A Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Oral F-02-2-Na Tablets in Adult Subjects

Guangdong Hengqin Novagains Biopharmaceutical Co., Ltd.

Status and phase: Invitation-only; Phase 1

Conditions: Hyperuricemia With or Without Gout

Treatments: Drug: F-02-2-Na Tablet (25mg); Drug: F-02-2-Na Matching Placebo (0.5mg); Drug: F-02-2-Na Tablet (200 mg); Drug: F-02-2-Na Matching Placebo (5mg); Drug: F-02-2-Na Matching Placebo (100mg) -Multiple dose; Drug: F-02-2-Na Matching Placebo (25mg) -Multiple dose; Drug: F-02-2-Na Tablet (150 mg); Drug: F-02-2-Na Tablet (50mg)-Multiple dose; Drug: F-02-2-Na Matching Placebo (200 mg); Drug: F-02-2-Na Matching Placebo (150 mg); Drug: F-02-2-Na Tablet (100mg)-Multiple dose; Drug: F-02-2-Na Tablet (75mg); Drug: F-02-2-Na Matching Placebo (75mg); Drug: F-02-2-Na Tablet (5mg); Drug: F-02-2-Na Tablet (25mg)-Multiple dose; Drug: F-02-2-Na Matching Placebo (50mg) -Multiple dose; Drug: F-02-2-Na Matching Placebo (25mg); Drug: F-02-2-Na Tablet (0.5 mg)

Study type: Interventional

Funder types: Industry; Other

Identifiers

NCT07324434

F-02-2-Na-2025-PROT-I-1

Details and patient eligibility

About

The primary objective of this study is to evaluate the safety, tolerability and pharmacokinetic (PK) profiles of ascending single orally administered doses of F-02-2-Na in adult subjects (to include the Mass Balance) & multiple orally administered doses of F-02-2-Na in adult subjects with Hyperuricemia.

Full 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, A3A4A5 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 200 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 A3 (25 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 .

Enrollment: 69 estimated patients

Sex: All

Ages: 18 to 45 years old

Volunteers: Accepts Healthy Volunteers

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 ) .

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

69 participants in 18 patient groups, including a placebo group

A1-0.5mg T

Experimental group

Description:

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.

Treatment:

Drug: F-02-2-Na Tablet (0.5 mg)

A1-0.5mg R

Placebo Comparator group

Description:

The intervention consists of a single oral administration of matching placebo (0.5mg). The administration conditions are the same as those for the experimental arm

Treatment:

Drug: F-02-2-Na Matching Placebo (0.5mg)

A2-5mg-T

Experimental group

Description:

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

Treatment:

Drug: F-02-2-Na Tablet (5mg)

A2-5mg-R

Placebo Comparator group

Description:

The intervention consists of a single oral administration of matching placebo (5mg). The administration conditions are the same as those for the experimental arm.

Treatment:

Drug: F-02-2-Na Matching Placebo (5mg)

A3-25mg-T

Experimental group

Description:

The intervention consists of a single oral administration of F-02-2-Na (25 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.

Treatment:

Drug: F-02-2-Na Tablet (25mg)

A3-25mg-R

Placebo Comparator group

Description:

The intervention consists of a single oral administration of matching placebo (25mg). The administration conditions are the same as those for the experimental arm.

Treatment:

Drug: F-02-2-Na Matching Placebo (25mg)

A4-75mg-T

Experimental group

Description:

The intervention consists of a single oral administration of F-02-2-Na (75 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.

Treatment:

Drug: F-02-2-Na Tablet (75mg)

A4-75mg-R

Placebo Comparator group

Description:

The intervention consists of a single oral administration of matching placebo (75mg). The administration conditions are the same as those for the experimental arm.

Treatment:

Drug: F-02-2-Na Matching Placebo (75mg)

A5-150mg-T

Experimental group

Description:

The intervention consists of a single oral administration of F-02-2-Na (150 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

Treatment:

Drug: F-02-2-Na Tablet (150 mg)

A5-150mg-R

Placebo Comparator group

Description:

The intervention consists of a single oral administration of matching placebo (150mg). The administration conditions are the same as those for the experimental arm.

Treatment:

Drug: F-02-2-Na Matching Placebo (150 mg)

A6-200mg-T

Experimental group

Description:

The intervention consists of a single oral administration of F-02-2-Na (200 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.

Treatment:

Drug: F-02-2-Na Tablet (200 mg)

A6-200mg-R

Placebo Comparator group

Description:

The intervention consists of a single oral administration of matching placebo (200mg). The administration conditions are the same as those for the experimental arm.

Treatment:

Drug: F-02-2-Na Matching Placebo (200 mg)

B1-25mg-T

Experimental group

Description:

The intervention consists of the multiple oral administrations of F-02-2-Na tablets at a dose of 25mg for 7 consecutive days.

Treatment:

Drug: F-02-2-Na Tablet (25mg)-Multiple dose

B1-25mg-R

Placebo Comparator group

Description:

The intervention consists of the multiple oral administrations of matching placebo (25mg). The administration conditions are the same as those for the experimental arm.

Treatment:

Drug: F-02-2-Na Matching Placebo (25mg) -Multiple dose

B2-50mg-T

Experimental group

Description:

The intervention consists of the multiple oral administrations of F-02-2-Na tablets at a dose of 50mg for 7 consecutive days.

Treatment:

Drug: F-02-2-Na Tablet (50mg)-Multiple dose

B2-50mg-R

Placebo Comparator group

Description:

The intervention consists of the multiple oral administrations of matching placebo (50mg). The administration conditions are the same as those for the experimental arm.

Treatment:

Drug: F-02-2-Na Matching Placebo (50mg) -Multiple dose

B3-100mg-T

Experimental group

Description:

The intervention consists of the multiple oral administrations of F-02-2-Na tablets at a dose of 100mg for 7 consecutive days.

Treatment:

Drug: F-02-2-Na Matching Placebo (100mg) -Multiple dose

B3-100mg-R

Placebo Comparator group

Description:

The intervention consists of the multiple oral administrations of matching placebo (100mg). The administration conditions are the same as those for the experimental arm.

Treatment:

Drug: F-02-2-Na Tablet (100mg)-Multiple dose