Clinical trial NCT06685809: A Phase 1 Study of FZ008-145 in Healthy Subjects.
Official title: A Phase 1, Randomized, Double-Blind, Single Ascending Dose Study to Assess the Safety, Tolerability and Pharmacokinetics of FZ008-145 Solution in Healthy Subjects (Part A); A Randomized, Double-Blind, Single Ascending Dose Study to Assess the Safety, Tolerability and Pharmacokinetics of FZ008-145 Tablet in Healthy Subjects (Part B); A Randomized, Open-label, 2-period, 2-treatment (2×2) Crossover Study to Assess the Food Effect on Bioavailability of FZ008-145 Tablet in Healthy Subjects (Part C)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Guangzhou Fermion Technology Co., LTD
Sponsor class: INDUSTRY
First posted: 2024-11-13
Enrollment: 84
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: The study will be conducted in 3 parts: Part A (single ascending dose \[SAD\] in solution formulation), Part B (SAD in tablet formulation), and Part C (food effect \[FE\]).

Detailed description: * Part A is a randomized, double-blind, placebo-controlled, SAD study to assess safety, tolerability, and pharmacokinetics (PK) of FZ008-145 solution in healthy subjects. Up to 40 subjects will be enrolled in 5 cohorts.
* Part B is a randomized, double-blind, placebo-controlled, SAD study to assess safety, tolerability, and PK of FZ008-145 tablet in healthy subjects. Up to 24 subjects will be enrolled in 3 cohorts.
* Part C is a randomized, open-label, 2-period, 2-treatment (2×2) crossover study to assess the effect of food on bioavailability of FZ008-145 tablet in healthy subjects. A total of 20 healthy subjects will be allocated to 2 cohorts

Eligibility criteria: Inclusion Criteria:

1. Able and willing to provide written informed consent after the nature of the study has been explained and prior to the commencement of any study procedures.
2. Male or female aged 18 to 65 years (inclusive).
3. Subject has body mass index of 18 to 32 kg/m2 with a minimum body weight of 50 kg for males, and 45 kg for females (inclusive).
4. Subject is generally healthy, in the opinion of the Investigator, based on assessment of medical history, physical examination, vital signs, electrocardiogram (ECG), and other relevant tests conducted at Screening and Day -1 at the discretion of the Investigator or designee. Tests could be repeated once if they are outside the relevant clinical reference range.
5. Subject has clinical laboratory values (based on hematology, coagulation, biochemistry, and urinalysis parameters) within normal range, as specified by the testing laboratory, at Screening and Day -1, unless deemed not clinically significant by the Investigator or delegate. Tests could be repeated once if they are outside the relevant clinical reference range.
6. Females must not be pregnant or lactating, and must use acceptable, highly effective double contraception from Screening until 90 days after study completion, including the Follow-up period. Women of childbearing potential (WOCBP) must have a negative pregnancy test at Screening and Day -1 and be willing to have additional pregnancy tests as required throughout the study. Women not of childbearing potential must be postmenopausal for ≥ 12 months (postmenopausal status is to be confirmed through testing of follicle stimulating hormone (FSH) levels ≥ 40 IU/L at Screening for amenorrhoeic female subjects). Females must not donate eggs from the first dose of IP until at least 90 days after the last dose of IP. Males must be surgically sterile (\> 90 days since vasectomy with no viable sperm), or if engaged in sexual relations with a WOCBP, either his partner must be surgically sterile (e.g., tubal occlusion, hysterectomy, bilateral salpingectomy, bilateral oophorectomy), or an acceptable, highly effective contraceptive method must be used from Screening until study completion, including the Follow-up period, and 90 days. Males with same-sex partners (abstinence from penile-vaginal intercourse) or are abstinent from heterosexual intercourse are not required to use contraception. Males must not donate sperm from the first dose of IP until at least 90 days after the last dose of IP.

8.Willing and able to comply with all study-related procedures and assessments, including confinement and attending necessary visits to the CRU.

Exclusion Criteria:

1. Has special dietary requirements that are not conducive to consuming a high-fat breakfast diet (For Part C only).
2. Has history of febrile illness or evidence of active infection within 14 days prior to the first dose of IP.
3. Substance abuse-related disorder or a history of drug, and/or substance abuse deemed significant by the Investigator. Positive drug screen at Screening and Day -1. The test could be repeated once at the discretion of Investigator/designee.
4. Has consumed more than 14 units of alcohol per week in the 3 months prior to signing the ICF (1 unit = 360 mL of beer with an alcohol content of 5%, or 45 mL of spirits with an alcohol content of 40%, or 150 mL of wine with an alcohol content of 12%), or has a positive alcohol breath test (breath alcohol concentration \> 0.0 mg/100 mL) at Screening and Day -1, or unable to abstain from alcohol during the trial period. The test could be repeated once at the discretion of the Investigator/designee.
5. History of alcohol allergy.
6. Has excessively used nicotine products (average daily smoking of more than 5 cigarettes) within the 3 months prior to Screening or refuse to abstain from smoking during the trial or has a positive nicotine/cotinine test at Day -1.
7. Participated in any other investigational trials or has been exposed to other investigational drugs within 28 days or 5 half-lives of the previously administered investigational drug (date derived from last study procedure \[blood collection or dosing\] of previous trial), whichever is longer, prior to admission to the CRU.
8. Positive test for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody and human immunodeficiency virus (HIV) antibody at Screening.
9. Donation of blood or significant blood loss ≥ 400 mL in 1 month prior to the first IP administration, has received a blood transfusion or used blood products within 1 month prior to first dosing, or plan to donate blood during this trial or within 1 month after the last IP administration.
10. Plasma donation within 14 days prior to the first administration of IP.
11. Has used any medication within 14 days prior to the first IP administration that the Investigator considers may affect the PK evaluation of the study drug (including prescription drugs, over-the-counter drugs, herbal medicines, functional vitamins, dietary supplements, etc.).
12. History of previous QTc prolongation, or clinically significant abnormal ECG finding at Screening:

    1. Heart rate 45 to 100 beats per minute.
    2. PR 120 to 220 msec.
    3. QRS \< 120 msec.
    4. QTcF ≥ 450 msec for males or QTcF ≥ 470 msec for females (confirmed by repeated examinations).
    5. Long QT syndrome.
    6. Use of concomitant medications that are known to prolong QT/QTc.
    7. Abnormal ECG findings as judged by the Investigator.
13. Has liver disease or clinically significant liver impairment at Screening (e.g., aspartate aminotransferase \[AST\], alanine aminotransferase \[ALT\], or total bilirubin \> 1.5 times the upper limit of normal \[ULN\]).
14. Has had major surgery within 6 months prior to the Screening, or plan to have any surgeries during their participation in trial.
15. Has any disease or condition that may interfere with the absorption/distribution/metabolism/excretion of the study drug, in the opinion of the Investigator (e.g., dysphagia, gastrointestinal diseases, cholecystectomy).
16. Presence of diseases such as migraine, cardiovascular, liver, endocrine, gastrointestinal, metabolic, neurological, pulmonary, endocrine, psychiatric, or oncological history, or any other evidence deemed to be clinically significant by the Investigator and that may pose a risk to the safety of the subject or interfere with the conduct, progress, or completion of the study.
17. Previous or suspected history of hypersensitivity or allergic reactions to the active ingredients of the study drug or other drugs and food.
18. Consumption of foods or juices containing cranberries or pineapples, Seville oranges, grapefruit, pomegranate or caffeine (xanthine-containing products) for 48 hours before the start of dosing until after collection of the final PK, unless deemed acceptable by the Investigator.
19. Subjects with other factors deemed ineligible to participate in the trial by the Investigator.

Primary outcomes:
measure: To assess the safety of FZ008-145 solution by number of adverse events (AEs) and treatment-emergent adverse events (TEAEs)
timeFrame: up to 14 days post first dose administration
measure: To assess the safety of FZ008-145 tablet by number of adverse events (AEs) and treatment-emergent adverse events (TEAEs)
timeFrame: up to 14 days post first dose administration
measure: Number of participants with changes in laboratory parameters determined as adverse events following oral dose of FZ008-145 solution and FZ008-145 tablet
timeFrame: up to 14 days post first dose administration
measure: To assess effect of high-fat meal on pharmacokinetics (PK) of FZ008-145 tablet -Cmax (maximum plasma concentration)
timeFrame: Up to 5 days post first dose administration
measure: To assess effect of high-fat meal on pharmacokinetics (PK) of FZ008-145 tablet -AUC0-last (Area under curve from 0 to last)
timeFrame: Up to 5 days post first dose administration
measure: To assess effect of high-fat meal on pharmacokinetics (PK) of FZ008-145 tablet -AUC0-inf (Area under curve from 0 to infinity)
timeFrame: Up to 5 days post first dose administration
Secondary outcomes:
measure: To evaluate the pharmacokinetics (PK) of FZ008-145 solution and FZ008-145 tablet
timeFrame: Up to 5 days post first dose administration
measure: To evaluate the pharmacokinetics (PK) of FZ008-145 solution and FZ008-145 tablet
timeFrame: Up to 5 days post first dose administration
measure: To evaluate the pharmacokinetics (PK) of FZ008-145 solution and FZ008-145 tablet
timeFrame: Up to 5 days post first dose administration
measure: To evaluate the pharmacokinetics (PK) of FZ008-145 solution and FZ008-145 tablet
timeFrame: Up to 5 days post first dose administration
measure: To evaluate the pharmacokinetics (PK) of FZ008-145 solution and FZ008-145 tablet
timeFrame: Up to 5 days post first dose administration
measure: To evaluate the pharmacokinetics (PK) of FZ008-145 solution and FZ008-145 tablet
timeFrame: Up to 5 days post first dose administration
measure: To evaluate the pharmacokinetics (PK) of FZ008-145 solution and FZ008-145 tablet
timeFrame: Up to 5 days post first dose administration
measure: To evaluate the pharmacokinetics (PK) of FZ008-145 solution and FZ008-145 tablet
timeFrame: Up to 4 days post first dose administration
measure: To evaluate the pharmacokinetics (PK) of FZ008-145 solution and FZ008-145 tablet
timeFrame: Up to 4 days post first dose administration
measure: To evaluate the pharmacokinetics (PK) of FZ008-145 solution and FZ008-145 tablet
timeFrame: Up to 4 days post first dose administration
measure: To assess the safety of FZ008-145 tablet by number of adverse events (AEs) and treatment-emergent adverse events (TEAEs) in Part C
timeFrame: up to 14 days post first dose administration
Other outcomes:
Locations:
city: Adelaide
country: Australia
facility: CMAX Clinical Research Pty
state: South Australia
Study officials:
affiliation: Guangzhou Fermion Technology Co., LTD
name: Shiqun Zhang
role: STUDY_DIRECTOR
References: