Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of BSY001 After Single/Multiple Doses.

Официальное название

A Two-Phase, Randomized, Double-Blind, Placebo-Controlled Phase I Clinical Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of BSY001 for Injection Following Single or Multiple Doses in Healthy Subjects.

Обзор

A Two-Phase, Randomized, Double-Blind, Placebo-Controlled Phase I Clinical Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of BSY001 for Injection Following Single or Multiple Doses in Healthy Subjects

Подробное описание

This study is divided into two parts: a single-dose study (BSY001-A) and a multiple-dose study (BSY001-B). Subjects for BSY001-B will be enrolled only after all subjects participating in BSY001-A have completed the pharmacokinetic (PK) tests and safety follow-ups for all dose groups, and the corresponding PK parameters and preliminary safety results have been obtained.

BSY001-A: A single ascending dose study conducted in healthy subjects. The trial includes five dose groups: 37.5, 75, 150, 200, and 300 mg, starting from the low-dose group. A total of 46 subjects are planned for enrollment. For the 37.5 mg and 75 mg dose groups, 8 subjects will be enrolled in each group, with 6 receiving BSY001 for injection and 2 receiving placebo. For the 150 mg, 200 mg, and 300 mg dose groups, 10 subjects will be enrolled in each group, including 8 receiving BSY001 for injection and 2 receiving placebo. All subjects will receive a single administration of either BSY001 for injection or placebo. PK blood samples will be collected both prior to and after the initiation of dosing. Subjects who complete PK blood sampling and safety follow-ups may be discontinued from the study. Tolerability assessment will be performed on Day 4 for each dose group, and dosing of the next dose group may commence only after the Safety Monitoring Committee (SMC) confirms safety and tolerability.

BSY001-B: A randomized, double-blind, multiple-dose pharmacokinetic study conducted in healthy subjects. A total of 30 eligible subjects will be enrolled after screening, including 24 in the treatment group and 6 in the placebo group. Subjects will receive 200 mg of BSY001 for injection or placebo, administered once every 12 hours ± 10 minutes for 14 consecutive days. During hospitalization, subjects will be under centralized management by the study center, with blood sample collection and safety assessments performed as scheduled.

Вмешательства

• Препарат BSY001 for Injection (37.5mg)
  A single dose of 37.5mg BSY001 for injection.
• Препарат BSY001 for Injection (75 mg)
  A single dose of 75 mg BSY001 for injection.
• Препарат BSY001 for Injection (150 mg)
  A single dose of 150 mg BSY001 for injection.
• Препарат BSY001 for Injection (200 mg)
  A single dose of 200 mg BSY001 for injection.
• Препарат BSY001 for Injection (300 mg)
  A single dose of 300 mg BSY001 for injection.
• Препарат placebo-SAD
  A single dose for injection.
• Препарат BSY001 for Injection
  Administer 200 mg of BSY001 every 12 hours for 14 consecutive days.
• Препарат placebo-MAD
  Administer placebo every 12 hours for 14 consecutive days.

Первичные конечные точки

• Safety and Tolerability Parameters (SAD) - TEAE [Срок оценки: 10 days]
• Safety and Tolerability (SAD) - Lab tests [Срок оценки: Day 4 and day 10 post dose]
• Safety and Tolerability (SAD) - Physical Examination [Срок оценки: Day 4 and Day 10]
• Safety and Tolerability Parameters (SAD) - Vital Signs [Срок оценки: Day 1 pre dose; Day 1, 2, 3, 4, and 10 post dose]
• Safety and Tolerability (SAD) - Electrocardiogram [Срок оценки: Day 1 pre dose, Day 1, 4, 10 post dose]
• Pharmacokinetics (MAD) - Cmax [Срок оценки: Day 1/14 (1st/2nd dose): Within 30 min pre-dose; 0.5, 1, 2, 4, 6 ,6.5, 8, 9, 10, 12 hours post-dose. Day 4, 6, 12, 13: Within 30 min before daily first dose. 24, 48, 72, 96, 120, 144 hours after the first dose on Day 14.]
• Pharmacokinetics (MAD) - Cmax,ss [Срок оценки: Day 1/14 (1st/2nd dose): Within 30 min pre-dose; 0.5, 1, 2, 4, 6 ,6.5, 8, 9, 10, 12 hours post-dose. Day 4, 6, 12, 13: Within 30 min before daily first dose. 24, 48, 72, 96, 120, 144 hours after the first dose on Day 14.]
• Pharmacokinetics (MAD) - Cmin,ss [Срок оценки: Day 1/14 (1st/2nd dose): Within 30 min pre-dose; 0.5, 1, 2, 4, 6 ,6.5, 8, 9, 10, 12 hours post-dose. Day 4, 6, 12, 13: Within 30 min before daily first dose. 24, 48, 72, 96, 120, 144 hours after the first dose on Day 14.]
• Pharmacokinetics (MAD) - Ctrough,ss [Срок оценки: Day 1/14 (1st/2nd dose): Within 30 min pre-dose; 0.5, 1, 2, 4, 6 ,6.5, 8, 9, 10, 12 hours post-dose. Day 4, 6, 12, 13: Within 30 min before daily first dose. 24, 48, 72, 96, 120, 144 hours after the first dose on Day 14.]
• Pharmacokinetics (MAD) - Tmax [Срок оценки: Day 1/14 (1st/2nd dose): Within 30 min pre-dose; 0.5, 1, 2, 4, 6 ,6.5, 8, 9, 10, 12 hours post-dose. Day 4, 6, 12, 13: Within 30 min before daily first dose. 24, 48, 72, 96, 120, 144 hours after the first dose on Day 14.]

Вторичные конечные точки (12)

• Pharmacokinetics (SAD) - Cmax [Срок оценки: Before administration (within 0.5 hours); and at 0.5, 1, 2, 4, 6 (immediately post-dosing), 6.5, 8, 9, 10, 12, 16, 24, 48, and 72 hours after administration.]
• Pharmacokinetics (SAD) - Tmax [Срок оценки: Before administration (within 0.5 hours); and at 0.5, 1, 2, 4, 6 (immediately post-dosing), 6.5, 8, 9, 10, 12, 16, 24, 48, and 72 hours after administration.]
• Pharmacokinetics (SAD) - AUC0-t [Срок оценки: Before administration (within 0.5 hours); and at 0.5, 1, 2, 4, 6 (immediately post-dosing), 6.5, 8, 9, 10, 12, 16, 24, 48, and 72 hours after administration.]
• Pharmacokinetics (SAD) - AUC0-∞ [Срок оценки: Before administration (within 0.5 hours); and at 0.5, 1, 2, 4, 6 (immediately post-dosing), 6.5, 8, 9, 10, 12, 16, 24, 48, and 72 hours after administration.]
• Pharmacokinetics - AUC0-12h [Срок оценки: Before administration (within 0.5 hours); and at 0.5, 1, 2, 4, 6 (immediately post-dosing), 6.5, 8, 9, 10, 12, 16, 24, 48, and 72 hours after administration.]
• Pharmacokinetics (SAD) - AUC0-24h [Срок оценки: Before administration (within 0.5 hours); and at 0.5, 1, 2, 4, 6 (immediately post-dosing), 6.5, 8, 9, 10, 12, 16, 24, 48, and 72 hours after administration.]
• Pharmacokinetics (SAD) - t1/2 z [Срок оценки: Before administration (within 0.5 hours); and at 0.5, 1, 2, 4, 6 (immediately post-dosing), 6.5, 8, 9, 10, 12, 16, 24, 48, and 72 hours after administration.]
• Pharmacokinetics (SAD) - λz [Срок оценки: Before administration (within 0.5 hours); and at 0.5, 1, 2, 4, 6 (immediately post-dosing), 6.5, 8, 9, 10, 12, 16, 24, 48, and 72 hours after administration.]
• Pharmacokinetics (SAD) - CLz [Срок оценки: Before administration (within 0.5 hours); and at 0.5, 1, 2, 4, 6 (immediately post-dosing), 6.5, 8, 9, 10, 12, 16, 24, 48, and 72 hours after administration.]
• Pharmacokinetics (SAD) - Vz [Срок оценки: Before administration (within 0.5 hours); and at 0.5, 1, 2, 4, 6 (immediately post-dosing), 6.5, 8, 9, 10, 12, 16, 24, 48, and 72 hours after administration.]
• Safety (MAD) - TEAE [Срок оценки: 20 days]
• Safety (MAD) - Lab tests [Срок оценки: day 2~6, day 7 and day 14, day 20.]

Критерии участия

Критерии включения

• Subjects voluntarily participate in the study, sign the informed consent form, and agree to comply with all study requirements;
• Aged ≥ 18 years and ≤ 50 years (based on the date of signing the informed consent form), including both males and females;
• Body Mass Index (BMI) between 19.0 and 30.0 kg/m² (19.0 and 30.0 kg/m² inclusive); for female subjects, body weight between 45.0 and 120.0 kg (45.0 kg inclusive and 120.0 kg exclusive); for male subjects, body weight between 50.0 and 120.0 kg (50.0 kg inclusive and 120.0 kg exclusive);
• Subjects (including their partners) voluntarily adopt effective contraceptive measures from 1 month before screening to 6 months after the last administration of the study drug, and have no plans for childbearing, sperm donation, or egg donation within the next 6 months.

Критерии исключения

• Subjects with a known allergy to Tecovirimat drugs, any excipient ingredients in this product, or subjects with an allergic diathesis (allergic to ≥ 2 types of substances);
• Subjects with clinically significant abnormal electrocardiogram (ECG) findings or QTc prolongation as determined by the investigator (e.g., QTc interval ≥ 450 ms in males and ≥ 470 ms in females, with QTc interval calculated using the Fridericia formula);
• Subjects with a creatinine clearance rate (Cockcroft-Gault formula) < 90 mL/min;
• Subjects with clinically significant abnormalities in physical examination, vital signs, laboratory tests, or other auxiliary examinations as determined by the investigator;
• Subjects with current or past history of the following clinically significant diseases as determined by the investigator, including but not limited to diseases of the cardiovascular system, respiratory system, digestive system, urinary system, endocrine system, immune system, and nervous system (e.g., epilepsy);
• Subjects with a current or history (within the past 3 months) of bacterial, fungal, or mycobacterial infection.;
• Subjects with known clinically significant acute/chronic viral infections;
• Subjects with a history of severe headache or migraine;
• Subjects who have undergone major surgery within 6 months before drug administration, or plan to undergo surgery from the time of signing the informed consent form to 1 month after the end of the trial;
• Subjects who have donated blood or had massive blood loss (> 450 mL) within 3 months before screening;
• Subjects who smoked more than 5 cigarettes per day within 3 months before signing the informed consent form, or cannot refrain from using any tobacco products during the trial;
• Subjects who consumed more than 14 units of alcohol per week within 3 months before signing the informed consent form (1 unit of alcohol ≈ 360 mL of beer, or 45 mL of spirits with 40% alcohol content, or 150 mL of wine), had a positive alcohol breath test (breath alcohol content > 0 mg/100 mL), or cannot abstain from alcohol during the trial;
• Subjects who consumed grapefruit, grapefruit juice, chocolate, strong tea, coffee, or other beverages containing caffeine or alcohol within 72 hours before drug administration, or refuse to stop consuming the aforementioned beverages and foods during the trial;
• Subjects who plan to engage in strenuous exercise during the trial, including contact sports or collision sports;
• Subjects with a positive urine drug screen (for morphine, methamphetamine, ketamine, 3,4-methylenedioxymethamphetamine, or tetrahydrocannabinolic acid), or a history of drug abuse or drug use within 5 years before screening;
• Subjects with a positive result in any of the following tests: hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (IgG), hepatitis C virus core antigen, human immunodeficiency virus (HIV) antibody, or treponema pallidum-specific antibody (TP-Ab);
• Subjects who participated in other drug clinical trials within 3 months before screening (calculated starting from the time of the last drug administration in the previous trial);
• Subjects who took any prescription drugs, over-the-counter drugs, or traditional Chinese herbal medicines within 30 days before screening;
• Subjects with a positive pregnancy test result;
• Subjects who cannot tolerate venipuncture, or have a history of hematophobia (fear of blood) or trypanophobia (fear of needles);
• Subjects who developed an acute illness or required concomitant medication from the screening phase to before the first drug administration;
• Subjects who received a vaccine within 2 weeks before screening, or plan to receive a vaccine during the trial;
• Subjects deemed unsuitable for participation in this trial by the investigator.

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

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Shulan (Hangzhou) Hospital — Ханчжоу

Идентификаторы

NCT: NCT07377175 · BSY001-202401

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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