Tolerance, Pharmacokinetics / Pharmacodynamics (PK / PD) and Immunogenicity of Pegylated Uric Acid Oxidase for Injection in Healthy Adults and Hyperuricemia Volunteers

Study Overview
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Brief Summary
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A randomized, double-blind, placebo-controlled study of tolerance, pharmacokinetic / pharmacodynamics (PK / PD) and immunogenicity of single administration of PEG uric oxidase for injection in healthy adults and hyperuricemia volunteers.

Official Title
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A Randomized, Double-blind, Placebo-controlled Study to Evaluate the Tolerance, Pharmacokinetics / Pharmacodynamics (PK / PD) and Immunogenicity of Pegylated Uric Acid Oxidase for Injection in Healthy Adults and Hyperuricemia Volunteers

Conditions
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Hyperuricemia

Intervention / Treatment
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* Drug: Polyglycol lated urate oxidase for injection
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy volunteers: Subjects understand well trial purpose, nature, content, process and possible adverse reactions, and voluntarily sign an informed consent form. Serum uric acid level<360 µ mol / L twice on different days. Healthy male or female aged between 18 and 60 years old (including the critical value). The body mass index is in the range of 18-30kg/m2 (including the critical value). The weight of male is not less than 50 kg, and that of female is not less than 45 kg (including the critical value). Subjects who had not any medical history of cardiovascular, digestive, respiratory, nervous, haemal diseases or hepatic/renal impairment.The following examination show that the indicators are normal or abnormal without clinical significance. The examination including: physical examination, 12-lead ECG, vital sign measurements and laboratory safety tests . The subjects have no family planning within 6 months and could select contraceptive method. They have no sperm and egg donation program. Before the study, all subjects have been informed of the study's purpose, protocal, benefits, and risks, and signed the informed consent voluntarily. The blood pregnancy test of female subjects was negative, the menstrual cycle was regular, and the menstrual bleeding period was 3   7 days. Patients with hyperuricemia: Patients with hyperuricemia ,male or female aged between 18 and 60 years old (including the critical value). Stop uric acid lowering treatment for at least 7 days, and 480≤UA≤540µmol/L twice on different days within 7 days. The body mass index is in the range of 18-30kg/m2 (including the critical value). The weight of male is not less than 50 kg, and that of female is not less than 45 kg (including the critical value). Before the study, all subjects have been informed of the study's purpose, protocal, benefits, and risks, and signed the informed consent voluntarily. The blood pregnancy test of female subjects was negative, the menstrual cycle was regular, and the menstrual bleeding period was 3   7 days. Exclusion Criteria: Healthy volunteers: A history of drug allergy, or allergic allergic disease, or known to be allergic to the test drug or its excipients or the same type of drug; Hepatitis (including hepatitis B and C), positive screening results for AIDS or syphilis; Any history of acute or chronic illness that might affect drug absorption, and/or metabolism; Any history of drug abuse in the past 12 months prior to screening; Any history of alcohol abuse 3 months prior to screening or moderate drinkers (drink more 2 units per day or 14 units per week); Smoking more than 5 cigarettes per day during the 3 months prior to screening; Blood donation, massive blood loss (#400mL) or enrolled in other clinical trials 3 months prior to screening; Any use of other prescription drugs (including contraceptive)#over-the counter drugs, Chinese herbal medicine, health care products and 14 days prior to medication for this study; Any history of postural hypotension, syncope, or amaurosis; 6-glucose phosphate dehydrogenase (G6PD) deficiency; Lactating or pregnant women Patients with hyperuricemia: Using uric acid lowering drugs and unwilling to stop existing drugs. Ultrasonic examination of the metatarsal-toe joint suggested the presence of tophi. Serum CA72-4 level ≥7.5U / mL. History of organic heart disease (symptomatic cardiac insufficiency with grade II-IV). Patients with refractory hypertension. Patients with malignant tumors (treatment or not). Patients with organ transplantation treated with immunosuppressants. Any history of drug abuse in the past 12 months prior to screening; Any history of alcohol abuse 3 months prior to screening or moderate drinkers (drink more 2 units per day or 14 units per week). Smoking more than 5 cigarettes per day during the 3 months prior to screening. A history of drug allergy, or allergic allergic disease, or known to be allergic to the test drug or its excipients or the same type of drug. Any history of acute or chronic illness that might affect drug absorption, and/or metabolism. 6-glucose phosphate dehydrogenase (G6PD) deficiency. Once treated with urate oxidase. Subjects had an uncorrected dehydration, acidosis, hypotension, renal insufficiency, or were using drugs with nephrotoxicity.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PEGylated Urate Oxidase for Injection<br>PEGylated Urate Oxidase for Injection，specification:5mg，Single dose ascending.Healthy subjects were divided into three dose groups (0.5mg, 1mg, 2mg), and hyperuricemia patients were divided into four dose groups (2mg, 4mg, 8mg, 12 mg), with increasing dose design.Each group will receive the experimental drug in 6 subjects. | Drug: Polyglycol lated urate oxidase for injection<br>* Single dose escalation<br>|
| Placebo Comparator: Placebo<br>Placebo , specification: 5mg,Single dose. Groups received the placebo in 2 patients per group. | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak Plasma Concentration (Cmax) | Evaluation of Peak Plasma Concentration (Cmax) | 500 days | 
| Maximum tolerated dose Maximum tolerated dose | Maximum tolerated dose Maximum tolerated dose for a single dose | 500 days | 
| Area under the plasma concentration versus time curve (AUC)0-t | Evaluation of Area under the plasma concentration versus time curve (AUC)0-t | 500 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence rate of Adverse Events | Adverse events were recorded to evaluate the safety of the studied drugs | 500 day | 
| Immunogenicity | Antidrug antibody detection | 500day |