Clinical trial NCT04213196: Safety, Tolerability and Pharmacokinetics of HSK21542 in Healthy Volunteers
Official title: A Phase I Clinical Study Evaluating the Safety, Tolerability and Pharmacokinetics of HSK21542 in Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Lead sponsor: Haisco Pharmaceutical Group Co., Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Second Affiliated Hospital, School of Medicine, Zhejiang University
First posted: 2019-12-30
Enrollment: 66
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: This is a first-in-human, Phase I, single-dose escalation clinical trial conducted in Chinese healthy volunteers. The safety, tolerability, and PK of HSK21542 injection in healthy volunteers will be evaluated using a randomized, double-blind, placebo-controlled trial design


Eligibility criteria: Inclusion Criteria:

1. Males and females aged 18-45 years old (inclusive) at screening;
2. Male volunteers no less than 50 kg, or female volunteers no less than 45 kg, with body mass index \[BMI\] in the range of 18.0-27.0 kg/m2 (inclusive) at screening;
3. Healthy volunteers, as assessed by the investigator based on past medical history, comprehensive physical examination, vital signs, and specified tests and examinations.
4. Fully understand the nature, purpose, and potential benefits, inconveniences and risks of the trial. Understand the study procedure and voluntarily provide written informed consent.
5. Able to communicate with the investigator and to follow all requirements of the study, and willing to be admitted into the phase I clinical facility.

Exclusion Criteria:

1. Those who have suffered or are currently suffering from any clinical serious disease such as circulatory system, endocrine system, nervous system, digestive system, respiratory system, hematology, immunology, psychiatry and metabolic abnormality or any other disease or physiological condition that can interfere with the results;
2. Physical examination, vital sign monitoring, ECG examination, chest anteroposterior and lateral radiographs, laboratory examination (including blood routine, urine routine, blood biochemistry, coagulation function, thyroid function, blood pregnancy (only for female subjects) during screening period, and the researcher judged that the abnormality had clinical significance;
3. People with positive hepatitis B surface antigen, positive hepatitis C antibody, positive Treponema pallidum antibody, or positive AIDS virus antibody test;
4. Patients with QTcF\>450 ms in ECG examination during screening;
5. Allergic constitution: such as those who are allergic to two or more drugs and foods; Or those who are allergic to any ingredient in this product and auxiliary materials; (Auxiliary materials: glacial acetic acid, sodium acetate, water for injection)
6. Those who cannot tolerate venipuncture and/or have a history of blood and needle sickness;
7. Those who have drunk too much tea, grapefruit, coffee, caffeinated or grapefruit drinks for a long time (more than 8 cups a day, 1 cup=250mL);
8. Those who have a history of alcohol abuse within 3 months before screening, that is, those who drink more than 14 units of alcohol per week (1 unit=12 ounces or 360 mL of beer, 1.5 ounces or 45 mL of spirits with 40% alcohol content, 5 ounces or 150 mL of wine), or those who have positive alcohol breath test;
9. Volunteers with a positive urine nicotine test;
10. Volunteers with drug abuse or dependence, or with a positive urine drugs of abuse test;
11. Those who have used any prescription medicine, over-the-counter medicine, Chinese herbal medicine and health care products within 14 days
12. Blood donation or loss of blood \> 450 mL within the past 3 months;
13. Participation in any clinical trials within the past 3 months;
14. Volunteers who plan to become pregnant within the next 6 months;
15. Any other factors judged by the investigator to be unsuitable for participating in this study.

Primary outcomes:
measure: AE/serious AE
timeFrame: From screening up to 3 weeks
measure: Vital signs: Systolic and Diastolic Blood Pressure
timeFrame: From screening up to 3 weeks
measure: Ramsay sedation score
timeFrame: -60 minutes before administration until 24 hours after administration
measure: Visual analog scale (VAS) addiction score
timeFrame: from administration to 24 hours after administration
Secondary outcomes:
measure: Peak concentration (Cmax)
timeFrame: -30 minutes before administration until 24 hours after administration
measure: Area under the concentration-time curve（AUC）
timeFrame: -30 minutes before administration until 24 hours after administration
measure: Tmax
timeFrame: -30 minutes before administration until 24 hours after administration
measure: Total clearance
timeFrame: -30 minutes before administration until 24 hours after administration
measure: Prolactin level
timeFrame: before administration until 24 hours after administration
measure: Antidiuretic hormone level
timeFrame: before administration until 24 hours after administration
measure: Urine volume
timeFrame: before administration until 24 hours after administration
Other outcomes:
Locations:
city: Hangzhou
country: China
facility: Second Affiliated Hospital of Zhejiang University School of Medicine
Study officials:
affiliation: The Second Affiliated Hospital of Zhejiang University Medical College
name: Min Yan, PhD
role: STUDY_DIRECTOR
affiliation: The Second Affiliated Hospital of Zhejiang University Medical College
name: Hong-gang Lou, PhD
role: STUDY_DIRECTOR
References:
citation: Zollner C, Mousa SA, Fischer O, Rittner HL, Shaqura M, Brack A, Shakibaei M, Binder W, Urban F, Stein C, Schafer M. Chronic morphine use does not induce peripheral tolerance in a rat model of inflammatory pain. J Clin Invest. 2008 Mar;118(3):1065-73. doi: 10.1172/JCI25911.