This is a Phase 1, open-label, dose-escalation, multiple-dose study to investigate pharmacokinetics and safety of JT001 (VV116) in Caucasian healthy subjects.
Subjects will be admitted to the Phase 1 clinical study ward on the day before administration (Day -1, baseline phase), and will be confined until all examinations and assessments are completed on Day 8. Subjects will be followed up on Day 12 (± 1 day); if there are abnormalities, an unscheduled visit may be arranged for subjects at the Investigators discretion. Subjects who withdraw early should be encouraged to complete the early withdrawal visit. At the Screening visit, subjects who are willing to take part in the study will sign informed consent forms (ICFs) and complete the screening examinations. Subjects who meet all of the inclusion criteria and none of the exclusion criteria will be assigned to receive the investigational product (IP) at 1 of the 3 doses according to the dose-escalation scheme, and will be followed up until the 6th day after the last administration. Time of Collection of PK Blood Samples To gather the PK data, PK blood samples will be collected at the following specified times: Day 1: pre-dose (within 1 h before the first administration), and at 10 min, 20 min, 30 min, 45 min, 1 hour, 1.5 hours, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, and 12 hours after the first administration. Day 5: pre-dose (within 0.5 hour before each administration) Day 6: pre-dose (within 0.5 hour before administration), and at 10 min, 20 min, 30 min, 45 min, 1 hour, 1.5 hours, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 24 hours, and 48 hours post-dose. Dose-Escalation Scheme This study consists of 3 dosing group (200, 400, and 600 mg). A dose-escalation design is used, sequentially from the low-dose group to the high-dose group, and each subject will only receive oral administration at one dose level according to the dose-escalation scheme. All subjects will be administered orally twice a day (approximately 12 hours apart) for 6 consecutive days and the last administration will be given in the morning on Day 6. All doses must be taken under fasting conditions.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
JT001 (VV116):200 mg,oral,Twice a day,6 consecutive days and the last administration will be given in the morning on Day 6
JT001 (VV116):400 mg,oral,Twice a day,6 consecutive days and the last administration will be given in the morning on Day 6
JT001 (VV116):600 mg,oral,Twice a day,6 consecutive days and the last administration will be given in the morning on Day 6
To explore the pharmacokinetics of JT001 and its prominent metabolite 116-N1 in Caucasian healthysubjects
Pharmacokinetic (PK) parameters: peak concentration (Cmax) of JT001 (VV116) and its metabolite 116-N1.
Time frame: Day 1,Day 5,Day 6:until 48 hours post-dose.
To explore the pharmacokinetics of JT001 and its prominent metabolite 116-N1 in Caucasian healthysubjects
Pharmacokinetic (PK) parameters : time to peak concentration (Tmax) of JT001 (VV116) and its metabolite 116-N1.
Time frame: Day 1,Day 5,Day 6:until 48 hours post-dose.
To explore the pharmacokinetics of JT001 and its prominent metabolite 116-N1 in Caucasian healthysubjects
Pharmacokinetic (PK) parameters: trough concentration (Ctrough) of JT001 (VV116) and its metabolite 116-N1.
Time frame: Day 1,Day 5,Day 6:until 48 hours post-dose.
To explore the pharmacokinetics of JT001 and its prominent metabolite 116-N1 in Caucasian healthysubjects
Pharmacokinetic (PK) parameters: area under the plasma concentration-time curves (AUC0-t, AUC0-∞, and AUC0-τ) of JT001 (VV116) and its metabolite 116-N1.
Time frame: Day 1,Day 5,Day 6:until 48 hours post-dose.
To explore the pharmacokinetics of JT001 and its prominent metabolite 116-N1 in Caucasian healthysubjects
Pharmacokinetic (PK) parameters: elimination half-life (t1/2) of JT001 (VV116) and its metabolite 116-N1.
Time frame: Day 1,Day 5,Day 6:until 48 hours post-dose.
To explore the pharmacokinetics of JT001 and its prominent metabolite 116-N1 in Caucasian healthysubjects
Pharmacokinetic (PK) parameters: apparent clearance (CL/F) of JT001 (VV116) and its metabolite 116-N1.
Time frame: Day 1,Day 5,Day 6:until 48 hours post-dose.
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To explore the pharmacokinetics of JT001 and its prominent metabolite 116-N1 in Caucasian healthysubjects
Pharmacokinetic (PK) parameters: mean residence time (MRT) of JT001 (VV116) and its metabolite 116-N1.
Time frame: Day 1,Day 5,Day 6:until 48 hours post-dose.
To explore the pharmacokinetics of JT001 and its prominent metabolite 116-N1 in Caucasian healthysubjects
Pharmacokinetic (PK) parameters : apparent volume of distribution (Vz/F) Of JT001 (VV116) and its metabolite 116-N1.
Time frame: Day 1,Day 5,Day 6:until 48 hours post-dose.
To explore the pharmacokinetics of JT001 and its prominent metabolite 116-N1 in Caucasian healthysubjects
Pharmacokinetic (PK) parameters: accumulation ratio (Rac) of JT001 (VV116) and its metabolite 116-N1.
Time frame: Day 1,Day 5,Day 6:until 48 hours post-dose.
To evaluate the safety and tolerability of JT001 tablets in Caucasian healthy subjects after multiple dosesoral administrations.
Safety data: adverse events (AEs). AEs will be coded using the most current version of the MedDRA® Version 25.0 or higher. The numbers of cases and incidences of all TEAEs, drug-related TEAEs, SAEs, and TEAEs leading to withdrawal should be classified and summarised according to the dose group, SOC, and PT. TEAEs will also be summarised by severity and by relationship to study drug.
Time frame: Up to 12 days
To evaluate the safety and tolerability of JT001 tablets in Caucasian healthy subjects after multiple dosesoral administrations.
Safety data: vital signs, Respiration(beats per minute) The number and percentages of subjects with abnormal vital signs (respiration, blood pressure, body temperature, and pulse) will be listed and summarised by treatment and protocol specified collection time point. Observed and change from baseline will be summarised at each protocol specified collection time point by dosing group.
Time frame: Up to 12 days
To evaluate the safety and tolerability of JT001 tablets in Caucasian healthy subjects after multiple dosesoral administrations.
Safety data:vital signs,blood pressure(mm Hg) The number and percentages of subjects with abnormal vital signs (respiration, blood pressure, body temperature, and pulse) will be listed and summarised by treatment and protocol specified collection time point. Observed and change from baseline will be summarised at each protocol specified collection time point by dosing group.
Time frame: Up to 12 days
To evaluate the safety and tolerability of JT001 tablets in Caucasian healthy subjects after multiple dosesoral administrations.
Safety data:vital signs,body temperature(℃) The number and percentages of subjects with abnormal vital signs (respiration, blood pressure, body temperature, and pulse) will be listed and summarised by treatment and protocol specified collection time point. Observed and change from baseline will be summarised at each protocol specified collection time point by dosing group.
Time frame: Up to 12 days
To evaluate the safety and tolerability of JT001 tablets in Caucasian healthy subjects after multiple dosesoral administrations.
Safety data:vital signs,pulse(beats per minute) The number and percentages of subjects with abnormal vital signs (respiration, blood pressure, body temperature, and pulse) will be listed and summarised by treatment and protocol specified collection time point. Observed and change from baseline will be summarised at each protocol specified collection time point by dosing group.
Time frame: Up to 12 days
To evaluate the safety and tolerability of JT001 tablets in Caucasian healthy subjects after multiple dosesoral administrations.
Safety data: laboratory tests,The number and percentages of subjects with abnormal laboratory tests (including haematology, biochemistry, coagulation, and urinalysis) in each dose group will be summarised. All abnormal laboratory test indicators and abnormal clinically significant indicators will be listed.
Time frame: Up to 12 days
To evaluate the safety and tolerability of JT001 tablets in Caucasian healthy subjects after multiple dosesoral administrations.
Safety data: physical examinations, include general appearance, head, ears, eyes, nose, throat, dentition, thyroid, chest (heart, lungs), abdomen, skin, neurological, extremities, back, neck, musculoskeletal, and lymph nodes. The number and percentages of subjects with abnormal physical examination in each dose group will be summarised.
Time frame: Up to 12 days
To evaluate the safety and tolerability of JT001 tablets in Caucasian healthy subjects after multiple dosesoral administrations.
Safety data: 12-lead electrocardiograms (ECGs): heart rate. The number and percentages of subjects with abnormal ECG values will be listed and summarised by treatment by protocol specified collection time point by dosing group.
Time frame: Up to 12 days
To evaluate the safety and tolerability of JT001 tablets in Caucasian healthy subjects after multiple dosesoral administrations.
Safety data: 12-lead electrocardiograms (ECGs): P-R interval. The number and percentages of subjects with abnormal ECG values will be listed and summarised by treatment by protocol specified collection time point by dosing group.
Time frame: Up to 12 days
To evaluate the safety and tolerability of JT001 tablets in Caucasian healthy subjects after multiple dosesoral administrations.
Safety data: 12-lead electrocardiograms (ECGs): QTcF interval. The number and percentages of subjects with abnormal ECG values will be listed and summarised by treatment by protocol specified collection time point by dosing group.
Time frame: Up to 12 days