Clinical trial NCT05588531: Study on Tolerance, Pharmacokinetics and Drug Interaction of YK-1169 in Healthy Volunteers
Official title: Study on Tolerance, Pharmacokinetics and Drug Interaction of YK-1169 in Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Pharmacokinetics
Keywords: YK-1169
Lead sponsor: Nanjing Yoko Biomedical Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2022-10-20
Enrollment: 66
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Intervention model description: The whole trial is conducted by dose escalation from low to high.
Primary purpose: BASIC_SCIENCE

Brief summary: To evaluate the safety and tolerability of multiple doses of YK-1169 in healthy subjects, the pharmacokinetic characteristics of multiple doses in healthy subjects, and the drug interaction between cefepime and avibactam.

Detailed description: A randomized, single-blind, placebo-controlled, dose-escalation, single-center clinical trial design was used. A total of 5 dose groups A1, A2, A3, A4 and A5 were set in the test, including A1 YK-1169 0.5g group (containing cefepime 0.4g and avibactam 0.1g), A2 YK-1169 1.25g group (containing cefepime 1.0g and avibactam 0.25g), A3 YK-1169 2.5g (containing cefepime 2.0g and avibactam 0.5g), A4 YK-1169 3.75g (containing cefepime 3.0g and avibactam 0.75g) and A5 YK-1169 5.0g (containing cefepime 4.0g and avibactam 1.0g).

A single-center, randomized, open, three-period three-crossover 3 × 3 Latin square trial design was used. To study the effect of intravenous infusion of this product, cefepime for injection or avibactam for injection on the disposition process of the drug in the human body, so as to study whether there is a pharmacokinetic drug interaction in this product.

Eligibility criteria: Inclusion Criteria:

1. healthy subjects aged 18 to 45 years (including the cut-off value), both men and women;
2. body mass index (BMI) 19.0-28.0 kg/m2 (including the cut-off value);
3. fully understand the purpose of the trial, basically understand the pharmacological effects of the investigational drug and possible risks, voluntarily sign the informed consent form;
4. be able to communicate well with the investigator, and understand and abide by the requirements of this study.

Exclusion Criteria:

1. participate in any drug clinical trials or use of study drugs within 3 months before the use of study drugs;
2. have a history of respiratory system, digestive system, cardiovascular system, endocrine system, urinary system, nervous system (such as epilepsy, etc.), hematology, immunology (including personal or family history of hereditary immunodeficiency), metabolic abnormalities and the investigator believes that there is still clinical significance;
3. allergic to penicillins, allergic to cephalosporins, allergic to amoxicillin clavulanate potassium tablets or their excipients, or a history of drug, food or other substance allergy;
4. can not tolerate intravenous puncture or have a history of halo, fainting needle;
5. received surgery within 6 months before the use of study drugs that will affect drug distribution, metabolism, excretion; or received surgery within 4 weeks before the use of study drugs; or plan to undergo surgery during the study period; -
6. Use of any drugs (including Chinese herbal medicine, health products, etc.) within 14 days before the use of the study drug;
7. Vaccination or live attenuated vaccine within 14 days before the use of the study drug, or plan to vaccinate during the trial;
8. Blood donation or massive blood loss (\> 400 mL) within 3 months before the use of the study drug, receiving blood transfusion or use of blood products, or intend to donate blood or blood components during the trial or within 3 months after the end of the trial;
9. Drug abusers or use of soft drugs (such as marijuana) or hard drugs (such as cocaine, phencyclidine, etc.) within 1 year before the use of the study drug;
10. Smokers or smokers who smoke more than 5 cigarettes per day for 3 months before the use of the study drug, or can not stop using any tobacco products during the trial;
11. habitual drinking, tea, coffee and/or caffeine-containing beverages and do not agree to stop eating the above diet during the trial;
12. special requirements for diet, can not comply with the unified diet, or lactose intolerance;
13. volunteers (or their partners) during the trial to 3 months after the end of the trial have a pregnancy plan, sperm donation and egg donation plan, or reluctant to take one or more non-drug contraceptive measures (such as complete abstinence, condoms, contraceptive rings, partner ligation, etc.);
14. female volunteers are pregnant or lactating women; or have non-protective sex within 2 weeks before the use of the study drug; or use oral contraceptives within 30 days before the use of the study drug or use of long-acting estrogen or progestogen injection or implants within 6 months before the use of the study drug; 15. physical examination, 12-lead electrocardiogram, vital signs, abdominal ultrasound, chest X-ray, laboratory tests are abnormal clinical significance (subject to the clinician 's judgment);

16. Volunteers may not be able to complete this study for other reasons or have other reasons for not being suitable for the trial judged by the investigator; 17. First cycle admission examination vital signs abnormal clinical significance, drug screening positive, alcohol test positive or female pregnancy test abnormal clinical significance.

Primary outcomes:
measure: According to Common Terminology Criteria for Adverse Events Version 5.0, the incidence and frequency of AEs and SAEs will be statistically analyzed
timeFrame: Through study completion, an average of 1 month.
measure: clinical adverse events
timeFrame: Through study completion, an average of 1 month.
measure: body temperature (frontal temperature)
timeFrame: Through study completion, an average of 1 month.
measure: Pulse
timeFrame: Through study completion, an average of 1 month.
measure: sitting blood pressure
timeFrame: Through study completion, an average of 1 month.
measure: physical examination
timeFrame: Through study completion, an average of 1 month.
measure: laboratory tests
timeFrame: Through study completion, an average of 1 month.
measure: 12-lead ECG
timeFrame: Through study completion, an average of 1 month.
measure: premature withdrawal
timeFrame: Through study completion, an average of 1 month.
Secondary outcomes:
measure: The main pharmacokinetic parameters evaluated in the single-dose and drug-drug interaction studies included: Cmax
timeFrame: Single dose: within 1 hour before to 24 hours after dosing on Day 1.Drug Interactions: Within 1 hour prior to dosing on Day 1 through 24 hours postdose of each cycle
measure: The main pharmacokinetic parameters evaluated in the single-dose and drug-drug interaction studies included: Tmax
timeFrame: Single dose: within 1 hour before to 24 hours after dosing on Day 1.Drug Interactions: Within 1 hour prior to dosing on Day 1 through 24 hours postdose of each cycle
measure: The main pharmacokinetic parameters evaluated in the single-dose and drug-drug interaction studies included: AUC
timeFrame: Single dose: within 1 hour before to 24 hours after dosing on Day 1.Drug Interactions: Within 1 hour prior to dosing on Day 1 through 24 hours postdose of each cycle
measure: The main pharmacokinetic parameters evaluated in the single-dose and drug-drug interaction studies included: t1/2
timeFrame: Single dose: within 1 hour before to 24 hours after dosing on Day 1.Drug Interactions: Within 1 hour prior to dosing on Day 1 through 24 hours postdose of each cycle
measure: The main pharmacokinetic parameters evaluated in the single-dose and drug-drug interaction studies included: CL
timeFrame: Single dose: within 1 hour before to 24 hours after dosing on Day 1.Drug Interactions: Within 1 hour prior to dosing on Day 1 through 24 hours postdose of each cycle
measure: The main pharmacokinetic parameters evaluated in the single-dose and drug-drug interaction studies included: VZ
timeFrame: Single dose: within 1 hour before to 24 hours after dosing on Day 1.Drug Interactions: Within 1 hour prior to dosing on Day 1 through 24 hours postdose of each cycle
measure: The main pharmacokinetic parameters evaluated in the single-dose and drug-drug interaction studies included: λz
timeFrame: Single dose: within 1 hour before to 24 hours after dosing on Day 1.Drug Interactions: Within 1 hour prior to dosing on Day 1 through 24 hours postdose of each cycle
measure: Cumulative urinary excretion ratio, etc. in 2.5 g single dose group of YK-1169
timeFrame: Single dose: within 1 hour before to 24 hours after dosing on Day 1
measure: Main pharmacokinetic parameters evaluated in multiple dose studies included: C min, ss
timeFrame: Multiple dose: within 1 hour before dosing on Day 1 to D9 (24 hours after dosing on D8).
measure: Main pharmacokinetic parameters evaluated in multiple dose studies included: C max,ss
timeFrame: Multiple dose: within 1 hour before dosing on Day 1 to D9 (24 hours after dosing on D8).
measure: Main pharmacokinetic parameters evaluated in multiple dose studies included: Tmax,ss
timeFrame: Multiple dose: within 1 hour before dosing on Day 1 to D9 (24 hours after dosing on D8).
measure: Main pharmacokinetic parameters evaluated in multiple dose studies included:AUC
timeFrame: Multiple dose: within 1 hour before dosing on Day 1 to D9 (24 hours after dosing on D8).
measure: Main pharmacokinetic parameters evaluated in multiple dose studies included:Cav,ss
timeFrame: Multiple dose: within 1 hour before dosing on Day 1 to D9 (24 hours after dosing on D8).
measure: Main pharmacokinetic parameters evaluated in multiple dose studies included:t1/2
timeFrame: Multiple dose: within 1 hour before dosing on Day 1 to D9 (24 hours after dosing on D8).
Other outcomes:
Locations:
city: Nanjing
country: China
facility: 辛玉霞
state: Jiangsu
Study officials:
References: