Safety, Tolerability, and Pharmacokinetics of FHND1002 Granules in Healthy Adults (FHND1002-Ⅰ)

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.

Study Overview

• Status: Enrolling by invitation
• Conditions: Amyotrophic Lateral Sclerosis (ALS)
• Intervention / Treatment: Drug: 50mg FHND1002; Drug: 100mg FHND1002; Drug: 150 mg FHND1002; Drug: 200 mg FHND1002（fasting）; Drug: 250mg FHND1002; Drug: 200mg FHND1002(postprandial)

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 72
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Gansu
    • Lanzhou, Gansu, China, 730013
      • The First Hospital of Lanzhou University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single dose; Participants will receive a one-time dose (50 mg, 100 mg, 150 mg, 200 mg, or 250 mg) under fasting conditions or with a high-fat meal (for the 200 mg group).	Drug: 50mg FHND1002; Participants will receive a daily oral dose of FHND1002 granules (50 mg) ,administered in the morning after fasting for at least 10 hours. The dose will be taken with 240 mL of water.; Drug: 100mg FHND1002; Participants will receive a daily oral dose of FHND1002 granules (100 mg) , administered in the morning after fasting for at least 10 hours. The dose will be taken with 240 mL of water.; Drug: 150 mg FHND1002; Participants will receive a daily oral dose of FHND1002 granules (150 mg), administered in the morning after fasting for at least 10 hours. The dose will be taken with 240 mL of water.; Drug: 200 mg FHND1002（fasting）; Participants will receive a daily oral dose of FHND1002 granules (200 mg), administered in the morning after fasting for at least 10 hours. The dose will be taken with 240 mL of water.; Drug: 250mg FHND1002; Participants will receive a daily oral dose of FHND1002 granules (250 mg), administered in the morning after fasting for at least 10 hours. The dose will be taken with 240 mL of water.; Drug: 200mg FHND1002(postprandial); Participants will receive a one-time dose (200 mg) under postprandial conditions
Experimental: Multiple dose; Participants will receive daily doses (100 mg, 150 mg, or 200 mg) for 7 consecutive days under fasting conditions.	Drug: 100mg FHND1002; Participants will receive a daily oral dose of FHND1002 granules (100 mg) , administered in the morning after fasting for at least 10 hours. The dose will be taken with 240 mL of water.; Drug: 150 mg FHND1002; Participants will receive a daily oral dose of FHND1002 granules (150 mg), administered in the morning after fasting for at least 10 hours. The dose will be taken with 240 mL of water.; Drug: 200 mg FHND1002（fasting）; Participants will receive a daily oral dose of FHND1002 granules (200 mg), administered in the morning after fasting for at least 10 hours. The dose will be taken with 240 mL of water.
Placebo Comparator: Placebo; 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.	Drug: 50mg FHND1002; Participants will receive a daily oral dose of FHND1002 granules (50 mg) ,administered in the morning after fasting for at least 10 hours. The dose will be taken with 240 mL of water.; Drug: 100mg FHND1002; Participants will receive a daily oral dose of FHND1002 granules (100 mg) , administered in the morning after fasting for at least 10 hours. The dose will be taken with 240 mL of water.; Drug: 150 mg FHND1002; Participants will receive a daily oral dose of FHND1002 granules (150 mg), administered in the morning after fasting for at least 10 hours. The dose will be taken with 240 mL of water.; Drug: 200 mg FHND1002（fasting）; Participants will receive a daily oral dose of FHND1002 granules (200 mg), administered in the morning after fasting for at least 10 hours. The dose will be taken with 240 mL of water.; Drug: 250mg FHND1002; Participants will receive a daily oral dose of FHND1002 granules (250 mg), administered in the morning after fasting for at least 10 hours. The dose will be taken with 240 mL of water.; Drug: 200mg FHND1002(postprandial); Participants will receive a one-time dose (200 mg) under postprandial conditions

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peak Plasma Concentration (Cmax)	This outcome measures the maximum observed plasma concentration of FHND1002 and its metabolites after single and multiple doses.	4 weeks
Time to Peak Plasma Concentration (Tmax)	This outcome evaluates the time required to reach maximum plasma concentration of FHND1002 and its metabolites.	4 weeks
Area Under the Curve from 0 to the Last Quantifiable Time Point (AUClast)	AUClast means Area Under the Concentration-Time Curve from 0 to the Last Quantifiable Time Point . This outcome assesses the total drug exposure up to the last measurable plasma concentration after single and multiple doses of FHND1002.	4 weeks
Area Under the Curve Over the Dosing Interval (AUCτ)	This outcome evaluates drug exposure during the dosing interval at steady state. τ means the dosing intervals.	4 weeks
Trough Concentration (Cmin)	The parameter is for multiple dose study. This outcome measures the minimum plasma concentration of FHND1002 and its metabolites before the next dose.	4 weeks
Average Plasma Concentration (Cavg)	The parameter is for multiple dose study. This outcome evaluates the average plasma concentration of FHND1002 during the dosing interval at steady state.	4 weeks
Accumulation Ratio (Rac)	Accumulation Ratio (Rac) is for Cmax and AUCτ. The outcome evaluates the accumulation of FHND1002 after multiple doses, calculated as the ratio of steady-state to single-dose parameters (e.g., Rac_Cmax, Rac_AUCτ).	4 weeks
Elimination Half-life (t1/2)	Elimination Half-life (t1/2) of FHND1002 assesses the time required for the plasma concentration of FHND1002 to decrease by half during the elimination phase.	4 weeks
Area Under the Curve from 0 to Infinity (AUC0-inf)	This outcome evaluates the total drug exposure from the time of dosing extrapolated to infinity for FHND1002 and its metabolites.	4 weeks
Incidence of Adverse Events(AEs)	This endpoint evaluates the safety of FHND1002 by monitoring the incidence of adverse events (AEs)	7 weeks
Incidence of Adverse Drug Reactions (ADRs)	This endpoint evaluates the safety of FHND1002 by monitoring the incidence of adverse drug reactions (ADRs),	7 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Coefficient of Variation (DF) of Pharmacokinetic Parameter	This outcome assesses the variability in pharmacokinetic parameters such as Cmax and AUCτ to understand inter- and intra-subject variability.	4 weeks
Apparent Clearance (CL/F)	This outcome evaluates the rate of drug clearance from the plasma after oral administration of FHND1002.	4 weeks
Apparent Volume of Distribution (Vz/F)	This outcome assesses the apparent volume of distribution of FHND1002 following oral administration, providing an estimate of drug distribution in the body.	4 weeks

Collaborators and Investigators

• Sponsor: Jiangsu Chia Tai Fenghai Pharmaceutical Co., Ltd.
• Investigators: Principal Investigator: Ting Wang, LanZhou University

Publications and helpful links

General Publications

• Yu CH, Davidson S, Harapas CR, Hilton JB, Mlodzianoski MJ, Laohamonthonkul P, Louis C, Low RRJ, Moecking J, De Nardo D, Balka KR, Calleja DJ, Moghaddas F, Ni E, McLean CA, Samson AL, Tyebji S, Tonkin CJ, Bye CR, Turner BJ, Pepin G, Gantier MP, Rogers KL, McArthur K, Crouch PJ, Masters SL. TDP-43 Triggers Mitochondrial DNA Release via mPTP to Activate cGAS/STING in ALS. Cell. 2020 Oct 29;183(3):636-649.e18. doi: 10.1016/j.cell.2020.09.020. Epub 2020 Oct 7.
• Watanabe H, Atsuta N, Hirakawa A, Nakamura R, Nakatochi M, Ishigaki S, Iida A, Ikegawa S, Kubo M, Yokoi D, Watanabe H, Ito M, Katsuno M, Izumi Y, Morita M, Kanai K, Taniguchi A, Aiba I, Abe K, Mizoguchi K, Oda M, Kano O, Okamoto K, Kuwabara S, Hasegawa K, Imai T, Kawata A, Aoki M, Tsuji S, Nakashima K, Kaji R, Sobue G. A rapid functional decline type of amyotrophic lateral sclerosis is linked to low expression of TTN. J Neurol Neurosurg Psychiatry. 2016 Aug;87(8):851-8. doi: 10.1136/jnnp-2015-311541. Epub 2016 Jan 8.
• Xu L, Liu T, Liu L, Yao X, Chen L, Fan D, Zhan S, Wang S. Global variation in prevalence and incidence of amyotrophic lateral sclerosis: a systematic review and meta-analysis. J Neurol. 2020 Apr;267(4):944-953. doi: 10.1007/s00415-019-09652-y. Epub 2019 Dec 3.
• Zhang J, Northoff G. Author Correction: Beyond noise to function: reframing the global brain activity and its dynamic topography. Commun Biol. 2022 Dec 21;5(1):1397. doi: 10.1038/s42003-022-04379-5. No abstract available.
• Baughn MW, Melamed Z, Lopez-Erauskin J, Beccari MS, Ling K, Zuberi A, Presa M, Gonzalo-Gil E, Maimon R, Vazquez-Sanchez S, Chaturvedi S, Bravo-Hernandez M, Taupin V, Moore S, Artates JW, Acks E, Ndayambaje IS, Agra de Almeida Quadros AR, Jafar-Nejad P, Rigo F, Bennett CF, Lutz C, Lagier-Tourenne C, Cleveland DW. Mechanism of STMN2 cryptic splice-polyadenylation and its correction for TDP-43 proteinopathies. Science. 2023 Mar 17;379(6637):1140-1149. doi: 10.1126/science.abq5622. Epub 2023 Mar 16.
• Fang MY, Markmiller S, Vu AQ, Javaherian A, Dowdle WE, Jolivet P, Bushway PJ, Castello NA, Baral A, Chan MY, Linsley JW, Linsley D, Mercola M, Finkbeiner S, Lecuyer E, Lewcock JW, Yeo GW. Small-Molecule Modulation of TDP-43 Recruitment to Stress Granules Prevents Persistent TDP-43 Accumulation in ALS/FTD. Neuron. 2019 Sep 4;103(5):802-819.e11. doi: 10.1016/j.neuron.2019.05.048. Epub 2019 Jul 1.
• Piol D, Robberechts T, Da Cruz S. Lost in local translation: TDP-43 and FUS in axonal/neuromuscular junction maintenance and dysregulation in amyotrophic lateral sclerosis. Neuron. 2023 May 3;111(9):1355-1380. doi: 10.1016/j.neuron.2023.02.028. Epub 2023 Mar 23.
• Mead RJ, Shan N, Reiser HJ, Marshall F, Shaw PJ. Amyotrophic lateral sclerosis: a neurodegenerative disorder poised for successful therapeutic translation. Nat Rev Drug Discov. 2023 Mar;22(3):185-212. doi: 10.1038/s41573-022-00612-2. Epub 2022 Dec 21.
• Sheridan C. Unprecedented blood biomarker enables ALS drug approval. Nat Biotechnol. 2023 Jul;41(7):886-888. doi: 10.1038/s41587-023-01862-0. No abstract available.
• Mullard A. ALS antisense drug falters in phase III. Nat Rev Drug Discov. 2021 Dec;20(12):883-885. doi: 10.1038/d41573-021-00181-w. No abstract available.
• Todd TW, Petrucelli L. Modelling amyotrophic lateral sclerosis in rodents. Nat Rev Neurosci. 2022 Apr;23(4):231-251. doi: 10.1038/s41583-022-00564-x. Epub 2022 Mar 8.

Study record dates

Study Major Dates

• Study Start (Actual): July 5, 2024
• Primary Completion (Estimated): March 3, 2025
• Study Completion (Estimated): June 5, 2025

Study Registration Dates

• First Submitted: January 14, 2025
• First Submitted That Met QC Criteria: January 14, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 14, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: FHND1002; Amyotrophic Lateral Sclerosis(ALS)
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Pathologic Processes; Neuromuscular Diseases; Metabolic Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Sclerosis; Motor Neuron Disease; Amyotrophic Lateral Sclerosis
• Other Study ID Numbers: FHND1002-I-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Due to privacy and confidentiality concerns, individual participant data (IPD) will not be shared. The data contains sensitive health information that is protected by regulations, and sharing it may compromise participant confidentiality.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No