An Open-Label PET/CT Imaging Study to Evaluate Brain Serotonin Transporter (SERT) Occupancy Following Single-Dose Administration of LG-0317 Tablets in Healthy Participants

Обзор

The purpose of the study is to evaluate brain serotonin transporter (SERT) receptor occupancy (RO) following single oral doses of LG-0317 tablets in healthy male participants; and to explore the pharmacokinetic/pharmacodynamic (PK/PD) relationship between LG-0317 plasma concentrations and SERT occupancy..

Подробное описание

This is a single-center, open-label, adaptive-design, exploratory Phase I PET/CT imaging study involving single-dose administration in healthy male participants. The study aims to evaluate brain serotonin transporter (SERT) occupancy following administration of LG-0317 using positron emission tomography (PET) and to investigate the pharmacokinetic/pharmacodynamic (PK/PD) relationship between plasma concentrations of LG-0317 and receptor occupancy.

The study employs a parallel-group, adaptive design without blinding, randomization, or placebo control. A total of 12 participants are anticipated to be enrolled and allocated into three dose cohorts.

Вмешательства

• Препарат Cohort 1: LG-0317 20 mg
  Subjects will receive single dose of LG-0317 tablets.
• Препарат Cohort 1: LG-0317 40 mg
  Subjects will receive single dose of LG-0317 tablets.
• Препарат Cohort 1: LG-0317 80 mg
  Subjects will receive single dose of LG-0317 tablets.

Первичные конечные точки

• Receptor Occupancy: SERT occupancy in brain ROIs post single-dose of LG-0317 as measured by PET/CT. [Срок оценки: Day 1]

Вторичные конечные точки (6)

• Pharmacokinetics: maximum plasma concentration (Cmax) [Срок оценки: Day 3]
• Pharmacokinetics: time to reach Cmax(Tmax) [Срок оценки: Day 3]
• Pharmacokinetics: area under the plasma concentration-time curve from time zero to the last quantifiable concentration (AUC0-t) [Срок оценки: Day 3]
• Number of participants experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) [Срок оценки: Day 10]
• Number of participants with clinically significant laboratory assessment abnormalities [Срок оценки: Day 10]
• Number of participants with clinically significant Vital sign abnormalities [Срок оценки: Day 10]

Критерии участия

Критерии включения

Healthy male subjects age 18 to 45 years of age included.

• Participant must weigh at least 50 kg to participate in the study, and must have a body mass index (BMI) within the range of 19-28 kg/m2 inclusive.
• The participant has normal results or abnormalities without clinical significance as judged by the investigator for vital signs, physical examination, laboratory tests (complete blood count, blood biochemistry, coagulation function, urinalysis), 12-lead electrocardiogram (ECG.
• Fully understand the trial content, procedures, and possible adverse reactions; voluntarily participate and sign the informed consent form (ICF).
• Able to communicate well with the study personnel, and understand and comply with the relevant requirements of the trial.

Критерии исключения

• 1\) Allergic constitution, history of allergic diseases, or known allergy to the investigational product, its excipients, or related products.

2\) History of current or prior neurological disorders, including but not limited to: history of head trauma or concussion; history of stroke or known cerebrovascular diseases (e.g., intracranial aneurysm, arteriovenous malformation); or other known structural abnormalities of the brain.

3\) History of serious unstable diseases or related medical history affecting the hepatic, renal, gastrointestinal, endocrine, cardiovascular (including known aneurysmal vascular lesions), metabolic, hematological, respiratory, or autoimmune systems.

4\) History of psychiatric disorders, substance abuse, or drug dependence. 5) Presence of epileptiform abnormalities (EAs) on screening electroencephalogram (EEG). (Screening EEG will include hyperventilation and intermittent photic stimulation as activation procedures.) 6) Personal history of epilepsy or family history of epilepsy in first-degree relatives (i.e., parents, siblings, or children).

7\) Suicidal risk as assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS); specifically, if the participant answers "yes" to Question 4 or 5 of the Suicidal Ideation section of the C-SSRS during screening and the most recent intent or plan occurred within the past 6 months; or answers "yes" to any question in the Suicidal Behavior section occurring within the past 2 years; or deemed at suicidal risk based on the investigator's clinical judgment.

8\) Any relevant history of illness, surgery, or trauma within 3 months prior to the first dose that could affect safety or pharmacokinetics, or planned surgery during the study period.

9\) Inability to swallow tablets. 10) Difficult venous access, intolerance to venipuncture/indwelling catheters, or history of vasovagal syncope (fainting) related to needles/blood (needle-phobia or hemophobia).

11\) Excessive consumption (>8 cups/day; 1 cup = 250 mL) of tea, coffee, or caffeinated beverages within 3 months prior to screening; or consumption of chocolate, caffeine-containing products, alcohol, grapefruit/grapefruit juice, or xanthine-rich foods/beverages within 48 hours prior to the first dose.

12\) Alcohol consumption exceeding 21 standard units per week within 3 months prior to screening (1 standard unit contains 14 g of alcohol, e.g., 360 mL beer, 45 mL liquor at 40% alcohol, or 150 mL wine); or positive result on breath alcohol testing.

13\) Smoking history ≥5 cigarettes per day within 3 months prior to screening. 14) Use of any prescription drugs, over-the-counter medications, herbal remedies, or dietary supplements within 14 days prior to the first dose.

15\) Participation in another clinical trial involving investigational product within 3 months prior to the first dose.

16\) Blood donation or significant blood loss (>400 mL), or receipt of blood transfusion within 3 months prior to the first dose.

17\) Participation in a clinical study involving radiation exposure within the past 12 months, or receipt of significant diagnostic/therapeutic radiation exposure for medical reasons within the past 12 months, leading to an estimated cumulative annual radiation dose exceeding safety limits (e.g., ≥10 mSv) based on ICRP recommendations.

18\) Any contraindication to PET/CT or MRI scanning, including but not limited to: presence of implanted metallic objects (e.g., cardiac pacemaker, metal prosthesis, implanted neurostimulator); claustrophobia; or body habitus/weight unsuitable for the PET/CT or MRI scanner bore. Note: Contraindications identified during any prior MRI scan or the baseline MRI conducted prior to the screening PET/CT scan also apply.

19\) Positive results for hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV-Ab), human immunodeficiency virus antibody (HIV-Ab), or Treponema pallidum antibody (syphilis).

20\) Use of illicit drugs within 3 months prior to screening or positive urine drug screen (including morphine, methamphetamine, methadone, phencyclidine \[PCP\], tetrahydrocannabinol carboxylic acid \[THC-COOH\], amphetamine, cocaine, barbiturates, benzodiazepines, ketamine, tricyclic antidepressants).

21\) Plan to conceive, donate sperm, or unwillingness to use effective contraception during the study and for 3 months after the last dose.

22\) Known photosensitive disorder or history of abnormal sensitivity to sunlight.

23\) Affiliation with the study site staff, employment by the sponsor, or being an immediate family member of such personnel.

24\) Any other condition that, in the investigator's opinion, makes the participant unsuitable for inclusion in the study.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT07708428 · LG-0317-RO-01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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