PK/PD Study of YZJ-1139

A Randomized, Double-Blind, Zolpidem and Placebo-Controlled, 4-Way-Period Crossover, Pharmacokinetics and Pharmacodynamics Study of YZJ-1139 Single-Dose Oral in Healthy Young and Elderly Chinese Subjects

Primary Objective： To determine the dose-response relationship of YZJ-1139 in young and elderly Chinese subjects after a single oral administration of different doses, and to compare it with zolpidem at clinical doses.

Secondary Objective: To investigate the safety and tolerability of YZJ-1139 in young and elderly Chinese subjects after a single oral administration of different doses, and to compare it with zolpidem at clinical doses.

Study Overview

• Status: Completed
• Conditions: Insomnia
• Intervention / Treatment: Drug: Placebo; Drug: YZJ-1139; Drug: Zolpidem

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing, China
    • Beijing Tiantan Hospital, Capital Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Young adults and elderly Chinese healthy subjects, both male and female;
2. Age: [young adult group] 18-45 years old (including the threshold value); [Elderly group]65~75 years old (including the cut-off value);
3. Body weight [only for young adults]: ≥50kg, BMI: 18~28kg/m2 (including the threshold value);
4. Understand and sign the informed consent to participate in the study.

Exclusion Criteria:

1. History of heart, liver, lung, kidney, digestive tract, blood system, neuropsychiatric system and other diseases, including anxiety and depression, that researchers deem clinically significant;
2. Comprehensive physical examination, neurological examination, laboratory examination, ECG examination, etc. indicate that the subject has abnormalities that are judged by the researcher as clinically significant;
3. Poor compliance with the pharmacodynamics training before administration;
4. Have taken any medication in the two weeks prior to study administration, and the investigator judges it may affect the evaluation results;
5. History of food and drug allergy or allergic reaction that the researcher determines to be clinically significant;
6. Serological examination (HBsAg, anti-HCV, anti-HIV, TP-Ab) with positive results;
7. History of alcohol or drug abuse within the year prior to study administration that the investigators believe may have affected the results assessed in this study;
8. Frequent (> 1 time per month) use of hypnotic drugs, and screening and baseline benzodiazepine urine screening positive;
9. Participants who need to work night shifts, stay up late, or stay at least 3 time zones away from the study site within 2 weeks before and during the study;
10. Subjects who could not maintain a regular sleep and rest schedule (get up at 6-8 am and go to sleep at 10-12 PM) within 1 week before and during the study and who were judged by the investigator to be likely to affect the results of this study;
11. Those who could not quit smoking and alcohol drinking as required during the study period or whose carbon monoxide breath test detected >7 ppm during the screening period (further confirmation by urine cotinine test if deemed necessary by the investigators);
12. Participants who have participated in any drug clinical trial as a subject within 3 months prior to study administration;
13. Patients who donated blood or blood products ≥400 mL or 2 units within three months prior to drug administration;
14. Those who do not agree to avoid the use of tobacco, alcohol or caffeinated beverages, or to avoid strenuous exercise, or to avoid other factors affecting the absorption, distribution, metabolism or excretion of drugs within 24 hours before and during the trial;
15. Don't agree or is unable to refrain from eating grapefruit or other related tropical fruits and beverages and from using St. John's Wort during the 24 hours prior to the first dose and during the study period;
16. Women who are pregnant or nursing, or who test positive for serum HCG before trial administration, or who cannot/do not use investigator-approved contraception during the study as required;
17. Those with abnormal cognitive function assessment (MMSE less than 26 points) and judged by the researchers to be clinically significant;
18. Subjects deemed unsuitable for this clinical study by the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Drug: Placebo	Drug: Placebo; Oral tablet
Experimental: Drug: YZJ-1139 high dose group; Subjects will be into two groups：Young adult subjects and elderly subjects	Drug: YZJ-1139; YZJ-1139
Experimental: Drug: YZJ-1139 low dose group; Subjects will be into two groups：Young adult subjects and elderly subjects	Drug: YZJ-1139; YZJ-1139
Active Comparator: Drug: Zolpidem	Drug: Zolpidem; Oral tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax of YZJ-1139、zolpidem	Cmax is defined as the maximum concentration of drug	From Day 1 to Day 2 post single dose；up to 4 weeks
AUCinf of YZJ-1139、zolpidem	AUCinf is defined as the concentration of drug extrapolated to infinite time	From Day 1 to Day 2 post single dose；up to 4 weeks
AUClast of YZJ-1139、zolpidem	AUClast is defined as the concentration of drug from time zero to the last observable concentration	From Day 1 to Day 2 post single dose；up to 4 weeks
Tmax of YZJ-1139、zolpidem	Tmax is defined as the time (observed time point) of Cmax	From Day 1 to Day 2 post single dose；up to 4 weeks
t1/2 of YZJ-1139、zolpidem		From Day 1 to Day 2 post single dose；up to 4 weeks
CL/F of YZJ-1139、zolpidem	CL/F is defined as the apparent oral clearance following administration of the drug	From Day 1 to Day 2 post single dose；up to 4 weeks
Vz/F of YZJ-1139、zolpidem	Vz/F is defined as the apparent volume of distribution of the drug	From Day 1 to Day 2 post single dose；up to 4 weeks
Left and right saccade peak velocity (SPV) of Eye Movements	Instruct the subject to fix their gaze on the red light spot on the LED display and move their eyes with the light spot. During the test, the head and body must remain still. The test consists of the following two parts, each lasting 2 minutes. Between the two parts, the subject should rest for a certain period of time based on their level of fatigue. Part 1: Scanning eye movements Part 2: Smooth pursuit eye movements.	From Day 1 to Day 2 post single dose；up to 4 weeks
left and right saccade accuracy rate (SacAcc) of Eye Movements	Instruct the subject to fix their gaze on the red light spot on the LED display and move their eyes with the light spot. During the test, the head and body must remain still. The test consists of the following two parts, each lasting 2 minutes. Between the two parts, the subject should rest for a certain period of time based on their level of fatigue. Part 1: Scanning eye movements Part 2: Smooth pursuit eye movements.	From Day 1 to Day 2 post single dose；up to 4 weeks
Left and right saccade eye movement response time (SacRT) of Eye Movements	Instruct the subject to fix their gaze on the red light spot on the LED display and move their eyes with the light spot. During the test, the head and body must remain still. The test consists of the following two parts, each lasting 2 minutes. Between the two parts, the subject should rest for a certain period of time based on their level of fatigue. Part 1: Scanning eye movements Part 2: Smooth pursuit eye movements.	From Day 1 to Day 2 post single dose；up to 4 weeks
Smooth eye movement to the left and right (Smooth) of Eye Movements	Instruct the subject to fix their gaze on the red light spot on the LED display and move their eyes with the light spot. During the test, the head and body must remain still. The test consists of the following two parts, each lasting 2 minutes. Between the two parts, the subject should rest for a certain period of time based on their level of fatigue. Part 1: Scanning eye movements Part 2: Smooth pursuit eye movements.	From Day 1 to Day 2 post single dose；up to 4 weeks
Body Sway	The subject takes off their shoes, spreads their feet shoulder-width apart, and stands on a flat ground 120 cm away from the measuring device. They close their eyes and stand for 2 minutes, and the test measures the body sway amplitude (mm) of the subject during the 2-minute closed-eye period. The test evaluates the subject's postural balance	From Day 1 to Day 2 post single dose；up to 4 weeks
Simple response time of Choice Reaction Time Test	The test lasts for 1 minute. During the test, there is a vertical line in the center of the screen. On both sides of the screen, random "left" or "right" words will appear. The participants are required to ignore the word meanings and click the "right" or "left" key based on the word's position.	From Day 1 to Day 2 post single dose；up to 4 weeks
Simple response accuracy rate of Choice Reaction Time Test	The test lasts for 1 minute. During the test, there is a vertical line in the center of the screen. On both sides of the screen, random "left" or "right" words will appear. The participants are required to ignore the word meanings and click the "right" or "left" key based on the word's position.	From Day 1 to Day 2 post single dose；up to 4 weeks
Selective response time of Choice Reaction Time Test	During the test, there was a dividing line in the middle of the screen. During the test, the word "left" or "right" appeared randomly on both sides of the screen. Subjects were asked to ignore the position of the word and click the key "right" or "left" according to the meaning of the word.	From Day 1 to Day 2 post single dose；up to 4 weeks
Selective response accuracy rate of Choice Reaction Time Test	During the test, there was a dividing line in the middle of the screen. During the test, the word "left" or "right" appeared randomly on both sides of the screen. Subjects were asked to ignore the position of the word and click the key "right" or "left" according to the meaning of the word.	From Day 1 to Day 2 post single dose；up to 4 weeks
The average reaction time for correct responses of Digit Symbol Substitution Test	The test time is not more than 2 minutes, the symbol is displayed on the screen, and the subject clicks the corresponding number according to the corresponding relationship between the symbol and the number given below. After clicking or exceeding the upper limit of the reaction time, the subject automatically enters the next symbol.	From Day 1 to Day 2 post single dose；up to 4 weeks
The number of correct responses of Digit Symbol Substitution Test	The test time is not more than 2 minutes, the symbol is displayed on the screen, and the subject clicks the corresponding number according to the corresponding relationship between the symbol and the number given below. After clicking or exceeding the upper limit of the reaction time, the subject automatically enters the next symbol.	From Day 1 to Day 2 post single dose；up to 4 weeks
The average reaction time for incorrect responses of Digit Symbol Substitution Test	The test time is not more than 2 minutes, the symbol is displayed on the screen, and the subject clicks the corresponding number according to the corresponding relationship between the symbol and the number given below. After clicking or exceeding the upper limit of the reaction time, the subject automatically enters the next symbol.	From Day 1 to Day 2 post single dose；up to 4 weeks
The number of incorrect responses of Digit Symbol Substitution Test	The test time is not more than 2 minutes, the symbol is displayed on the screen, and the subject clicks the corresponding number according to the corresponding relationship between the symbol and the number given below. After clicking or exceeding the upper limit of the reaction time, the subject automatically enters the next symbol.	From Day 1 to Day 2 post single dose；up to 4 weeks
The number of non-responses of Digit Symbol Substitution Test	The test time is not more than 2 minutes, the symbol is displayed on the screen, and the subject clicks the corresponding number according to the corresponding relationship between the symbol and the number given below. After clicking or exceeding the upper limit of the reaction time, the subject automatically enters the next symbol.	From Day 1 to Day 2 post single dose；up to 4 weeks
Immediate recall of Word Recall Test	About 1-2 hours after dosing， First, the subjects were shown 20 unrelated words, each word for a few seconds, and then the subjects were asked to immediately recall the words they just saw. The number of correct words in instantaneous recall was recorded respectively	From Day 1 to Day 2 post single dose；up to 4 weeks
Delayed recall of Word Recall Test	About 1-2 hours later, the subjects were allowed to freely recall the words again, which was delayed recall; The number of correct words in delayed recall was recorded respectively	From Day 1 to Day 2 post single dose；up to 4 weeks
Delayed recognition of Word Recall Test	The subjects were then presented with 40 words (of which 20 were previously presented words and 20 were confounding words), and were asked to answer one by one whether they were the words they had just seen. The number of correct words in delayed extraction was recorded respectively	From Day 1 to Day 2 post single dose；up to 4 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Adverse events (AEs)	From Day 1 to Day 2 post single dose；up to 4 weeks

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): March 7, 2019
• Primary Completion (Actual): April 10, 2019
• Study Completion (Actual): November 15, 2019

Study Registration Dates

• First Submitted: November 7, 2024
• First Submitted That Met QC Criteria: November 11, 2024
• First Posted (Estimated): November 12, 2024

Study Record Updates

• Last Update Posted (Estimated): November 12, 2024
• Last Update Submitted That Met QC Criteria: November 11, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Sleep Aids, Pharmaceutical; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Neurotransmitter Agents; Hypnotics and Sedatives; GABA Agents; GABA-A Receptor Agonists; GABA Agonists; Zolpidem
• Other Study ID Numbers: YZJ-1139-1-02

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No