A Phase I Clinical Study Evaluating the Safety, Tolerability and Pharmacokinetics of HSK21542 in Healthy Volunteers
Avance Clinical
72 participants
Dec 4, 2019
Interventional
Conditions
Summary
The research project is testing a potential new treatment for acute and chronic pain called HSK21542. Before a new medicine can be approved for use for humans, it is necessary to confirm that it is safe and effective. This is done by carrying out clinical research studies such as this one. The purpose of this study is to evaluate the safety and tolerability of a single dose of HSK21542. The pharmacokinetics (PK) of HSK21542 in humans will also be determined. PK testing involves taking blood, urine and faeces to measure how much of the drug get into the bloodstream and how long the body takes to get rid of it. When testing for PK the sample will also be tested for metabolites (breakdown products)of HSK21542.
Eligibility
Inclusion Criteria11
- Healthy Volunteers:
- Males and females aged 18–45 years old (inclusive) at screening;
- Male volunteers no less than 50 kg, or female volunteers no less than 45 kg, with body mass index [BMI] in the range of 18.0–30.0 kg/m2 (inclusive) at screening;
- Healthy volunteers, as assessed by the investigator based on past medical history, comprehensive physical examination, vital signs, and specified tests and examinations.
- Female volunteers must:
- a. Be of nonchildbearing potential ie, surgically sterilized (hysterectomy, bilateral salpingectomy, bilateral oophorectomy at least 6 weeks before screening) or postmenopausal (where postmenopausal is defined as no menses for 12 months without an alternative medical cause), or
- b. If of childbearing potential, must have a negative pregnancy test at screening (serum test) and before study drug administration (Day -1 urine test). They must agree not to attempt to become pregnant, must not donate ova, and must use a highly effective contraceptive method from signing the consent form until at least 90 days after the last dose of study drug.
- .Be non-smokers (including tobacco and e-cigarettes) for at least 1 month prior to participation in the study.
- Male volunteers, if not surgically sterilized, must be willing not to donate sperm and, if engaging in sexual intercourse with a female partner who could become pregnant, must be willing to use a condom in addition to having the female partner use a highly effective contraceptive method from signing the consent form until at least 90 days after the last dose of study drug.
- Fully understand the nature, purpose, and potential benefits, inconveniences and risks of the trial. Understand the study procedure and voluntarily provide written informed consent.
- 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 Criteria17
- Any previous serious clinical conditions of the circulatory system, endocrine system, nervous system, digestive system, respiratory system, and hematological, immunological, psychiatric and metabolic abnormalities, or any disease or physiological condition that may interfere with the results of this trial;
- Clinically significant abnormalities upon physical examination, vital signs monitoring, ECG, and laboratory tests (including hematology, urinalysis, biochemistry, coagulation, thyroid function), as assessed by the investigator at screening;
- Volunteers with positive hepatitis B surface antigen, positive hepatitis C antibody, positive Treponema pallidum antibody, or positive human immunodeficiency virus (HIV) antibody test results;
- QTcF > 450 msec upon ECG;
- Volunteers who have a history of a severe drug hypersensitivity/anaphylaxis or who are allergic to two or more drugs and foods or who are allergic to any of the ingredients in the study drug including its excipients;
- Volunteers who cannot tolerate venipuncture and/or have a history of hemophobia or fear of needles;
- History of long-term excessive intake (more than 8 cups per day, one cup = 250 mL) of tea, grapefruit, coffee, or caffeinated or grapefruit-based beverages;
- Volunteers with a history of alcohol abuse within 3 months prior to screening, that is, more than 14 units of alcohol per week (1 unit = 285 mL of full strength beer (4.8% alcohol), 375 mL of mid strength beer (3.5% alcohol), 425 mL of low strength beer (2.7% alcohol), 30 mL of 40% hard liquor, 100 mL of wine);
- Volunteers with a positive alcohol breath test;
- Volunteers with a positive urine nicotine test;
- Volunteers with drug abuse or dependence, or with a positive urine drugs of abuse test;
- Use of any prescription medications or over-the-counter medications (including herbal medicines, diet aids, vitamins, or hormone supplements) within 14 days or 5 half-lives of the medication (whichever is longer) prior to dose administration, except occasional use of paracetamol;
- Blood donation or loss of blood > 450 mL within the past 3 months;
- Participation in any clinical trials within the past 3 months;
- For females of childbearing potential, a positive serum pregnancy test at screening or a positive urine pregnancy test with confirmatory serum pregnancy test on Day -1;
- Volunteers who plan to become pregnant within the next 6 months;
- Any other factors judged by the investigator to be unsuitable for participating in this study.
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Interventions
This is a double-blinded, placebo controlled, single ascending dose (SAD), multi-cohort trial. concentrations, HSK21542 concentration, pharmacokinetics parameters and identification of HSK21542 metabolites in urine. Also faeces samples will be collected, and faecal weight recorded pre-dose and at specified time intervals up to 48 h post dose for determination of HSK21542 concentration and identification of HSK21542 metabolites in feces. The study will consist of a total of 72 participants are planned to be enrolled and allocated into 9 dose cohorts at the following dose levels: 0.2, 0.5, 1, 1.5 , 0.02, 0.05 and 1 µg/kg by intravenous injection at 40 mL/h over a period of 15 minutes using an intravenous pump. Each dose cohort will include 8 participants (active:placebo = 6:2). Each participant can only be involved in one dose cohort. Participants receiving HSK21542 will be given a single dose of HSK21542 via intravenous injection on Day 1, and participants receiving placebo will be given a single dose of matched placebo via intravenous injection on Day 1 with same administration as active drug. Participants will be confined at the clinical facility from Day -1 through to Day 3, when they will be discharged following completion of all assessments. Participants will return to the clinical facility for final safety assessments at an End of Study (EOS) visit on Day 8 ± 1 day. Dosing in each dose cohort will start with two sentinel participants with one of the two sentinels randomized to receive HSK21542 and the other randomized to receive placebo. The safety and tolerability of each sentinel will be monitored until Day 3 and will be reviewed prior to dosing the remainder of participants in each cohort. The study principal investigator (PI) will review safety/tolerability information available on the sentinel participants on Day 3 and will make the decision to dose the remaining 6 participants in the cohort. Cohorts will be dosed in an escalating order, each dose level increased by no more than 2.5-fold over the previous dose level. The dose of a cohort may be appropriately adjusted according to the results of the previous dose cohort. The decision to escalate between dose levels will be based upon review of blinded safety data (ie, haematology, biochemistry, coagulation, thyroid function, blood electrolytes, ECG, vital signs and AE data) through to Day 8 and available blinded PK data by the Safety Monitoring Group (SMG). The SMG will consist of the PI, an independent Medical Monitor and a sponsor medical representative. The SMG will review the data, discuss the findings, and decide to: a) enrol the next dose group at the protocol-defined higher dose level; b) enrol the next dose group at an intermediate higher dose level; c) enrol the next dose group at a lower dose level than the current dose level; or d) terminate enrollment in the study. If the dose level is determined not to be safe and tolerated, the study drug assignment for those participants with a safety concern may be unblinded. Dosing will proceed to the next dose level until evaluation of the maximum dose specified in the protocol (20 µg/kg) or the trial is stopped by the SMG. The trial can be terminated at any stage during escalation when any of the criteria for termination are met, even if the maximum dose is not reached. For Cohort 4 (1,5µg/kg dose) only: Urine samples will be collected pre-dose and at specified time intervals up to 48 h post dose for determination of electrolyte (sodium, potassium, calcium, magnesium, and chlorine) concentrations, HSK21542 concentration, pharmacokinetics parameters and identification of HSK21542 metabolites in urine. Also faeces samples will be collected, and faecal weight recorded pre-dose and at specified time intervals up to 48 h post dose for determination of HSK21542 concentration and identification of HSK21542 metabolites in feces.
Locations(1)
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ACTRN12619001739101