A Phase 1 Study of YZJ-4729 Tartrate Injection in Healthy Chinese Subjects

NCT06681493 | Completed Phase 1

• 1 other identifier: YZJ-4729-1-01
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 1

Brief Summary

Part A Primary objective:

• To evaluate the safety, tolerability, and pharmacokinetic profile of a single dose of YZJ-4729 tartrate injection. Secondary objectives:
• To investigate the PK/PD profile of YZJ-4729 tartrate injection administered as a single dose;
• To investigate the metabolic transformation characteristics of YZJ-4729 tartrate;
• To assess the relationship between plasma concentrations and change in QT interval (C-QT) and the effect on QT interval in subjects after a single dose of YZJ-4729 tartrate injection. Part B Primary objective:
• To evaluate the safety, tolerability and pharmacokinetic profile of YZJ-4729 tartrate injection administered at the same dose and at different infusion rates . Secondary objectives:
• To investigate the PK/PD profile of YZJ-4729 tartrate injection administered at the same dose and at different infusion rates.

Conditions

Postoperative Analgesia

Outcome Measures

Primary Outcomes (15)

• Incidence of adverse events (AEs) and serious adverse events (SAEs)

  Part A： From Day 1 to Day 5 Part B： From Day 1 to Day 17

• Incidence of participants with clinical laboratory abnormalities

  Part A： From Day 1 to Day 5 Part B： From Day 1 to Day 17

• Incidence of participants with vital signs abnormalities

  Part A： From Day 1 to Day 5 Part B： From Day 1 to Day 17

• Incidence of participants with physical exam abnormalities

  Part A： From Day 1 to Day 5 Part B： From Day 1 to Day 17

• Cmax

  Cmax is defined as the observed maximum plasma concentration.

  Pre-dose to 72h post-dose

• AUCinf

  AUCinf is defined as the area under the plasma concentration-time curve extrapolated to infinity from time zero.

  Pre-dose to 72h post-dose

• AUC0-24h

  AUC0-24h is defined as the area under the plasma concentration-time curve from time zero to 24h.

  Pre-dose to 72h post-dose

• AUC0-t

  AUC0-24h is defined as the area under the plasma concentration-time curve from time zero to the last observable concentration.

  Pre-dose to 72h post-dose

• t1/2z

  t1/2z is defined as the elimination half-life.

  Pre-dose to 72h post-dose

• Tmax

  Tmax is defined as the observed time to reach Cmax.

  Pre-dose to 72h post-dose

• CL

  CL is defined as the clearance.

  Pre-dose to 72h post-dose

• Vz

  V is defined as the apparent volume of distribution.

  Pre-dose to 72h post-dose

• MRT

  MRT is defined as the mean residence time.

  Pre-dose to 72h post-dose

• Ae0-t

  Ae0-t is defined as the cumulative amount of drug excreted in urine or fecal from time zero to the last observable concentration.

  Pre-dose to 72h post-dose

• Cumulative excretion percentage of drug through urine and feces

  Pre-dose to 72h post-dose

Secondary Outcomes (2)

• Pupil diameter

  Pre-dose to 12h post-dose

• Change from baseline of QTcF by timepoint

  Pre-dose to 24h post-dose

Study Arms (2)

Part A

EXPERIMENTAL

Part A Experimental: YZJ-4729 Tartrate injection; Part A Control: YZJ-4729 simulated injection

Drug: YZJ-4729 Tartrate injection; Drug: YZJ-4729 simulated injection

Part B

EXPERIMENTAL

Subjects will receive YZJ-4729 Tartrate injection

Drug: YZJ-4729 Tartrate injection

Interventions

YZJ-4729 Tartrate injection DRUG

Infusion, QD

Part A; Part B

YZJ-4729 simulated injection DRUG

Infusion, QD

Part A

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Male or female subjects aged between 18 and 45 years (inclusive) on the day of signing the informed consent;
• Male subjects weighing no less than 50 kg and female subjects weighing no less than 45 kg. Body mass index within the range 19.0-26.0 kg/m 2 (inclusive);
• Subjects in good health without a history of serious diseases and chronic diseases such as respiratory system, circulatory system, digestive system, urinary system, blood system, endocrine system, immune system, nervous system and mental system;
• From the date of signing the informed consent form until 6 months after the last dose of investigational drug, the subject (including partner) need to have no sperm or egg donation plan or pregnancy plan and voluntarily take effective contraceptive measures.
• Voluntarily need to sign the informed consent form before the trial, and fully understand the content, process and possible adverse reactions of the trial.

You may not qualify if:

• Medical history of cardiovascular and respiratory system (such as sleep apnea syndrome, pulmonary heart disease or chronic bronchial asthma), liver, kidney, nervous system (such as epilepsy), blood system or mental disorders that the researcher considers clinically significant;
• Medical history of cardiovascular system disease, including but not limited to history or family history of syncope, coronary heart disease (such as coronary angiography diagnosis of coronary heart disease, history of acute coronary syndrome, history of myocardial infarction, etc.), valvular heart disease, heart failure, history of non-drug-induced bradyarrhythmia, frequent ventricular premature beats, ventricular tachycardia, etc.; or previous QTc prolongation or other risk factors for torsades de pointes (hypokalemia, etc.), or a family history of a first-degree relative (i.e., biological parent, brother, sister or child) with short QT syndrome, long QT syndrome, sudden death of unknown cause in his youth (less than/equal to 40 years old), drowning or sudden infant death syndrome;
• Medical history of symptomatic head trauma;
• History of frequent nausea or vomiting of any etiology;
• Medical history of glaucoma or any condition affecting pupil size;
• Major surgery or major trauma within 6 months prior to screening or planning to undergo surgery during the study;
• Known to be allergic to two or more kinds of food and drugs;
• Known to be allergic to opioids, or have contraindications for the use of such drugs;
• Difficulties in collecting venous blood, or the cases with known needle and blood sickness history;
• Female subjects who are lactating, pregnant, preparing for pregnancy or have the abnormal pregnancy test results with clinical significance at screening;
• Clinically significant abnormal ECG findings at screening, such as QTcF ≥ 450 ms in men and QTcF ≥ 470 ms in women; PR interval ≥ 200 ms; QRS complex duration ≥ 120 ms;
• Abnormal vital signs at screening (systolic blood pressure \< 90 mmHg or \> 140 mmHg, diastolic blood pressure \< 50 mmHg or \> 90 mmHg; respiratory \< 16 breaths/min or \> 20 breaths/min; pulse \< 60 beats/min or \>100 beats/min) or clinically significant abnormal physical examination, laboratory tests (blood routine, urine routine, blood biochemistry, coagulation function), chest anteroposterior view or CT, abdominal color ultrasound (subject to the judgment of clinicians);
• Subjects having clinically significant abnormalities in any of hepatitis B virus surface antigen, Treponema pallidum-specific antibody, human immunodeficiency virus antibody and hepatitis C virus antibody at screening;
• Serum potassium, magnesium and calcium exceeding the upper limit of normal reference range or lower limit of normal reference range at screening;
• Oxygen saturation less than 95% at screening;

Sponsors & Collaborators

• Shanghai Haiyan Pharmaceutical Technology Co., Ltd.: lead

Study Sites (1)

Xiangya Third Hospital, Central South University

Changsha, China

Location

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 31, 2024
• First Posted: November 8, 2024
• Study Start: October 12, 2022
• Primary Completion: April 14, 2023
• Study Completion: September 22, 2023
• Last Updated: November 8, 2024

Record last verified: 2024-11

Locations

CN (1)