date of completion/exit from the previous clinical trial.) (ascertained through inquiry).
12. Subjects who have donated blood within three months before the study, or those whose total blood loss due to blood donation or other reasons has reached or exceeded 400 mL within six months (ascertained through inquiry).
13. Subjects who, on average, consumed more than 14 units of alcohol per week over the past year, or those unable to abstain from alcohol during the study period, or individuals with a breath alcohol test result greater than 0.0 mg/100 mL (ascertained through inquiry/examination).
14. Subjects who smoke more than 5 cigarettes per day on average within three months before the study, or those who cannot stop using any tobacco products during the study (ascertained through inquiry).
15. Subjects with a history of drug abuse (including the repeated and excessive use of various narcotic drugs and psychotropic substances for non-medical purposes) or positive results in drug abuse screening (including morphine, methamphetamine, ketamine, MDMA (3,4-methylenedioxymethamphetamine), cannabis (tetrahydrocannabinolic acid), etc.) within the past year (ascertained through inquiry and examination).
16. Subjects with a positive result in any item of the infectious disease examination during the screening period (including hepatitis B surface antigen, hepatitis C antibody, human immunodeficiency virus antibody, and treponema pallidum antibody) (examination).
17. Subjects who cannot tolerate venipuncture/indwelling needle or those with a history of fainting at the sight of needles or blood (ascertained through inquiry).
18. Subjects with difficult venous blood collection (ascertained through inquiry).
19. Subjects with lactose intolerance (ascertained through inquiry). 20. Subjects with special dietary requirements and who cannot accept the unified diet (ascertained through inquiry).
21. Subjects with dysphagia (ascertained through inquiry).
22. Other subjects are deemed unsuitable for participation by the researcher.
23. In addition to the above requirements, female subjects who meet the following conditions should also be excluded:
a. Those who have used oral contraceptives within 30 days before the study ( ascertained through inquiry ) .
b. Those who have used long-acting estrogen or progesterone injections ( including progesterone-containing intrauterine contraceptive devices ) or implanted tablets within 6 months before the study (ascertained through inquiry ) .
c. Those who have unprotected sexual intercourse with their partners within 14 days before the study ( ascertained through inquiry ) .
d. Those with a positive blood pregnancy test result ( examination ) .
e. Pregnant or lactating women ( ascertained through inquiry ) .

Name	Affiliation	Role
Junyan Wu, MS	Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University	Principal Investigator
Donghui Zheng, MM	Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University	Principal Investigator

PubMed Identifier	Type	Citation	Retractions
31056705	Background	Lee HA, Yu KS, Park SI, Yoon S, Onohara M, Ahn Y, Lee H. URC102, a potent and selective inhibitor of hURAT1, reduced serum uric acid in healthy volunteers. Rheumatology (Oxford). 2019 Nov 1;58(11):1976-1984. doi: 10.1093/rheumatology/kez140.
29688628	Background	Hall J, Gillen M, Yang X, Shen Z. Pharmacokinetics, Pharmacodynamics, and Tolerability of Concomitant Administration of Verinurad and Febuxostat in Healthy Male Volunteers. Clin Pharmacol Drug Dev. 2019 Feb;8(2):179-187. doi: 10.1002/cpdd.463. Epub 2018 Apr 24.