This is a Phase 1a, double-blind, randomized, placebo- controlled, SAD study to assess safety, tolerability, PK, and PD of TU7710 in warfarin treated healthy male participants.
The 40 subjects will be divided into 5 cohorts, and the subjects assigned to each cohort will be randomly assigned with 6 persons receiving TU7710 and 2 persons receiving a placebo for TU7710. Each cohort will proceed in sequence and the next cohort study will be decided by the Safety Monitoring Committee (SMC) . Subjects will be participated in the study after warfarin anti-coagulation to maintain the INR between 2.00 and 3.00 as a preventive measure for potential thrombosis prior to the IP administration.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
40
In each dose level, 6 subjects will be assigned to TU7710. Anticipated escalating dose levels are 100mcg/kg, 200mcg/kg, 400mcg/kg, 800mcg/kg and the last dose will be decided after assessing cohort 1\~4 PK, PD, safety, and exploratory efficacy data.
Placebo of TU7710 at corresponding TU7710 dose level. In each dose level, 2 subjects will be assigned to placebo group.
Seoul National University Hospital
Seoul, South Korea
Number and proportion of participants with adverse events
Number and proportion of participants with adverse events/ adverse reaction /SAE overall and by treatment group
Time frame: 30 days post-dose
Number of subjects with significant abnormal laboratory values
Mean with standard deviation, median, maximum, minimum results of laboratory values in each treatment group. The laboratory parameters that will be assessed are clinical chemistry, hematology and urinalysis.
Time frame: 30 days post-dose
ADA and Neutralizing antibody results
Incidence of subjects with ADA and Nab positive results
Time frame: 30 days post-dose
Number of subjects with significant abnormal Electrocardiography (ECG) findings
Mean with standard deviation, median, maximum, minimum results of ECG results in each treatment group. The ECG parameters that will be assessed are heart rate, PR interval, QRS interval, QT interval, and QTcF interval.
Time frame: 30 days post-dose
Number of subjects With Significant Abnormal vital sign findings
Mean with standard deviation, median, maximum, minimum results of vital sign values in each treatment group. The vital signs that will be assessed are body temperature, pulse rate, respiratory rate, and systolic and diastolic blood pressure.
Time frame: 30 days post-dose
Pharmacokinetics assessment_Maximum concentration
Maximum plasma VIIa activity level in each dose level
Time frame: 4 days post-dose
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Pharmacokinetics assessment_AUC last
Area under plasma activity-time curve after TU7710 single administration from time zero to last quantifiable concentration
Time frame: 4 days post-dose
Pharmacokinetics assessment_AUC inf
Area Under the Plasma activity-time curve after TU7710 single administration From Time Zero Extrapolated to Infinity
Time frame: 4 days post-dose
Pharmacokinetics assessment_Clearance
Clearance after TU7710 single administration
Time frame: 4 days post-dose
Pharmacokinetics assessment_Volume of distribution
Volume of distribution after TU7710 single administration
Time frame: 4 days post-dose
Pharmacokinetics assessment_Dose proportionality
Regression analysis using the power model between the log-converted Cmax, AUClast, and the log-converted dose can be performed, and each parameter adjusted by dose can be calculated and compared between the dose groups
Time frame: 4 days post-dose
Pharmacokinetics assessment_Tmax
Time from administration to maximum plasma VIIa level in each dose level
Time frame: 4 days post-dose
Pharmacodynamic assessment_INR change from baseline
INR measurement change from baseline to day 5 in each treatment group and dose level
Time frame: 5 days post-dose
Pharmacodynamic assessment_PT change from baseline
PT measurement change from baseline to day 5 in each treatment group and dose level
Time frame: 5 days post-dose
Pharmacodynamic assessment_aPTT change from baseline
aPTT measurement change from baseline to day 5 in each treatment group and dose level
Time frame: 5 days post-dose
Pharmacokinetics assessment_incremental recovery
Incremental recovery after TU7710 single administration expressed as the ratio of measured peak level against dose per bodyweight
Time frame: 4 days post-dose