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

Official title

A Randomized, Double-Blind, Placebo-Controlled, Phase 1 Study of Oral F-02-2-Na Tablets in Adult Subjects: Assessment of the Safety and Pharmacokinetics of Single Ascending Doses (to Include the Mass Balance) & Multiple Ascending Doses

Overview

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.

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 .

Interventions

• Drug F-02-2-Na Tablet (0.5 mg)
  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.
• Drug F-02-2-Na Matching Placebo (0.5 mg)
  The intervention consists of the single oral administration of a matching placebo (0.5 mg) for F-02-2-Na. Formulated as film-coated tablets (consistent with F-02-2-Na in appearance, color, and strength), the placebo contains no F-02-2-Na or other pharmacologically active ingredients and is manufactured by Guangdong Hengqin Novagains Biopharmaceutical Co., Ltd. (batch number: 250101). The administration conditions are identical to those of the experimental arm in this study; however, it has no th
• Drug F-02-2-Na Tablet (5 mg)
  The intervention involves the single oral administration of F-02-2-Na tablets at a dose of 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 5mg per tablet, manufactured by Guangdong Hengqin Novagains Biopharmaceutical Co., Ltd. (batch number: 250101). Safety and PKPD parameters will be continuously monitored for 72 hours following administration.
• Drug F-02-2-Na Matching Placebo (5 mg)
  The intervention consists of the single oral administration of a matching placebo (5 mg) for F-02-2-Na. Formulated as film-coated tablets (consistent with F-02-2-Na in appearance, color, and strength), the placebo contains no F-02-2-Na or other pharmacologically active ingredients and is manufactured by Guangdong Hengqin Novagains Biopharmaceutical Co., Ltd. (batch number: 250101). The administration conditions are identical to those of the experimental arm in this study; however, it has no ther
• Drug F-02-2-Na Tablet (10 mg)
  The intervention involves the single oral administration of F-02-2-Na tablets at a dose of 10 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 10 mg per tablet, manufactured by Guangdong Hengqin Novagains Biopharmaceutical Co., Ltd. (batch number: 250101). Safety and PKPD parameters will be continuously monitored for 72 hours following administration. In SAD A3 (10 mg), collected blood, urine, and feces will
• Drug F-02-2-Na Matching Placebo (10 mg)
  The intervention consists of the single oral administration of a matching placebo (10 mg) for F-02-2-Na. Formulated as film-coated tablets (consistent with F-02-2-Na in appearance, color, and strength), the placebo contains no F-02-2-Na or other pharmacologically active ingredients and is manufactured by Guangdong Hengqin Novagains Biopharmaceutical Co., Ltd. (batch number: 250101). The administration conditions are identical to those of the experimental arm in this study; however, it has no the
• Drug F-02-2-Na Tablet (20 mg)
  The intervention involves the single oral administration of F-02-2-Na tablets at a dose of 20 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 10 mg per tablet, manufactured by Guangdong Hengqin Novagains Biopharmaceutical Co., Ltd. (batch number: 250101). Safety and PKPD parameters will be continuously monitored for 72 hours following administration.
• Drug F-02-2-Na Matching Placebo (20 mg)
  The intervention consists of the single oral administration of a matching placebo (20 mg) for F-02-2-Na. Formulated as film-coated tablets (consistent with F-02-2-Na in appearance, color, and strength), the placebo contains no F-02-2-Na or other pharmacologically active ingredients and is manufactured by Guangdong Hengqin Novagains Biopharmaceutical Co., Ltd. (batch number: 250101). The administration conditions are identical to those of the experimental arm in this study; however, it has no the
• Drug F-02-2-Na Tablet (40 mg)
  The intervention involves the single oral administration of F-02-2-Na tablets at a dose of 40 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 10mg per tablet, manufactured by Guangdong Hengqin Novagains Biopharmaceutical Co., Ltd. (batch number: 250101). Safety and PKPD parameters will be continuously monitored for 72 hours following administration.
• Drug F-02-2-Na Matching Placebo (40 mg)
  The intervention consists of the single oral administration of a matching placebo (40 mg) for F-02-2-Na. Formulated as film-coated tablets (consistent with F-02-2-Na in appearance, color, and strength), the placebo contains no F-02-2-Na or other pharmacologically active ingredients and is manufactured by Guangdong Hengqin Novagains Biopharmaceutical Co., Ltd. (batch number: 250101). The administration conditions are identical to those of the experimental arm in this study; however, it has no the

Primary outcome measures

• Safety and tolerability: Adverse Events (AEs) of ascending single and multiple oral doses of F-02-2-Na in adult subjects. [Time frame: 0-72 hours post dose]
• Safety and Tolerability: Concomitant Medications of ascending single and multiple oral doses in Adult Subjects [Time frame: 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 [Time frame: 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. [Time frame: 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. [Time frame: From pre-dose (baseline) to 72 hours after the last dose.]
• Proportion of subjects with abnormal urinalysis findings following ascending single and multiple oral doses of F-02-2-Na. [Time frame: From pre-dose (baseline) to 72 hours after the last dose.]
• Proportion of subjects with abnormal clinical chemistry findings following ascending single and multiple oral doses of F-02-2-Na [Time frame: pre-dose (baseline) to 72 hours after the last dose]
• Proportion of subjects with abnormal renal morphology following administration of F-02-2-Na [Time frame: From pre-dose (baseline) to 72 hours after the last dose]
• Proportion of subjects with abnormal pelvicalyceal system findings following administration of F-02-2-Na [Time frame: From pre-dose (baseline) to 72 hours post dose]
• Proportion of subjects with abnormal renal vascular hemodynamics following administration of F-02-2-Na [Time frame: From pre-dose (baseline) to 72 hours post dose]

Secondary outcome measures (11)

• Mass Balance: Total Renal Excretion Amount of F-02-2-Na in Healthy Adult Subjects [Time frame: From pre-dose (baseline) to 72 hours post dose.]
• Mass Balance: Fecal Excretion Rate of F-02-2-Na in Healthy Adult Subjects [Time frame: From pre-dose (baseline) to 72 hours post dose.]
• Mass Balance: Total Fecal Excretion Amount of F-02-2-Na in Healthy Adult Subjects [Time frame: From pre-dose (baseline) to 72 hours post dose.]
• Explore the dose-exposure-effect relationship：Correlation between Exposure Parameters of F-02-2-Na and Serum Uric Acid (sUA) Reduction in Adult Subjects [Time frame: From pre-dose (baseline) to 72 hours after the last dose.]
• Exploration of Potential Biomarkers Associated with the Pharmacodynamics of F-02-2-Na in Adult Subjects [Time frame: From pre-dose (baseline) to 72 hours after the last dose.]
• Absolute Change in Serum Uric Acid (sUA) Levels in Adult Subjects After Single and Multiple Oral Administrations of F-02-2-Na [Time frame: From pre-dose (baseline) to 72 hours after the last dose.]
• Percentage Change in Serum Uric Acid (sUA) Levels in Adult Subjects After Single and Multiple Oral Administrations of F-02-2-Na [Time frame: From pre-dose (baseline) to 72 hours after the last dose.]
• Uric Acid Excretion (AeUR) in Adult Subjects After Single and Multiple Oral Administrations of F-02-2-Na [Time frame: From pre-dose (baseline) to 72 hours after the last dose.]
• Uric Acid Clearance Rate (CLUR) in Adult Subjects After Single and Multiple Oral Administrations of F-02-2-Na [Time frame: From pre-dose (baseline) to 72 hours after the last dose.]
• Area Under the Curve (AUC) of Serum Uric Acid (sUA) Dynamic Change Curve in Adult Subjects After Single and Multiple Oral Administrations of F-02-2-Na [Time frame: From pre-dose (baseline) to 72 hours after the last dose.]
• Total 24-Hour Uric Acid Excretion in Adult Subjects After Single and Multiple Oral Administrations of F-02-2-Na [Time frame: From pre-dose (baseline) to 72 hours after the last dose.]

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 ) .

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

China · 1 center

• Sun Yat-sen Memorial Hospital, Sun Yat-sen University — Guangzhou

Publications

• 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. PMID 31056705
• 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. PMID 29688628
• Ding R, Chen L, Li X, Xiong T, Chen H, Hu X, Li Y, Zhou Y, Liu K, Wu J, Jiang F, Peng Q. A Phase I Study to Evaluate the Pharmacokinetic Drug-Drug Interaction of HP501, Febuxostat, and Colchicine in Male Chinese Patients with Hyperuricemia. Clin Drug Investig. 2023 Jun;43(6):401-411. doi: 10.1007/s40261-023-01274-7. Epub 2023 May 30. PMID 37248357
• Wang Z, Li X, Jin Y, Liu R, Di X, Zhou Y, Wang Y, Fan L, Chen Y, Wang Y, Zheng L. Safety, Efficacy, and Pharmacokinetics of HP501 in Healthy Volunteers and Hyperuricemic Patients: A Phase I/IIa Study. J Clin Endocrinol Metab. 2022 May 17;107(6):1667-1678. doi: 10.1210/clinem/dgac032. PMID 35106590

Identifiers

NCT: NCT07324434 · F-02-2-Na-2025-PROT-I-1

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗