Phase 1 Single Ascending Doses(SAD): Six cohorts of 53 healthy volunteers (HVs) will receive a single IV bolus injection of study drug or placebo. Phase 1 Multiple Ascending Doses(MAD): Three cohorts of 30 HVs will receive multiple IV bolus injections of study drug or placebo every day. After 7 days of continuous administration, the safety, tolerance and Pharmacokinetic/Pharmacodynamic characteristics of multiple administrations were evaluated.
This study adopts a single-center, randomized, double-blind, placebo-controlled parallel-group, dose-escalation design. This single ascending dose (SAD) study is designed with six dose cohorts: 5 mg, 10 mg, 20 mg, 30 mg, 45 mg, and 60 mg. A total of 53 healthy adult participants are planned to be enrolled. Three participants are planned for the 5 mg cohort, randomized in a 2:1 ratio of investigational product to placebo. Each of the remaining five dose cohorts will enroll 10 participants, randomized in an 8:2 ratio of investigational product to placebo. For the multiple ascending dose (MAD) part, three dose cohorts (10 mg, 20 mg, and 30 mg) are planned. A total of 30 healthy adult participants will be enrolled, with 10 participants per cohort randomized in an 8:2 ratio of investigational product to placebo.Subjects will receive once daily administration for 7 consecutive days according to the randomization scheme.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
QUADRUPLE
Enrollment
83
Intravenous injection of KR25102 for Injection at different dose levels in SAD and MAD cohorts.
Intravenous injection of matching placebo.
The Third Xiangya Hospital, Central South University
Changsha, Hunan, China
Incidence and Severity of Adverse Events (AEs)
including vital signs, physical examination (neurological examination and injection-site examination included), 12-lead electrocardiogram, laboratory tests, abdominal ultrasonography, etc.
Time frame: From study drug administration to 15 days after the last dose
Single-Dose Pharmacokinetic (PK) Parameters
AUC₀-ₜ
Time frame: From study drug administration to 120 hours after single dose administration
Single-Dose Pharmacokinetic (PK) Parameters
AUC₀-inf
Time frame: From study drug administration to 120 hours after single dose administration
Single-Dose Pharmacokinetic (PK) Parameters
Tmax
Time frame: From study drug administration to 120 hours after single dose administration
Single-Dose Pharmacokinetic (PK) Parameters
Tlag
Time frame: From study drug administration to 120 hours after single dose administration
Single-Dose Pharmacokinetic (PK) Parameters
Cmax
Time frame: From study drug administration to 120 hours after single dose administration
Single-Dose Pharmacokinetic (PK) Parameters
t1/2
Time frame: From study drug administration to 120 hours after single dose administration
Multiple-dose Pharmacokinetic (PK) Parameters
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Cmin,ss
Time frame: From multiple-dose administration to 120 hours after the 7th dose
Multiple-dose Pharmacokinetic (PK) Parameters
Ctrough
Time frame: From multiple-dose administration to 120 hours after the 7th dose
Multiple-dose Pharmacokinetic (PK) Parameters
Cmax,ss
Time frame: From multiple-dose administration to 120 hours after the 7th dose
Multiple-dose Pharmacokinetic (PK) Parameters
Cav,ss
Time frame: From multiple-dose administration to 120 hours after the 7th dose
Multiple-dose Pharmacokinetic (PK) Parameters
AUCtau,ss
Time frame: From multiple-dose administration to 120 hours after the 7th dose
Multiple-dose Pharmacokinetic (PK) Parameters
CLss
Time frame: From multiple-dose administration to 120 hours after the 7th dose
Multiple-dose Pharmacokinetic (PK) Parameters
Tmax,ss
Time frame: From multiple-dose administration to 120 hours after the 7th dose
Multiple-dose Pharmacokinetic (PK) Parameters
t1/2,ss
Time frame: From multiple-dose administration to 120 hours after the 7th dose
QTcF Interval Changes and Correlation With Plasma Drug Concentration
Changes in QTcF interval relative to baseline (ΔQTcF), changes relative to placebo (ΔΔQTcF)
Time frame: From study drug administration to 24 hours after dosing
QTcF Interval Changes and Correlation With Plasma Drug Concentration
changes relative to placebo (ΔΔQTcF)
Time frame: From study drug administration to 24 hours after dosing