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
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
A single dose of 37.5mg BSY001 for injection.
A single dose of 75 mg BSY001 for injection.
A single dose of 150 mg BSY001 for injection.
Shulan (Hangzhou) Hospital
Hangzhou, China
RECRUITINGSafety and Tolerability Parameters (SAD) - TEAE
Number and percentage of TEAE
Time frame: 10 days
Safety and Tolerability (SAD) - Lab tests
Lab tests (complete blood count, serum biochemistry, and coagulation parameters) at baseline compared to Lab tests 4 days and 10 days post dose.
Time frame: Day 4 and day 10 post dose
Safety and Tolerability (SAD) - Physical Examination
Physical Examination at Baseline Compared to Physical Examination 4,10 Days Post Dose
Time frame: Day 4 and Day 10
Safety and Tolerability Parameters (SAD) - Vital Signs
Vital signs at baseline compared to Vital signs (temperature, blood pressure, pulse, breath) day 1 pre dose, day 1, 2, 3, 4, and 10 post dose
Time frame: Day 1 pre dose; Day 1, 2, 3, 4, and 10 post dose
Safety and Tolerability (SAD) - Electrocardiogram
Electrocardiogram at Baseline Compared to Electrocardiogram day 1 pre dose, 1, 4, 10 Days Post Dose
Time frame: Day 1 pre dose, Day 1, 4, 10 post dose
Pharmacokinetics (MAD) - Cmax
Maximum observed plasma drug concentration.
Time frame: 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
Steady-state peak plasma concentration
Time frame: 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.
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QUADRUPLE
Enrollment
76
A single dose of 200 mg BSY001 for injection.
A single dose of 300 mg BSY001 for injection.
A single dose for injection.
Administer 200 mg of BSY001 every 12 hours for 14 consecutive days.
Administer placebo every 12 hours for 14 consecutive days.
Pharmacokinetics (MAD) - Cmin,ss
Steady-state trough plasma concentration
Time frame: 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
Steady-state trough concentration
Time frame: 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
Time to peak concentration
Time frame: 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,ss
Steady-state time to peak concentration
Time frame: 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) - AUC0-t
Area under the plasma concentration-time curve from time 0 to the last measurable concentration
Time frame: 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) - AUC0-∞
Area under the plasma concentration-time curve from time 0 extrapolated to infinity
Time frame: 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) - AUC0-12h, AUC0-24h
Area under the plasma concentration-time curve from 0 to 12 hours and 0 to 24 hours
Time frame: 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) - t½,z
Terminal elimination half-life
Time frame: 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) - λz
Terminal elimination rate constant
Time frame: 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) - CLz
Clearance
Time frame: 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) - Vz
Apparent volume of distribution
Time frame: 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) - RCmax
Accumulation ratio based on Cmax
Time frame: 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) - RAUC
Accumulation ratio based on AUC
Time frame: 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 (SAD) - Cmax
Maximum observed plasma drug concentration 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.
Time frame: 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
Time to reach Cmax 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.
Time frame: 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
Area under the plasma concentration vs. time curve (AUC) from time 0 to the last quantifiable measurement. Samples were collected 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.
Time frame: 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-∞
AUC from time 0 extrapolated to infinity
Time frame: 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
Area under the plasma concentration vs. time curve (AUC) from time 0 to the 12-hour time-point
Time frame: 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
Area under the plasma concentration vs. time curve (AUC) from time 0 to the 24-hour time-point
Time frame: 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
Terminal elimination half-life
Time frame: 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
Terminal elimination rate constant
Time frame: 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
Apparent total body clearance
Time frame: 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
Apparent volume of distribution
Time frame: 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
Number and percentage of TEAE
Time frame: 20 days
Safety (MAD) - Lab tests
Lab tests (complete blood count, serum biochemistry, and coagulation parameters) at baseline compared to Lab tests at day 2\~6, day 7 and day 14, day 20.
Time frame: day 2~6, day 7 and day 14, day 20.
Safety (MAD) - Physical Examination
Physical Examination at Baseline Compared to Physical Examination at day 20
Time frame: Day 20
Safety (MAD) - Electrocardiogram
Electrocardiogram at Baseline Compared to Electrocardiogram 1 day pre dose, day 1, 2\~6, 7, 14, 20.
Time frame: 1 day pre dose, day 1, 2~6, 7, 14, 20.
Safety (MAD) - Vital Signs
Vital signs at baseline compared to Vital signs (temperature, blood pressure, pulse, breath) day 1 pre dose, day 1, 2\~6, 7,8\~13, 14, and 20
Time frame: day 1 pre dose, day 1, 2~6, 7,8~13, 14, and 20