The main purpose To evaluate the safety and tolerability of pegloticase in subjects with asymptomatic hyperuricemia by single intravenous infusion at different doses, and to provide a basis for multiple doses of Pegloticase in subjects with asymptomatic hyperuricemia. A secondary purpose To evaluate the pharmacokinetics, pharmacodynamics and immunogenicity of Pegloticase with single-pass intravenous drip in subjects with asymptomatic hyperuricemia. Exploratory purpose Plasma uricase activity (pUox) analysis of pegloticase with single-pass intravenous drip in subjects with asymptomatic hyperuricemia.
To evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics analysis of pegloticase in subjects with asymptomatic hyperuricemia. This is a phase I randomized, double-blind, placebo-controlled and dose-increasing single dosing study. Five dose groups of 1, 2, 4, 8 or 12 mg were planned to explore the most appropriate dose and to provide a basis for multiple doses of Pegloticase in subjects with asymptomatic hyperuricemia.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
45
SIBP-R002: injection; strength: 1, 2, 4, 8 or 12 mg; dose escalation and the first group is 1mg (intravenous infusion, 5 groups, the first group consisted of four people, and the other groups consisted of eight).
Intravenous infusion, 5mg or 1\~2mg/kg. These were administered within 30 minutes prior to infusion of the experimental drug.
10mg, intramuscular injection.These were administered within 30 minutes prior to infusion of the experimental drug.
The same volume of placebo as SIBP-R002: injection; strength: the same volume of placebo as SIBP-R002 of 1, 2, 4, 8 or 12 mg (intravenous infusion, 5 groups, the first group consisted of one people, and the other groups consisted of two). The rule and dose of placebo were the same as SIBP-R002.
The first affiliated hospital of Bengbu medical college
Bengbu, Anhui, China
The number of any adverse events (AE)
All subjects were observed during the trial for any AE that occurred during the clinical study, including clinical symptoms and life abnormal physical signs, abnormalities in electrocardiogram and laboratory tests. Attention should be paid to the occurrence of AE related to infusion reaction, allergic reaction, vomiting and watery stools/loose stools, acute attack of gout, cardiovascular adverse events and so on.
Time frame: 35 days after the last dose
The number of serious adverse events (SAE)
That is serious adverse events, any serious adverse events that occurred to the subject during the study period.
Time frame: 35 days after the last dose
AUC 0-t (Area Under The Plasma Concentration Versus Time Curve)
Area under the blood concentration-time curve from 0 to T. It shows the degree to which a drug is absorbed and used in the body.
Time frame: 35 days after the last dose
Cmax(Peak Plasma Concentration)
It shows the highest plasma concentration of a drug that can be achieved after administration.
Time frame: 35 days after the last dose
AUC inf (Area Under The Plasma Concentration Versus Time Curve)
Area under the blood concentration-time curve from 0 to unlimited time. It shows the degree to which a drug is absorbed and used in the body.
Time frame: 35 days after the last dose
Tmax(Peak Time)
That is peak time of drug action, it shows the time required to reach the maximum concentration on the subject plasma concentration curve after administration.
Time frame: 35 days after the last dose
T ½(Terminal elimination half-life)
It reflects how quickly the drug is eliminated from the body.
Time frame: 35 days after the last dose
CL(Clearance Rate)
Apparent volume of drug distribution removed from the body per unit time.
Time frame: 35 days after the last dose
The uric acid to creatinine ratio in Urine
To evaluate the effect of single use of peruricase on uric acid to creatinine ratio (UAc:Cr) in 24h urine of patients with hyperuricemia.
Time frame: 35 days after the last dose
Vd(Apparent volume of distribution)
Apparent volume of distribution refers to the ratio of the amount of drug in vivo to the concentration of drug in blood when a drug reaches dynamic equilibrium in the body. It is a widely used parameters for drug distribution.
Time frame: 35 days after the last dose
λz
Elimination rate constant of a drug.It is a common pharmacokinetic indicator.
Time frame: 35 days after the last dose
The positive rate of anti-uricase antibody
An evaluation index of immunogenicity of an experimental drug. If detected, it is positive.
Time frame: 35 days after the last dose
The positive rate of anti-PEG antibody
An evaluation index of immunogenicity of an experimental drug. If detected, it is positive.
Time frame: 35 days after the last dose
The positive rate of anti-PEG-uricase antibody
An evaluation index of immunogenicity of an experimental drug. If detected, it is positive.
Time frame: 35 days after the last dose
Antibody titer of anti-uricase antibody
An evaluation index of immunogenicity of an experimental drug.
Time frame: 35 days after the last dose
Antibody titer of anti-PEG Antibody
An evaluation index of immunogenicity of an experimental drug.
Time frame: 35 days after the last dose
Antibody titer of anti-PEG-uricase Antibody
An evaluation index of immunogenicity of an experimental drug.
Time frame: 35 days after the last dose
Positive rate of neutralizing antibody(NAb)
NAb positive rate was assessed by detecting neutralizing antibodies in blood samples.
Time frame: 35 days after the last dose
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