Hepatic ImpairmentPhase 1NCT04145596
Safety and Pharmacokinetics/Pharmacodynamics of HSK3486 in Patients With Hepatic Impairment
A Phase 1 study testing HSK3486 in people with Hepatic Impairment, run by Sichuan Haisco Pharmaceutical Group Co., Ltd at 1 site in China.
Trial summary
Comparison of the pharmacokinetics/Pharmacodynamics of the HSK3486 in Patients With Mild and Moderate Hepatic Impairment Compared with Healthy Volunteers Read more about this study
- Who is it for?
- Ages 18 to 64 yearsHealthy volunteers can take part
- Conditions the study is for
- Hepatic Impairment
- What is being tested?
- HSK3486
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteChina
- Study dates
- 14 Nov 2019to 13 Jul 2020
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 64 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Sign the informed consent form and fully understand the content, procedure and possible adverse effects before the trial starts；
- Able to complete the study in compliance with the requirements of the clinical trial protocol;
- Subjects (including their partners) are willing to voluntarily adopt an effective measure of contraception starting from screening to 6 months after the last dose of the investigational drug.
- Male or female subjects aged 18-64 years old (including 18 and 64 years old);
- Male subjects weighing ≥ 50 kg, female subjects weighing ≥ 45 kg;Body mass index (BMI) = weight (kg)/height2 (m2); BMI of ≥ 18 and ≤ 30 kg/m2 (inclusive);
- Blood pressure between 90-149/60-94 mmHg (inclusive); heart rate between 55-100 bpm (inclusive); body temperature between 35.9-37.6°C (inclusive); respiratory rate between 12-20 breaths per min (inclusive); SpO2 when inhaling ≥ 95%;
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- Normal physical examination results or abnormal physical examination results with no clinical significance;
- For subjects with normal liver functions, their clinical laboratory tests (blood routine, blood biochemistry, urine routine, and coagulation function) should be normal or abnormal without clinical significance;
- No potential difficult airway (modified Mallampati score of Grade I to II);
- For subjects with normal liver functions, they should have no history of primary diseases in major organs, including but not limited to gastrointestinal, respiratory, renal, hepatic, neurological, hematological, , endocrine, oncological, immunological, psychiatric or cardiovascular and cerebrovascular diseases;
- Patients with Hepatic Insufficiency Must Also Meet the Following Inclusion Criteria:
- Child-Pugh grade A or B hepatic insufficiency caused by previous primary liver diseases: including non-alcoholic steatohepatitis and viral hepatitis (hepatitis B, hepatitis C);
- The liver function is determined by the investigators as stable within 14 days before drug administration;
- Have not used any drug or dosing regimen within 4 weeks before screening that can stabilize the primary liver disease.
Who cannot join
- Have not used any drug or dosing regimen within 4 weeks before screening that can stabilize the primary liver disease;
- Patient having contraindications to deep sedation/general anesthesia or a history of past sedation/anesthesia accidents;
- Known sensitivity to excipients in HSK3486 injectable emulsion (soybean oil, glycerin, triglyceride, egg lecithin, sodium oleate and sodium hydroxide); or with allergic constitution (including history of drug allergies and allergic diseases);
- History of alcohol abuse (> 2 units of alcohol consumed per day: 1 unit = 285 mL of beer, or 25 mL of liquor, or 100 mL of wine) within 3 months prior to screening;
- History of drug abuse within 3 months prior to screening, or a history of long-term use of benzodiazepines;
- Blood/plasma donation or blood loss of ≥ 200 mL, or plasma exchange within 30 days prior to screening;
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- In receipt of prescription drugs, Chinese herbal medicines, over-the-counter drugs or food supplements (such as vitamins and calcium supplements) other than contraceptives, paracetamol, non-steroidal anti-inflammatory drugs, topical over-the-counter preparations, within 2 weeks prior to screening (patients with hepatic insufficiency can also use drugs for treating primary liver diseases);
- Participated in other drug/medical device trials within 3 month prior to screening;
- Patients with clinically significant abnormalities in ECG (such as tachycardia/bradycardia requiring medication, II-III degree atrioventricular block or QTcF interval ≥ 450 ms (Fridericia's correction formula), or other clinically significant abnormalities determined by the clinician);
- Female subjects in lactation or having positive serum pregnancy test results during the screening period or the trial;
- Positive screening result of any indicators of hepatitis B surface antigen, hepatitis C antibody or hepatitis C core antigen, HIV antibody, or syphilis antibody (hepatitis B surface antigen, hepatitis C antibody or hepatitis C core antigen may be positive for patients with hepatic insufficiency);
- Subjects with serious or clinically significant infections (such as infections of the respiratory tract or central nervous system), trauma, or major surgery within 4 weeks prior to screening;
- Subjects expected to have surgery or hospitalization during the trial;
- Subjects who have consumed any beverages or foods containing alcohol (or positive alcohol breath test results), grapefruit juice or methylxanthine (such as coffee, tea, cola, chocolate, and functional drinks), participated in strenuous physical activities, and with other factors that may affect drug absorption, distribution, metabolism, and excretion within 1 day prior to dose administration;
- Subjects with positive urine drug screening results (morphine, methamphetamine, ketamine, marijuana, ecstasy pills);
- Subjects unsuitable for arterial blood collection, such as subjects who have positive Allen's test results;
- Subjects who are unable to fast for 8 hrs before dose administration;
- Subjects who have used propofol, other sedatives/anesthetics, and/or opioid analgesics or compounds containing analgesics within 72 hrs prior to dose administration;
- Subjects judged by the investigator to be unsuitable for participating in this trial for any reason.
- The Following Exclusion Criteria are Added for Patients with Hepatic Insufficiency:
- Clinical laboratory abnormalities with clinical significance, or other clinical findings showing the following illnesses with clinically significance, including but not limited to gastrointestinal, respiratory, renal, neural, hematological, endocrine, neoplastic, immunological, psychiatric or cardiovascular and cerebrovascular diseases other than primary liver diseases;
- Patients with liver failure, or with cirrhotic combined with hepatic encephalopathy, hepatocellular carcinoma, and esophageal and gastric variceal bleeding and other complications considered by the investigator as unsuitable for the clinical study;
- History of liver transplantation.
Trial locations and contacts
1 site in 1 country.
China1 site
Phase I Clinical Trial Laboratory, The First Hospital of Jilin University
Changchun, Jilin, 130021
About this study
Official title: A Phase 1 Study to Investigate a Single Bolus Dose Followed With a 30 Minute Constant Infusion of HSK3486 on the Safety and Pharmacokinetics/Pharmacodynamics of HSK3486 in Patients With Hepatic Impairment (Single-Center, Open-label, Parallel-Group)
Comparison of the pharmacokinetics/Pharmacodynamics of the HSK3486 in Patients With Mild and Moderate Hepatic Impairment Compared with Healthy Volunteers
Read the detailed description
This is a single-center, open-label, non-randomized, parallel-controlled Phase I clinical study carried out in patients with compensated chronic liver disease (Child-Pugh A), patients with decompensated chronic liver disease (Child-Pugh B), and age-, weight-, and gender-matched subjects with normal liver functions.
- Conditions
- Hepatic Impairment
- Being tested
- HSK3486
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HSK3486Drug
HSK3486，Initially 0.4 mg/kg was administered as a 1 minute bolus, followed immediately by a constant infusion dose of 0.4 mg/kg/h administered as a 30 minute infusion via infusion pump.
| Study group | Role | What they receive |
|---|---|---|
| Compensated Chronic Liver Disease (Child-Pugh A) | Active comparator | Not described Receives: Drug: HSK3486 |
| Decompensated Chronic Liver Disease (Child-Pugh B) | Active comparator | Not described Receives: Drug: HSK3486 |
| healthy volunteers（Normal liver functions） | Active comparator | Not described Receives: Drug: HSK3486 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Peak concentration (Cmax)
Cmax（a measure of the body's exposure to HSK3486）will be compared between normal hepatic function patients and Patients with Compensated Chronic Liver Disease (Child-Pugh A) or Patients with Decompensated Chronic Liver Disease (Child-Pugh B).
Measured: -30 minutes before administration until 24 hours post administration on day 1
Area under the concentration-time curve (AUC)
AUC（a measure of the body's exposure to HSK3486）will be compared between normal hepatic function patients and Patients with Compensated Chronic Liver Disease (Child-Pugh A) or Patients with Decompensated Chronic Liver Disease (Child-Pugh B).
Measured: -30 minutes before administration until 24 hours post administration on day 1
Secondary outcomes (6)
MOAA/S(modified observer's assessment of alert /sedation)
Measured: -5 minutes before administration until 1 hours post administration on day 1
Bispectral index(BIS)
Measured: -5 minutes before administration until 1 hours post administration on day 1
Tmax
time to peak observed
Measured: -30 minutes before administration until 24 hours post administration on day 1
Total clearance
Measured: -30 minutes before administration until 24 hours post administration on day 1
Volume of distribution
Measured: -30 minutes before administration until 24 hours post administration on day 1
blood pressure（systolic, diastolic and mean arterial pressure）
safety endpoits
Measured: from the screening to 3 days post-dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Oct 2019
- Study start14 Nov 2019
- Primary completion20 Apr 2020
- Study completion13 Jul 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Hepatic ImpairmentStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sichuan Haisco Pharmaceutical Group Co., Ltd
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- The First Hospital of Jilin University
- Responsible party
- Sponsor
- Investigators
- Yan-hua Ding, PhD, Study director, Phase I Clinical Trial Laboratory，The First Hospital of Jilin University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04145596
- Sponsor's protocol ID
- HSK3486-105
- Status last verified
- Dec 2020
- First submitted
- 23 Oct 2019
- Last updated
- 17 Dec 2020
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Qin L, Ren L, Wan S, Liu G, Luo X, Liu Z, Li F, Yu Y, Liu J, Wei Y. Design, Synthesis, and Evaluation of Novel 2,6-Disubstituted Phenol Derivatives as General Anesthetics. J Med Chem. 2017 May 11;60(9):3606-3617. doi: 10.1021/acs.jmedchem.7b00254. Epub 2017 Apr 28.
PubMed 28430430Hu Y, Li X, Liu J, Chen H, Zheng W, Zhang H, Wu M, Li C, Zhu X, Lou J, Yan P, Wu N, Liu X, Ma S, Wang X, Ding Y, Xuan C. Safety, pharmacokinetics and pharmacodynamics of a novel gamma-aminobutyric acid (GABA) receptor potentiator, HSK3486, in Chinese patients with hepatic impairment. Ann Med. 2022 Dec;54(1):2769-2780. doi: 10.1080/07853890.2022.2129433.
PubMed 36217101
Study at a glance
From the registry record, last updated by the sponsor on 17 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Study to Investigate a Single Bolus Dose Followed With a 30 Minute Constant Infusion of HSK3486 on the Safety and Pharmacokinetics/Pharmacodynamics of HSK3486 in Patients With Hepatic Impairment (Single-Center, Open-label, Parallel-Group)
- ClinicalTrials.gov ID
- NCT04145596
- Acronym / sponsor ID
- HSK3486-105
- Conditions
- Hepatic Impairment
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Sichuan Haisco Pharmaceutical Group Co., LtdIndustry (pharma, biotech, devices)
- Collaborators
- The First Hospital of Jilin University
- Study start
- 14 Nov 2019 (actual)
- Primary completion
- 20 Apr 2020 (actual)
- Study completion
- 13 Jul 2020 (actual)
- First posted
- 30 Oct 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Comparison of the pharmacokinetics/Pharmacodynamics of the HSK3486 in Patients With Mild and Moderate Hepatic Impairment Compared with Healthy Volunteers
Detailed description
This is a single-center, open-label, non-randomized, parallel-controlled Phase I clinical study carried out in patients with compensated chronic liver disease (Child-Pugh A), patients with decompensated chronic liver disease (Child-Pugh B), and age-, weight-, and gender-matched subjects with normal liver functions.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Compensated Chronic Liver Disease (Child-Pugh A) | Active comparator | Drug: HSK3486 |
| Decompensated Chronic Liver Disease (Child-Pugh B) | Active comparator | Drug: HSK3486 |
| healthy volunteers（Normal liver functions） | Active comparator | Drug: HSK3486 |
Who may qualify
- Ages
- 18 to 64 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (14 listed)
- Sign the informed consent form and fully understand the content, procedure and possible adverse effects before the trial starts；
- Able to complete the study in compliance with the requirements of the clinical trial protocol;
- Subjects (including their partners) are willing to voluntarily adopt an effective measure of contraception starting from screening to 6 months after the last dose of the investigational drug.
- Male or female subjects aged 18-64 years old (including 18 and 64 years old);
- Male subjects weighing ≥ 50 kg, female subjects weighing ≥ 45 kg;Body mass index (BMI) = weight (kg)/height2 (m2); BMI of ≥ 18 and ≤ 30 kg/m2 (inclusive);
Key exclusion criteria (23 listed)
- Have not used any drug or dosing regimen within 4 weeks before screening that can stabilize the primary liver disease;
- Patient having contraindications to deep sedation/general anesthesia or a history of past sedation/anesthesia accidents;
- Known sensitivity to excipients in HSK3486 injectable emulsion (soybean oil, glycerin, triglyceride, egg lecithin, sodium oleate and sodium hydroxide); or with allergic constitution (including history of drug allergies and allergic diseases);
- History of alcohol abuse (> 2 units of alcohol consumed per day: 1 unit = 285 mL of beer, or 25 mL of liquor, or 100 mL of wine) within 3 months prior to screening;
- History of drug abuse within 3 months prior to screening, or a history of long-term use of benzodiazepines;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HSK3486HSK3486，Initially 0.4 mg/kg was administered as a 1 minute bolus, followed immediately by a constant infusion dose of 0.4 mg/kg/h administered as a 30 minute infusion via infusion pump. | Drug | Compensated Chronic Liver Disease (Child-Pugh A), Decompensated Chronic Liver Disease (Child-Pugh B), healthy volunteers（Normal liver functions） |
Primary outcome
Peak concentration (Cmax)
Time frame: -30 minutes before administration until 24 hours post administration on day 1
Cmax（a measure of the body's exposure to HSK3486）will be compared between normal hepatic function patients and Patients with Compensated Chronic Liver Disease (Child-Pugh A) or Patients with Decompensated Chronic Liver Disease (Child-Pugh B).
Area under the concentration-time curve (AUC)
Time frame: -30 minutes before administration until 24 hours post administration on day 1
AUC（a measure of the body's exposure to HSK3486）will be compared between normal hepatic function patients and Patients with Compensated Chronic Liver Disease (Child-Pugh A) or Patients with Decompensated Chronic Liver Disease (Child-Pugh B).
6 secondary outcomes
MOAA/S(modified observer's assessment of alert /sedation)
Time frame: -5 minutes before administration until 1 hours post administration on day 1
Bispectral index(BIS)
Time frame: -5 minutes before administration until 1 hours post administration on day 1
Tmax
Time frame: -30 minutes before administration until 24 hours post administration on day 1
Total clearance
Time frame: -30 minutes before administration until 24 hours post administration on day 1
Volume of distribution
Time frame: -30 minutes before administration until 24 hours post administration on day 1
blood pressure（systolic, diastolic and mean arterial pressure）
Time frame: from the screening to 3 days post-dose
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Dec 2020.
- Results publication: PubMed 28430430Qin L, Ren L, Wan S, Liu G, Luo X, Liu Z, Li F, Yu Y, Liu J, Wei Y. Design, Synthesis, and Evaluation of Novel 2,6-Disubstituted Phenol Derivatives as General Anesthetics. J Med Chem. 2017 May 11;60(9):3606-3617. doi: 10.1021/acs.jmedchem.7b00254. Epub 2017 Apr 28.
- Derived from this study: PubMed 36217101Hu Y, Li X, Liu J, Chen H, Zheng W, Zhang H, Wu M, Li C, Zhu X, Lou J, Yan P, Wu N, Liu X, Ma S, Wang X, Ding Y, Xuan C. Safety, pharmacokinetics and pharmacodynamics of a novel gamma-aminobutyric acid (GABA) receptor potentiator, HSK3486, in Chinese patients with hepatic impairment. Ann Med. 2022 Dec;54(1):2769-2780. doi: 10.1080/07853890.2022.2129433.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Yan-hua Ding, PhD study director
Phase I Clinical Trial Laboratory，The First Hospital of Jilin University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing HSK3486 in people with Hepatic Impairment, run by Sichuan Haisco Pharmaceutical Group Co., Ltd at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Peak concentration (Cmax) (time frame: -30 minutes before administration until 24 hours post administration on day 1). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04145596, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Dec 2020.