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.

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Anesthesia
• Interventions: Drug: HSK3486; Drug: Propofol
• Enrollment: 255

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	HSK3486	Propofol
Arm/Group Description	HSK3486 for induction of general anesthesia. HSK3486: HSK3486 for induction of general anesthesia.	Propofol for induction of general anesthesia. Propofol: Propofol for induction of general anesthesia.
Period Title: Overall Study
Started	170	85
Completed	168	83
Not Completed	2	2

Baseline Characteristics

Arm/Group Title		HSK3486	Propofol	Total
Arm/Group Description		HSK3486 for induction of general anesthesia. HSK3486: HSK3486 for induction of general anesthesia.	Propofol for induction of general anesthesia. Propofol: Propofol for induction of general anesthesia.	Total of all reporting groups
Overall Number of Baseline Participants		168	83	251
Baseline Analysis Population Description		[Not Specified]
Age, Customized; Measure Type: Count of Participants; Unit of measure: Participants
Age Group (Years)	Number Analyzed	168 participants	83 participants	251 participants
	≥65	27 16.1%	14 16.9%	41 16.3%
	<65	141 83.9%	69 83.1%	210 83.7%
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	168 participants	83 participants	251 participants
	Female	119 70.8%	57 68.7%	176 70.1%
	Male	49 29.2%	26 31.3%	75 29.9%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	168 participants	83 participants	251 participants
	Hispanic or Latino	45 26.8%	23 27.7%	68 27.1%
	Not Hispanic or Latino	118 70.2%	58 69.9%	176 70.1%
	Unknown or Not Reported	5 3.0%	2 2.4%	7 2.8%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	168 participants	83 participants	251 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%
	Asian	4 2.4%	0 0.0%	4 1.6%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%
	Black or African American	36 21.4%	12 14.5%	48 19.1%
	White	121 72.0%	71 85.5%	192 76.5%
	More than one race	2 1.2%	0 0.0%	2 0.8%
	Unknown or Not Reported	5 3.0%	0 0.0%	5 2.0%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	HSK3486	Propofol
Arm/Group Description:	HSK3486 for induction of general anesthesia. HSK3486: HSK3486 for induction of general anesthesia.	Propofol for induction of general anesthesia. Propofol: Propofol for induction of general anesthesia.
Overall Number of Participants Analyzed	168	83
Measure Type: Count of Participants; Unit of Measure: Participants
	163 97.0%	81 97.6%

2. Secondary Outcome

Title	Subjects' NRS Pain Score
Description	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.
Time Frame	Up to 5 minutes

Outcome Measure Data

Analysis Population Description

Day 1: 1/168 subjects not assessed in HSK3486; PACU: 9/168 subjects not assessed in HSK3486; 6/83 subjects not assessed in Propofol

Arm/Group Title		HSK3486	Propofol
Arm/Group Description:		HSK3486 for induction of general anesthesia. HSK3486: HSK3486 for induction of general anesthesia.	Propofol for induction of general anesthesia. Propofol: Propofol for induction of general anesthesia.
Overall Number of Participants Analyzed		168	83
Measure Type: Count of Participants; Unit of Measure: Participants
Proportion of NRS ≥ 1 pain score on Day 1	Number Analyzed	167 participants	83 participants
	Proportion of NRS ≥1 and <4 pain score	20 12.0%	13 15.7%
	Proportion of NRS ≥4 pain score	10 6.0%	51 61.4%
	Proportion of NRS = 0 Pain score	137 82.0%	19 22.9%
Proportion of NRS ≥ 1 pain Score in PACU	Number Analyzed	159 participants	77 participants
	Proportion of NRS ≥1 and <4 pain score	27 17.0%	17 22.1%
	Proportion of NRS ≥4 pain score	19 11.9%	39 50.6%
	Proportion of NRS = 0 Pain score	113 71.1%	21 27.3%

3. Secondary Outcome

Title	Proportion of Subjects With Successful Induction Who Maintain the Desired Depth of Anesthesia for General Elective Surgery, AND Without Significant Cardiac and Respiratory Depression.
Description	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.
Time Frame	15 minutes from end of drug administration.

Outcome Measure Data

Analysis Population Description

Induction of General Anesthesia

Arm/Group Title	HSK3486	Propofol
Arm/Group Description:	HSK3486 for induction of general anesthesia. HSK3486: HSK3486 for induction of general anesthesia.	Propofol for induction of general anesthesia. Propofol: Propofol for induction of general anesthesia.
Overall Number of Participants Analyzed	168	83
Measure Type: Count of Participants; Unit of Measure: Participants
Successful Induction	163 97.0%	81 97.6%
Failed Induction	5 3.0%	2 2.4%

4. Secondary Outcome

Title	Proportion of Subjects With Any Injection-site Pain on Numeric Rating Scale.
Description	The proportion of subjects with any injection-site pain at time of drug administration on the Numeric Rating Scale (NRS ≥1).
Time Frame	From start of drug administration to MOAA/S ≤1 (up to 5 minutes)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	HSK3486	Propofol
Arm/Group Description:	HSK3486 for induction of general anesthesia. HSK3486: HSK3486 for induction of general anesthesia.	Propofol for induction of general anesthesia. Propofol: Propofol for induction of general anesthesia.
Overall Number of Participants Analyzed	167	83
Measure Type: Count of Participants; Unit of Measure: Participants
	30 18.0%	64 77.1%

5. Secondary Outcome

Title	Time to Successful Induction of General Anesthesia.
Description	Time from the end of the first administration of the study drug to MOAA/S ≤1.
Time Frame	From start of drug administration to MOAA/S ≤1 (up to 5 minutes)

Outcome Measure Data

Analysis Population Description

Time to successful induction of general anesthesia was defined as the time from the end of first administration of the study drug to the time when MOAA/S was ≤1.

Arm/Group Title	HSK3486	Propofol
Arm/Group Description:	HSK3486 for induction of general anesthesia. HSK3486: HSK3486 for induction of general anesthesia.	Propofol for induction of general anesthesia. Propofol: Propofol for induction of general anesthesia.
Overall Number of Participants Analyzed	168	83
Median (95% Confidence Interval); Unit of Measure: minutes
	0.75; (0.6167 to 0.9000)	0.62; (0.5167 to 0.8000)

6. Other Pre-specified Outcome

Title	Time to the Disappearance of Eyelash Reflex
Description	Time from the end of the first administration of the study drug to the disappearance of eyelash reflex.
Time Frame	From start of drug administration to disappearance of eyelash reflex (up to 5 minutes)

Outcome Measure Data

Analysis Population Description

Time to loss of eyelash reflex was defined as the time from the end of the first administration of the study drug to the time when eyelash reflex was lost.

Arm/Group Title	HSK3486	Propofol
Arm/Group Description:	HSK3486 for induction of general anesthesia. HSK3486: HSK3486 for induction of general anesthesia.	Propofol for induction of general anesthesia. Propofol: Propofol for induction of general anesthesia.
Overall Number of Participants Analyzed	168	83
Median (95% Confidence Interval); Unit of Measure: minutes
	0.92; (0.8333 to 1.0000)	0.80; (0.7333 to 1.0000)

7. Other Pre-specified Outcome

Title	Number of Participants That Failed to Meet Successful Induction of General Anesthesia
Description	Failed to meet successful induction of general anesthesia defined by the 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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	HSK3486	Propofol
Arm/Group Description:	HSK3486 for induction of general anesthesia. HSK3486: HSK3486 for induction of general anesthesia.	Propofol for induction of general anesthesia. Propofol: Propofol for induction of general anesthesia.
Overall Number of Participants Analyzed	168	83
Measure Type: Count of Participants; Unit of Measure: Participants
	5 3.0%	2 2.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	HSK3486, Propofol
	Comments	[Not Specified]
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority margin equals to -8%
Statistical Test of Hypothesis	P-Value	[Not Specified]
	Comments	Non-inferiority margin equals to -8%: 95% CI; (-5.4%, 4.2%)
	Method	Farrington-Manning method
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	-0.0057
	Confidence Interval	(2-Sided) 95%; -0.054 to 0.042
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.0246
	Estimation Comments	[Not Specified]

Adverse Events

Time Frame	Adverse event reporting begins from the time of informed consent and ends 30 days after the last dose of study drug.
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	HSK3486		Propofol
Arm/Group Description	HSK3486 for induction of general anesthesia. HSK3486: HSK3486 for induction of general anesthesia.		Propofol for induction of general anesthesia. Propofol: Propofol for induction of general anesthesia.
All-Cause Mortality
	HSK3486		Propofol
	Affected / at Risk (%)		Affected / at Risk (%)
Total	0/168 (0.00%)		0/83 (0.00%)
Serious Adverse Events
	HSK3486		Propofol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/168 (0.00%)		3/83 (3.61%)
Cardiac disorders
Pulmonary Embolism † 1	0/168 (0.00%)	0	1/83 (1.20%)	83
Gastrointestinal disorders
Abdominal Wall Haematoma † 1	0/168 (0.00%)	0	1/83 (1.20%)	83
Musculoskeletal and connective tissue disorders
Femur Fracture † 1	0/168 (0.00%)	0	1/83 (1.20%)	83
1 Term from vocabulary, The MedDRA V 25; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	HSK3486		Propofol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	47/168 (27.98%)		27/83 (32.53%)
Gastrointestinal disorders
Nausea † 1	46/168 (27.38%)		27/83 (32.53%)
Injury, poisoning and procedural complications
Procedural Pain † 1	32/168 (19.05%)		19/83 (22.89%)
Vascular disorders
Hypotension † 1	47/168 (27.98%)		27/83 (32.53%)
1 Term from vocabulary, The MedDRA Version 2; † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Site PI restriction

Results Point of Contact

• Name/Title: Yu-Ling Lai Senior Director Clinical Operations
• Organization: Haisco USA Pharmaceutical Inc.
• Phone: 1 732-26-4759
• EMail: Yuling.lai@Haisco-usa.com

• Responsible Party: Haisco-USA Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT04711837
• Other Study ID Numbers: HSK3486-304
• First Submitted: January 12, 2021
• First Posted: January 15, 2021
• Results First Submitted: March 28, 2023
• Results First Posted: May 26, 2023
• Last Update Posted: October 6, 2023