A Study Evaluating Safety, Tolerability, and Pharmacokinetics/Pharmacodynamics of Single IV Dose of HSK3486 Injectable Emulsion in Healthy Subjects.

A Single-center, Open-label, Uncontrolled, and Dose-escalation Study Evaluating Safety, Tolerability, and Pharmacokinetics/Pharmacodynamics of Single IV Dose of HSK3486 Injectable Emulsion in Healthy Subjects.

his single-center, open-label, uncontrolled, and dose-escalation study evaluated the safety, tolerability, and pharmacokinetics/pharmacodynamics of single IV dose of HSK3486 injectable emulsion in healthy subjects.

Study Overview

• Status: Completed
• Conditions: Anesthesia; Sedation
• Intervention / Treatment: Drug: HSK3486

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 49 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Healthy males or females with full capacity for civil conduct, between 18 and 49 years old (inclusive);
2. Body weight > 45 kg, and body mass index (BMI) ≥ 19 and ≤24 kg/m2;
3. Blood pressure between 90-140/60-90 mmHg; heart rate between 60-99 bpm; body temperature between 35.8-37.5 ºC; respiration rate between 12-24 breaths per minute; SpO2 when inhaling > 95%;
4. Normal physical examination, laboratory tests (blood routine, blood biochemistry, and urine routine), 12-Led ECG, posteroanterior and lateral chest x-ray, and or abnormal but without clinical significance (determined by investigator); no potential difficult airway;
5. Subjects must understand the procedures and methods of this study, and be willing to provide informed consent and to complete the trial in strict accordance with clinical trial protocol.

Exclusion Criteria:

1. Known sensitivity to propofol, excipient in propofol medium and long chain fat emulsion injection, excipient in HSK3486 injectable emulsion;
2. contraindicated in general anesthesia;

3. Received any one of the following medications or treatments prior to screening/enrollment:

   1. History of medication abuse or any signs of chronic benzodiazepines use (such as insomnia, anxiety, spasms) within 3 months prior to screening, or a positive urine medication test (during screening or at baseline);
   2. Participated in clinical trials involving any medications or medical devices within 3 months prior to screening, or participated in 3 or more drug clinical trials within the past year;
4. History or evidence of increased risk of sedation or anesthesia, such as cardiovascular disease, respiratory disease, cerebrovascular disease, gastrodintestinal disease and other system disease prior to the screening and/or baseline period;

5. Laboratory results that meet any of the following during screening/enrollment:

   1. Positive for HBsAg, HCV, or HIV;

   2. Abnormal hepatic or renal function confirmed after re-examination;

      • ALT or AST > ULN;
      • Creatinine > ULN;
6. History of smoking for more than 3 weeks and/or respiratory irritation caused by smoking within 3 months prior to screening;
7. History of alcohol abuse within 3 months prior to screening or a positive alcohol test (baseline);
8. Women who are pregnant or breastfeeding; women of child-bearing potential or men who are unwilling to use contraception during the trial;
9. Subjects judged by the investigator to be unsuitable for participating in this trial for any reason.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HSK3486; 0.15mg/kg, 0.40mg/kg, 0.60mg/kg, 0.90mg/kg,	Drug: HSK3486; Mmanual IV bolus injection completed in 1 minute.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety by measurement of Adverse Events		First dose of study drug on day 1
Apnea	No movement of chest wall and cessation of end-tidal carbon dioxide waveform > 15 seconds.	First dose of study drug on day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Median effective dose (ED50)		From first dose of study drug until fully alert on day 1
Peak concentration (Cmax)		From the start of administration to 48 hours after administration
Time to plasma peak concentration(Tmax)		From the start of administration to 48 hours after administration
Terminal elimination half life (t1/2z) and mean residence time (MRT)		From the start of administration to 48 hours after administration
Mean residence time (MRT)		From the start of administration to 48 hours after administration
Area Under the Curve (AUC0-30min, AUC0-1h, AUC0-last, and AUC0-inf)		From the start of administration to 48 hours after administration
Total clearance (CL)		From the start of administration to 48 hours after administration
Modified observer's assessment of alertness/sedation（MOAA/S）	Observe the change of modified observer's assessment of alert /sedation during the whole trial	From first dose of study drug until fully alert on day 1
Bispectral index （BIS）		From first dose of study drug until fully alert on day 1

Collaborators and Investigators

• Sponsor: Sichuan Haisco Pharmaceutical Group Co., Ltd

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2016
• Primary Completion (Actual): August 1, 2016
• Study Completion (Actual): August 1, 2016

Study Registration Dates

• First Submitted: December 6, 2018
• First Submitted That Met QC Criteria: December 10, 2018
• First Posted (Actual): December 12, 2018

Study Record Updates

• Last Update Posted (Actual): March 3, 2020
• Last Update Submitted That Met QC Criteria: March 1, 2020
• Last Verified: August 1, 2016

More Information

Terms related to this study

• Other Study ID Numbers: HSK3486-101

Drug and device information, study documents

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