Study on Tolerance, Pharmacokinetics and Drug Interaction of YK-1169 in Healthy Volunteers

NCT05588531 | Completed Phase 1

• 1 other identifier: NJLBW-YK-1169
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 1

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.

Conditions

Pharmacokinetics

Keywords

YK-1169

Outcome Measures

Primary Outcomes (9)

• According to Common Terminology Criteria for Adverse Events Version 5.0, the incidence and frequency of AEs and SAEs will be statistically analyzed

  Descriptive analysis was used to calculate the incidence of adverse events and adverse reactions, and the number and frequency of occurrence of various adverse events and adverse reactions.

  Through study completion, an average of 1 month.

• clinical adverse events

  Descriptive analysis was used to analyze the relationship and outcome between the degree and duration of adverse events and the drug on a case-by-case basis

  Through study completion, an average of 1 month.

• body temperature (frontal temperature)

  Abnormal body temperature (frontal temperature) and body temperature (℃) before and after administration will be analyzed on a case-by-case basis

  Through study completion, an average of 1 month.

• Pulse

  Abnormal pulse before and after dosing will be analyzed on a case-by-case basis. Pulse (beats/min)

  Through study completion, an average of 1 month.

• sitting blood pressure

  Abnormal blood pressure before and after dosing will be analyzed on a case-by-case basis. Blood pressure (MmHg)

  Through study completion, an average of 1 month.

• physical examination

  Abnormalities before and after administration of physical examination were analyzed on a case-by-case basis

  Through study completion, an average of 1 month.

• laboratory tests

  Abnormalities before and after administration in laboratory tests were analyzed on a case-by-case basis

  Through study completion, an average of 1 month.

• 12-lead ECG

  Abnormalities before and after 12-lead ECG administration were analyzed on a case-by-case basis

  Through study completion, an average of 1 month.

• premature withdrawal

  Analysis of early withdrawals on a case-by-case basis

  Through study completion, an average of 1 month.

Secondary Outcomes (14)

• The main pharmacokinetic parameters evaluated in the single-dose and drug-drug interaction studies included: Cmax

  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

• The main pharmacokinetic parameters evaluated in the single-dose and drug-drug interaction studies included: Tmax

  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

• The main pharmacokinetic parameters evaluated in the single-dose and drug-drug interaction studies included: AUC

  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

• The main pharmacokinetic parameters evaluated in the single-dose and drug-drug interaction studies included: t1/2

  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

• The main pharmacokinetic parameters evaluated in the single-dose and drug-drug interaction studies included: CL

  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

Study Arms (6)

YK-1169 0.5g (containing cefepime 0.4g, avibactam 0.1g)

ACTIVE COMPARATOR

Four healthy subjects in group A1, two males and two females, without control, were administered the test drug

Drug: Group 1:YK-1169

YK-1169 1.25 g (containing cefepime 1.0 g and avibactam 0.25 g)

ACTIVE COMPARATOR

12 healthy subjects, of whom 10 subjects were administered the investigational product and 2 subjects were administered placebo, half males and half females

Drug: Group 2:YK-1169/Placebo Injection

YK-1169 2.5g (containing cefepime 2.0g and avibactam 0.5g)

ACTIVE COMPARATOR

12 healthy subjects, of whom 10 subjects were administered the investigational product and 2 subjects were administered placebo, half males and half females

Drug: Group 3:YK-1169/Placebo

YK-1169 3.75g (containing cefepime 3.0g and avibactam 0.75g)

PLACEBO COMPARATOR

12 healthy subjects, of whom 10 subjects were administered the investigational product and 2 subjects were administered placebo, half males and half females

Drug: Group 4:YK-1169/Placebo

YK-1169 5.0g (containing cefepime 4.0g and avibactam 1.0g)

ACTIVE COMPARATOR

8 healthy subjects, 6 of whom were administered the investigational product and 2 of whom were administered placebo, half males and half females

Drug: Group 5:YK-1169/Placebo Injection

Drug Interaction Studies

ACTIVE COMPARATOR

18 subjects (single gender not less than 1/3) were randomly divided into D1, D2 and D3 groups, 6 subjects for each group

Drug: Group 1:YK-1169; Drug: Group 6:YK-1169/Cefepime hydrochloride for injection/Avibactam for injection

Interventions

Group 1:YK-1169 DRUG

YK-1169 0.5g (containing cefepime 0.4g, avibactam 0.1g) single intravenous infusion for 2 hours

Drug Interaction Studies; YK-1169 0.5g (containing cefepime 0.4g, avibactam 0.1g)

Group 2:YK-1169/Placebo Injection DRUG

YK-1169 1.25g (containing cefepime 1.0g, avibactam 0.25g) / placebo single intravenous infusion for 2 hours

YK-1169 1.25 g (containing cefepime 1.0 g and avibactam 0.25 g)

Group 3:YK-1169/Placebo DRUG

On the first day, YK-1169 2.5 g (containing cefepime 2.0 g, avibactam 0.5g) was single intravenously infused for 2 h. On the third day, YK-1169 2.5 g (containing cefepime 2.0 g, avibactam 0.5g) was single intravenous infusion for 2 h, three times a day at 8-h intervals, until the morning dose on the tenth day

YK-1169 2.5g (containing cefepime 2.0g and avibactam 0.5g)

Group 4:YK-1169/Placebo DRUG

On the first day, YK-1169 3.75 g (containing cefepime 3.0 g, avibactam 0.75g) was single intravenously infused for 2 h. On the third day, YK-1169 3.75 g (containing cefepime 3.0 g, avibactam 0.75g) was single intravenous infusion for 2 h, three times a day at 8-h intervals, until the morning dose on the tenth day

YK-1169 3.75g (containing cefepime 3.0g and avibactam 0.75g)

Group 5:YK-1169/Placebo Injection DRUG

YK-1169 5.0g (containing cefepime 4.0g, avibactam 1.0g) / placebo single intravenous infusion for 2 hours

YK-1169 5.0g (containing cefepime 4.0g and avibactam 1.0g)

Group 6:YK-1169/Cefepime hydrochloride for injection/Avibactam for injection DRUG

YK-1169 2.5g (containing cefepime 2.0g, avibactam 0.5g)/cefepime hydrochloride for injection 2.0g/avibactam for injection 0.5g, three-cycle three-cross single intravenous infusion for 2 hours

Drug Interaction Studies

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• healthy subjects aged 18 to 45 years (including the cut-off value), both men and women;
• body mass index (BMI) 19.0-28.0 kg/m2 (including the cut-off value);
• 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;
• be able to communicate well with the investigator, and understand and abide by the requirements of this study.

You may not qualify if:

• participate in any drug clinical trials or use of study drugs within 3 months before the use of study drugs;
• 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;
• 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;
• can not tolerate intravenous puncture or have a history of halo, fainting needle;
• 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; -
• Use of any drugs (including Chinese herbal medicine, health products, etc.) within 14 days before the use of the study drug;
• Vaccination or live attenuated vaccine within 14 days before the use of the study drug, or plan to vaccinate during the trial;
• 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;
• 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;
• 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;
• habitual drinking, tea, coffee and/or caffeine-containing beverages and do not agree to stop eating the above diet during the trial;
• special requirements for diet, can not comply with the unified diet, or lactose intolerance;
• 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.);
• 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);
• \. 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.

Sponsors & Collaborators

• Nanjing Yoko Biomedical Co., Ltd.: lead

Study Sites (1)

辛玉霞

Nanjing, Jiangsu, 210000, China

Location

MeSH Terms

Interventions

Injections; avibactam

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: FACTORIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The whole trial is conducted by dose escalation from low to high.

Study Record Dates

• First Submitted: August 19, 2022
• First Posted: October 20, 2022
• Study Start: December 20, 2021
• Primary Completion: April 2, 2022
• Study Completion: April 8, 2022
• Last Updated: October 20, 2022

Record last verified: 2022-10

Locations

CN (1)