A Phase IIa Study Investigating the Tolerance, Efficacy and Safety of HSK3486

A Phase IIa, Open-label, Propofol-controlled ,Dose-escalation, Multi-center Study to Evaluate the Tolerance, Efficacy and Safety of HSK3486 for Induction of General Anesthesia in Elective Surgery Patients.

This is a Phase IIa, open-label, propofol-controlled ,dose-escalation, multi-center Study to evaluate the tolerance, efficacy and safety of HSK3486 for induction of general anesthesia in elective surgery patients.This study is consisted of two cohorts, dose-escalation and dose-expansion cohorts. The doses in dose- expansion cohort were selected from dose-escalation results.

Study Overview

• Status: Completed
• Conditions: Induction of General Anaesthesia
• Intervention / Treatment: Drug: HSK3486; Drug: Propofol

• Study Type: Interventional
• Enrollment (Actual): 114
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Zhejiang
    • Wenzhou, Zhejiang, China, 325027
      • The 2nd Affiliated Hospital of WMU

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Inpatients required tracheal intubation under general anesthesia and a non-emergency non-cardiothoracic and non-extracranial elective surgery for an estimated duration of ≤ 3 h ;.
2. Males or females, aged ≥ 18 and ≤ 65 years old;
3. Body mass index (BMI) ≥ 19 and ≤ 30 kg/m2;
4. ASA grade I~II;
5. Capable of understanding the procedure and method of this study, willing to sign an informed consent form and to complete this study in strict accordance with the study protocol.

Exclusion Criteria:

1. Patients were contraindicated in general anesthesia.;
2. Patients with a known sensitivity to propofol, opioids, naloxone, eggs, soy products or a medical condition such that these agents were contraindicated
3. Patients in receipt of any investigational drug within 30 days before screening.
4. Patients in receipt of propofol, opioid , other sedative or anesthetic or analgesics within one month prior to the screening period.
5. Patients in receipt of general anesthesia surgery within two weeks prior to the screening period.
6. The patient has some history or evidence of increased risk of sedation or anesthesia, such as cardiovascular disease, respiratory disease, cerebrovascular disease, liver, kidney, blood system, or metabolic system disease prior to the screening period.
7. Abnormal laboratory results consisting of any of the following: :

1) AST and ALT≥ 2×ULN； 2）TBIL≥ 1.5×ULN； 3）Hb≤ 90g/L; 4）ANC≤1.5×109/L; 5) PLT≤80×109/L； 6） serum creatinine≥ 1.5×ULN.

8. Patients with a history of drug or ethanol abuse with the past 3 months. 9. Pregnant women or female patients with a positive serum or urine human chorionic gonadotropin pregnancy test at screening or baseline or lactating female patients. . 10. 10. Patients with a positive Allen 's test who collected arterial blood for PK study.

11. Patients with respiratory management difficulties. 12. Patients with an inability to communicate well with the investigator, or deemed unsuitable according to the investigator (in each case providing a reason).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HSK3486; Dose Escalation Cohort: 0.1 mg/kg, 0.2 mg/kg, 0.3mg/kg 0.4 mg/kg 0.5 mg/kg, 0.6 mg/kg, 0.7mg/kg, 0.8 mg/kg Dose Expansion Cohort: 0.3 mg/kg and 0.5 mg/kg.	Drug: HSK3486; For induction of general anesthesia In dose escalation cohort: Starting from 0.4mg/kg, up-titration dose by 0.1mg/kg until 0.8mg//kg or down-titration dose by 0.1mg/kg until 0.1mg/kg based on the efficacy and safety results.
Active Comparator: Propofol; Dose Escalation Cohorts:2.0mg/kg and 2.5mg/kg; Dose Expansion Cohorts: 2.0mg/kg	Drug: Propofol; For induction of general anesthesia

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The success rate of induction of general anesthesia	To find the MTD or the RP2D of HSK3486 in the induction of general anesthesia, the success rate of induction of general anesthesia is the primary outcome measurement.	during induction of general anesthesia on day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time from start of IMP administration to loss of eyelash reflex		during induction of general anesthesia on day 1
Time from start of IMP administration to loss of consciousness		during induction of general anesthesia on day 1
Time from start of IMP administration to intubation and the intubation reaction		during induction of general anesthesia on day 1
Mini-Mental State Examination (MMSE) total scores(0-30) by time point	Change from baseline in Mini-Mental State Examination (MMSE) total score	Pre-dose to 48 hours post-dose
change from baseline in blood pressure （systolic, diastolic and mean arterial pressure)	safety endpoits	pre-dose to 20 minutes post-dose
change from baseline in heart rate	safety endpoits	pre-dose to 20 minutes post-dose
change from baseline in arterial oxygen saturation	safety endpoits	pre-dose to 20 minutes post-dose
Number of patients with adverse events	safety endpoits	Pre-dose to 48 hours post-dose

Collaborators and Investigators

• Sponsor: Sichuan Haisco Pharmaceutical Group Co., Ltd

Study record dates

Study Major Dates

• Study Start (Actual): December 6, 2016
• Primary Completion (Actual): June 29, 2018
• Study Completion (Actual): July 18, 2018

Study Registration Dates

• First Submitted: September 18, 2018
• First Submitted That Met QC Criteria: October 5, 2018
• First Posted (Actual): October 9, 2018

Study Record Updates

• Last Update Posted (Actual): October 9, 2018
• Last Update Submitted That Met QC Criteria: October 5, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Central Nervous System Depressants; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Hypnotics and Sedatives; Propofol
• Other Study ID Numbers: HSK3486-202

Drug and device information, study documents

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