Efficacy and Safety of HSK3486 Compared to Propofol in Induction of General Anesthesia in Adults Having Elective Surgery

• ClinicalTrials.gov Identifier: NCT04711837
• Recruitment Status: Completed
• First Posted: January 15, 2021
• Results First Posted: May 26, 2023
• Last Update Posted: October 6, 2023
• Sponsor: Haisco-USA Pharmaceuticals, Inc.
• Information provided by (Responsible Party): Haisco-USA Pharmaceuticals, Inc.

Tracking Information

• First Submitted Date: January 12, 2021
• First Posted Date: January 15, 2021
• Results First Submitted Date: March 28, 2023
• Results First Posted Date: May 26, 2023
• Last Update Posted Date: October 6, 2023
• Actual Study Start Date: February 11, 2021
• Actual Primary Completion Date: April 13, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 21, 2023)

Number of Participants With Successful Anesthesia Induction [ Time Frame: From start of drug administration to MOAA/S ≤1 (up to 5 minutes) ]

The primary outcome of interest was the success rate of anesthesia induction, defined by the proportion of subjects with successful anesthesia. A subject was considered successful for anesthetic induction if the following conditions were met: induction success Modified Observer's Assessment of Awareness/Sedation Scale (MOAA/S ≤1) after administration of study drug and 1 or less top-up dose required without using any rescue drugs. Where Grade 0 is no response after trapezius squeeze, Grade 1 responds only after painful trapezius squeeze and Grade 5 is completely awake responds to name spoken in normal tone.

• Original Primary Outcome Measures (submitted: January 13, 2021): Success rate of general anesthesia induction [ Time Frame: From start of drug administration to MOAA/S ≤1 (up to 5 minutes) ]

Current Secondary Outcome Measures (submitted: April 21, 2023)

• Subjects' NRS Pain Score [ Time Frame: Up to 5 minutes ]
  Injection-site pain is evaluated verbally during study drug administration using the Numeric Rating Scale (NRS), ranging from 0 (no pain) to 10 (worse imaginable pain). Subjects' NRS pain score at the time of study drug administration (Day 1) and recall of pain score in PACU.
• Proportion of Subjects With Successful Induction Who Maintain the Desired Depth of Anesthesia for General Elective Surgery, AND Without Significant Cardiac and Respiratory Depression. [ Time Frame: 15 minutes from end of drug administration. ]
  The proportion of subjects with successful induction who maintain the desired depth of anesthesia for general elective surgery, AND without significant cardiac and respiratory depression between the time of successful induction and 15 minutes post initiation of study drug administration, or up to the beginning of second tracheal intubation attempt if it is a difficult condition and not beyond 15 minutes post initiation of study drug administration.
• Proportion of Subjects With Any Injection-site Pain on Numeric Rating Scale. [ Time Frame: From start of drug administration to MOAA/S ≤1 (up to 5 minutes) ]
  The proportion of subjects with any injection-site pain at time of drug administration on the Numeric Rating Scale (NRS ≥1).
• Time to Successful Induction of General Anesthesia. [ Time Frame: From start of drug administration to MOAA/S ≤1 (up to 5 minutes) ]
  Time from the end of the first administration of the study drug to MOAA/S ≤1.

Original Secondary Outcome Measures (submitted: January 13, 2021)

• Proportion of subjects with successful induction who maintain the desired depth of anesthesia for general elective surgery, AND without significant cardiac and respiratory depression. [ Time Frame: 15 minutes from end of drug administration. ]
• Proportion of subjects with any injection-site pain on Numeric Rating Scale. [ Time Frame: From start of drug administration to MOAA/S ≤1 (up to 5 minutes) ]

Current Other Pre-specified Outcome Measures (submitted: April 21, 2023)

• Time to the Disappearance of Eyelash Reflex [ Time Frame: From start of drug administration to disappearance of eyelash reflex (up to 5 minutes) ]
  Time from the end of the first administration of the study drug to the disappearance of eyelash reflex.
• Number of Participants That Failed to Meet Successful Induction of General Anesthesia [ Time Frame: From start of drug administration to MOAA/S ≤1 (up to 5 minutes) ]
  Failed to meet successful induction of general anesthesia defined by the use of the Top-up Study Drug and Rescue/Remediation Drugs

Original Other Pre-specified Outcome Measures (submitted: January 13, 2021)

• Time to successful induction of general anesthesia. [ Time Frame: From start of drug administration to MOAA/S ≤1 (up to 5 minutes) ]
• Time to the disappearance of eyelash reflex [ Time Frame: From start of drug administration to disappearance of eyelash reflex (up to 5 minutes) ]
• Change of BIS during the period of anesthesia post study drug administration [ Time Frame: 15 minutes from end of drug administration. ]
• Use of the top-up study drug and rescue/remediation drugs. [ Time Frame: From start of drug administration to MOAA/S ≤1 (up to 5 minutes) ]

Descriptive Information

• Brief Title: Efficacy and Safety of HSK3486 Compared to Propofol in Induction of General Anesthesia in Adults Having Elective Surgery
• Official Title: A Multicenter, Randomized, Double-blinded, Propofol-controlled, Phase 3 Clinical Study to Evaluate the Efficacy and Safety of HSK3486 Injectable Emulsion for Induction of General Anesthesia in Adults Undergoing Elective Surgery.
• Brief Summary: This is a multicenter, randomized, double-blinded, propofol-controlled, Phase 3 clinical study to evaluate the efficacy and safety of HSK3486 for induction of general anesthesia in adults undergoing elective surgery.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Anesthesia

Intervention

• Drug: HSK3486
  HSK3486 for induction of general anesthesia.
• Drug: Propofol
  Propofol for induction of general anesthesia.
  Other Name: Diprivan

Study Arms

• Experimental: HSK3486
  HSK3486 for induction of general anesthesia.
  Intervention: Drug: HSK3486
• Active Comparator: Propofol
  Propofol for induction of general anesthesia.
  Intervention: Drug: Propofol

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 21, 2023): 255
• Original Estimated Enrollment (submitted: January 13, 2021): 351
• Actual Study Completion Date: April 20, 2022
• Actual Primary Completion Date: April 13, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Subjects undergoing elective surgery (nonemergency, noncardiothoracic, and nonintracranial surgery anticipated to last at least 1 hour ).
• Males or females, aged ≥18 years old, with American Society of Anesthesiologists Physical Status (ASA PS) I to IV.
• Body mass index (BMI) ≥18 kg/m2.
• For all females of childbearing potential, negative pregnancy test at screening and baseline. Additionally, females of childbearing potential must agree to use birth control (such as condom, intrauterine device [IUD], abstinence) from the time of consent until 30 days post study drug administration.
• Capable of understanding the procedures and methods of this study, willing to sign an Informed Consent Form, and to complete this study in strict compliance with the study protocol.

Exclusion Criteria:

• Contraindications to deep sedation/general anesthesia or a history of adverse reaction to sedation/general anesthesia.
• Known to be allergic to eggs, soy products, opioids and their antidotes, or propofol; subject having contraindications to propofol, opioids, and their antidotes.
• Medical condition or evidence of increased sedation/general anesthesia risk.
• Management risks of respiratory tract and judged by the investigator to be unsuitable for inclusion in the study.
• Any medication that has the potential to interact synergistically with propofol or HSK3486, including but not limited to all sedatives and hypnotics.
• Laboratory parameters significantly out of range at screening.
• Female subjects with a positive pregnancy test (serum or urine) at screening or baseline; lactating subjects; any subject planning to get pregnant within 1 month after the study (including the male subject's partner).
• Judged by the investigator to have any other factors that make the subject unsuitable for participation in the study.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04711837
• Other Study ID Numbers: HSK3486-304
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Haisco-USA Pharmaceuticals, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Haisco-USA Pharmaceuticals, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: William Daley, MD; Haisco-USA Pharmaceuticals, Inc.

• PRS Account: Haisco-USA Pharmaceuticals, Inc.
• Verification Date: October 2023