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

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

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.

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.