Safety, Tolerability, and Pharmacokinetics of FHND1002 Granules in Healthy Adults

A Phase I Clinical Study to Evaluate the Safety, Tolerability, and Pharmacokinetic Characteristics of FHND1002 Granules After Single and Multiple Doses in Healthy Adult Volunteers

The goal of this clinical trial is to evaluate the safety, tolerability, and pharmacokinetic (PK) profile of FHND1002 granules in healthy adult volunteers. The study will also assess how a high-fat meal affects the PK characteristics of FHND1002.

The main questions this study aims to answer are:

What are the safety and tolerability of FHND1002 granules when administered as single or multiple doses? What are the PK parameters of FHND1002, and what metabolites can be identified in humans?

Participants will:

Take FHND1002 granules or a placebo once daily, either as a single dose or for 7 consecutive days.

Attend regular clinic visits for checkups, tests, and blood sample collection. Undergo assessments, including monitoring for adverse events, physical exams, vital signs, ECGs, and laboratory tests.

This study aims to evaluate the safety, tolerability, and pharmacokinetic (PK) profile of FHND1002 granules in healthy adult volunteers. The study is divided into two parts: a single ascending dose (SAD) phase and a multiple ascending dose (MAD) phase, with an additional evaluation of the effect of a high-fat meal on the PK characteristics of FHND1002.

The primary objectives of this study are:

To assess the safety and tolerability of FHND1002 granules following single and multiple doses in healthy volunteers.

To evaluate the impact of a high-fat meal on the PK profile of FHND1002 granules after a single oral dose.

The secondary objectives include:

To characterize the pharmacokinetic parameters of FHND1002 granules in healthy volunteers.

To identify and conduct preliminary research on drug metabolites in humans. This single-center, randomized, double-blind, placebo-controlled, single and multiple ascending dose Phase I clinical trial involves healthy adult volunteers. Based on preclinical pharmacodynamic, pharmacokinetic, and toxicological studies, as well as the formulation specifications of FHND1002 (25 mg and 100 mg), the maximum recommended starting dose for humans is set at 50 mg.

In the SAD phase, five dose groups (50 mg, 100 mg, 150 mg, 200 mg, and 250 mg) will be included, with 8 participants in each group (6 receiving FHND1002 and 2 receiving a placebo). Additionally, a food effect cohort (100 mg) will include 16 participants (14 receiving FHND1002 and 2 receiving a placebo), split into two groups to evaluate the impact of food under fasting and postprandial conditions.

In the MAD phase, three dose groups (100 mg, 150 mg, and 200 mg) will be included, with 8 participants per group (6 receiving FHND1002 and 2 receiving a placebo). Participants will receive FHND1002 or placebo once daily under fasting conditions for 7 consecutive days.

Throughout the study, participants will undergo regular assessments, including blood sample collection for PK analysis, adverse event (AE) monitoring, and evaluations such as physical exams, vital signs, ECGs, and laboratory tests. This study is expected to provide important data on the safety, tolerability, and pharmacokinetics of FHND1002, contributing to its further clinical development.

Inclusion Criteria:

• Aged ≥18 and ≤45 years, regardless of gender.
• Male volunteers weigh ≥50 kg, and female volunteers weigh ≥45 kg, with a body mass index (BMI) between 19.0 and 26.0 kg/m² (inclusive).
• Medical history, physical examination, laboratory tests, and other assessments are normal or clinically insignificant, as determined by the investigator.
• Volunteers have no plans for pregnancy and voluntarily agree to use effective non-drug contraceptive measures (e.g., complete abstinence, condoms, sterilization) throughout the study and for three months after the last dose, with no plans for sperm or egg donation.
• Volunteers agree to comply with all study procedures and follow-up schedules and provide written informed consent.

Exclusion Criteria:

• History or presence of gastrointestinal, renal, hepatic, pulmonary, neurological, hematological, endocrine, oncological, immunological, psychiatric, or cardiovascular diseases that, in the investigator's opinion, may affect the safety of the volunteer or study results.
• History of severe allergies (e.g., angioedema or anaphylactic shock), hypersensitivity (e.g., to pollen or two or more drugs/foods), or known allergy to any components or excipients of the investigational drug.
• Use of any drugs that inhibit or induce hepatic drug metabolism (e.g., barbiturates, carbamazepine, phenytoin, corticosteroids) within 28 days before screening.
• Difficulty swallowing or a history of gastrointestinal diseases affecting drug absorption, digestive system surgeries (except for appendectomy, hemorrhoidectomy, or inguinal hernia repair), or known factors affecting pharmacokinetics.
• Underwent surgery within six months prior to screening or had surgery affecting drug absorption, distribution, metabolism, or excretion, as determined to be clinically significant by the investigator; or plans to undergo surgery during the study period.
• History of drug abuse, drug dependence, or a positive drug abuse screening result.
• Use of any prescription drugs, over-the-counter drugs, herbal medicines, or vitamins within 14 days prior to screening or within five half-lives of the drug before the first dose of the study drug (unless deemed irrelevant by the investigator).
• Participation in another clinical trial with drug administration within three months prior to the first dose of the study drug.
• Abnormal results in vital signs, electrocardiograms, ultrasounds, chest X-rays, or laboratory tests (e.g., blood routine, urinalysis, coagulation, blood biochemistry) deemed clinically significant by the investigator.
• Blood donation or other causes of blood loss exceeding 400 mL within three months prior to screening (excluding physiological blood loss in females).
• Difficulty with venous blood collection or a history of needle or blood phobia.
• Frequent alcohol consumption within three months prior to screening (defined as more than 14 units of alcohol per week, where 1 unit = 360 mL of beer, 45 mL of spirits with 40% alcohol, or 150 mL of wine), a positive alcohol breath test result, or inability to abstain from alcohol during the study.
• Vaccination within one month prior to the first dose or planned vaccination during the study or within one month after the study.
• Smoking more than five cigarettes per day within three months prior to screening or inability to abstain from tobacco use during the study.
• Excessive consumption of tea, coffee, or caffeine-containing beverages (more than 8 cups per day, where 1 cup = 250 mL) within three months prior to screening, consumption of specific foods (e.g., dragon fruit, mango, grapefruit) within 14 days prior to screening, or unwillingness to avoid caffeine-containing foods and beverages (e.g., tea, coffee, chocolate, cocoa), grapefruit products, or strenuous activities that may affect drug absorption, metabolism, or excretion during the study.
• Positive serological results for HBsAg, anti-HCV, anti-HIV, or TP-Ab at screening.
• Pregnant or breastfeeding female volunteers, or positive serum pregnancy test results.
• Male volunteers (or their partners) or female volunteers with plans for conception during the study period or within three months after study completion, or unwillingness to use non-drug contraceptive measures (e.g., complete abstinence, condoms, sterilization) during the study.
• Volunteers with specific dietary requirements (e.g., lactose intolerance) or unwillingness to adhere to the standardized diet provided during the study.
• Any other condition or factor that, in the investigator's judgment, renders the volunteer unsuitable for participation in the clinical trial.