chronickidneydisease-associatedpruritus
Conditions
Interventions
Dose group 1 (0.1 µg/kg):4 subjects (of which no less than 2 were of single sex) were enrolled, 3 were randomly assigned to the experimental drug and 1 was placebo, and a single-dose intravenous infus
Dose group 2 (0.3 µg/kg):8 subjects (of which no less than 3 were of single sex) were enrolled, 6 were randomly assigned to the experimental drug and 2 were placebo, and a single-dose intravenous infu
Dose group 3 (0.5 µg/kg):8 subjects (of which no less than 3 were of single sex) were enrolled, 6 were randomly assigned to the experimental drug and 2 were placebo, and a single-dose intravenous infu
Dose group 4 (1 µg/kg):8 subjects (of which no less than 3 were of single sex) were enrolled, 6 were randomly assigned to the experimental drug and 2 were placebo, and a single-dose intravenous infusi
Dose group 5 (2 µg/kg):8 subjects (of which no less than 3 were of single sex) were enrolled, 6 were randomly assigned to the experimental drug and 2 were placebo, and a single-dose intravenous infusi
Dose group 6 (3 µg/kg):4 subjects (of which no less than 2 were of single sex) were enrolled, 3 were randomly assigned to the experimental drug and 1 was placebo, and a single-dose intravenous infusio
Sponsors
The First Affiliated Hospital, Zhejiang University School of Medicine
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: Phase Ia: Inclusion criteria 1) The subjects fully understand the purpose, nature, procedure and possible safety risks of the experiment, voluntarily act as subjects, are willing to comply with the experiment protocol, and sign informed consent before the start of any research procedure; a2) Healthy male or female aged = 18 years and = 45 years; 3) Male weight = 50.0 kg, female weight = 45.0kg; Body mass index (BMI) in the range of 19.0 ~ 26.0 kg/m2 (including the critical value); 4) The subjects (including male subjects) had no fertility plan during the trial period and within 3 months after the last dose, voluntarily adopted effective contraceptive measures, and had no sperm or egg donation plans; 5) Be able to communicate well with researchers and understand and comply with the requirements of the study. Stage Ib: Inclusion criteria 1) The subjects fully understand the purpose, nature, procedure and possible safety risks of the experiment, voluntarily act as subjects, are willing to comply with the experiment protocol, and sign informed consent before the start of any research procedure; 2) Male or female = 18 years old and = 75 years old; 3) During the screening period (the last time before randomization), the body weight after dialysis was = 40.0 kg, and the body mass index (BMI) was in the range of 16.0 ~ 30.0 kg/m2 (including the critical value); 4) Patients with end-stage renal disease received regular dialysis (including hemodialysis and hemodiafiltration) 3 times a week for 3 months before screening, and maintained a stable dialysis regimen during the study period; Note: No fewer than 4 subjects in each dose group had moderate or more moderate pruritus (at least 1 WI-NRS score = 4 during the screening period, D-1, D1 administration). 5) There were at least two single-compartment urea clearance index (spKt /V) = 1.2, or at least two urea decline rate (URR) = 65%, or one spKt /V= 1.2 and one URR= 65% on different dialysis days during the 3 months before randomization; 6) The subjects (including male subjects) had no fertility plan during the trial period and within 3 months after the last dose, voluntarily adopted effective contraceptive measures, and had no sperm or egg donation plans;
Exclusion criteria
Exclusion criteria: Phase Ia: Exclusion criteria 1) Have a history of specific allergies (such as urticaria) or are allergic (such as people who are known to be allergic to two or more drugs), or have a history of allergy to opioids, or have a history of prior allergy to this drug and related excipients (sodium chloride, acetic acid, sodium acetate, water for injection, etc.); 2) Engaged in special professionals, such as drivers, high-altitude operators, mechanical operators, operators of precision instruments; 3) Acute illness occurred within two weeks prior to screening; 4) Past or current patients with functional constipation; 5) long-term insomnia and the habit of taking sleeping pills; 6) During screening, vital signs examination, physical examination, clinical laboratory examination (blood routine, urine routine, stool routine, blood biochemistry, coagulation function, blood transfusion, thyroid function, prolactin), 12/18 lead electrocardiogram, B-ultrasound examination, and the results showed clinical significance; 7) Patients with a history of chronic or serious diseases such as cardiovascular, biliary, respiratory, blood, lymphatic, endocrine, immune, psychiatric, and neuromuscular systems within one year before screening, or patients with gastrointestinal, liver, kidney, and thyroid diseases that can affect drug absorption or metabolism within one year before screening; 8) ECG results showed prolonged QT interval (QTcF) during screening (QTcF > 450 ms in male, QTcF > 470 ms in female); 9) Have used any drugs (including any prescription, over-the-counter, herbal preparations) or health products in the 2 weeks prior to screening; 10) Any drug that inhibits or induces liver metabolism of drugs within 30 days prior to screening (e.g., inducers - barbiturates, carbamazepine, phenytoin sodium, rifampin; Inhibitors - SSRI antidepressants, cimetidine, Diltiazem, macrolides, nitroimidazoles, sedatives and hypnotics, verapamil, fluoroquinolones, antihistamines); 11) Those who ingested strong tea, caffeinated, alcoholic beverages, or chocolate, dragon fruit, mango, star fruit, guava, grapefruit, orange, grapefruit or grapefruit products within 48 hours before administration that affected drug metabolism; 12) Patients who have undergone major surgery (excluding diagnostic surgery) in the six months prior to screening, or who plan to undergo surgery during the study period, or who have undergone surgery that the investigator determines will affect drug absorption, distribution, metabolism, or excretion; 13) Those who were vaccinated within 4 weeks prior to screening (other than those who received inactivated COVID-19 vaccine), or who plan to receive any vaccine during the trial; 14) Participants who had participated in other clinical trials within 3 months prior to screening (note: the end time was defined as the date of cohort selection for the last clinical trial participation); 15) Those who have donated blood within 3 months before screening, and those whose total blood loss from blood donation or other reasons reaches or exceeds 400 mL within 6 months (excluding blood loss during female menstrual period); 16) have consumed more than 2 units of alcohol per week on average in the past year (1 unit =360 mL beer or 45 mL liquor with 40% alcohol or 150 mL wine), or have been unable to abrol during the test period, or have had an alcohol breath test result greater than 0.0 mg / 100 mL; 17) Those who smoked more than 5 cigarettes per day in t
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety and tolerability of a single dose in healthy subjects;Safety and tolerability of multiple intravenous administration over a week in hemodialysis subjects;Correlation between prolactin levels and drug exposure(hemodialysis subject); | — |
Secondary
| Measure | Time frame |
|---|---|
| Pharmacokinetic profiles were evaluated at drug concentrations at different times after a single dose in healthy subjects;The pharmacokinetic profile of hemodialysis subjects was evaluated by intravenous administration of drug concentrations at different times over a week; | — |
Countries
China
Contacts
Public ContactLiu Jian, Chen Jianghua
The First Affiliated Hospital, Zhejiang University School of Medicine
Outcome results
None listed