Anesthesia
Conditions
Keywords
Anesthesia, Elective surgery, Propofol
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.
Interventions
DRUGHSK3486
HSK3486 for induction of general anesthesia.
DRUGPropofol
Propofol for induction of general anesthesia.
Sponsors
Haisco-USA Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Successful Anesthesia Induction | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Subjects' NRS Pain Score | Up to 8 hours | 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. | 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. | 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. | From end 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Time to the Disappearance of Eyelash Reflex | From end 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 | 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 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| HSK3486 HSK3486 for induction of general anesthesia.
HSK3486: HSK3486 for induction of general anesthesia. | 168 |
| Propofol Propofol for induction of general anesthesia.
Propofol: Propofol for induction of general anesthesia. | 83 |
| Total | 251 |
Baseline characteristics
| Characteristic | HSK3486 | Propofol | Total |
|---|---|---|---|
| Age, Customized Age Group (Years) <65 | 141 Participants | 69 Participants | 210 Participants |
| Age, Customized Age Group (Years) ≥65 | 27 Participants | 14 Participants | 41 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 45 Participants | 23 Participants | 68 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 118 Participants | 58 Participants | 176 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 5 Participants | 2 Participants | 7 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 0 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 36 Participants | 12 Participants | 48 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 5 Participants | 0 Participants | 5 Participants |
| Race (NIH/OMB) White | 121 Participants | 71 Participants | 192 Participants |
| Sex: Female, Male Female | 119 Participants | 57 Participants | 176 Participants |
| Sex: Female, Male Male | 49 Participants | 26 Participants | 75 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 168 | 0 / 83 |
| other Total, other adverse events | 47 / 168 | 27 / 83 |
| serious Total, serious adverse events | 0 / 168 | 3 / 83 |
Outcome results
Primary
Number of Participants With Successful Anesthesia Induction
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)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| HSK3486 | Number of Participants With Successful Anesthesia Induction | 163 Participants |
| Propofol | Number of Participants With Successful Anesthesia Induction | 81 Participants |
Secondary
Proportion of Subjects With Any Injection-site Pain on Numeric Rating Scale.
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)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| HSK3486 | Proportion of Subjects With Any Injection-site Pain on Numeric Rating Scale. | 30 Participants |
| Propofol | Proportion of Subjects With Any Injection-site Pain on Numeric Rating Scale. | 64 Participants |
Secondary
Proportion of Subjects With Successful Induction Who Maintain the Desired Depth of Anesthesia for General Elective Surgery, AND Without Significant Cardiac and Respiratory Depression.
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.
Population: Induction of General Anesthesia
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| HSK3486 | Proportion of Subjects With Successful Induction Who Maintain the Desired Depth of Anesthesia for General Elective Surgery, AND Without Significant Cardiac and Respiratory Depression. | Successful Induction | 163 Participants |
| HSK3486 | Proportion of Subjects With Successful Induction Who Maintain the Desired Depth of Anesthesia for General Elective Surgery, AND Without Significant Cardiac and Respiratory Depression. | Failed Induction | 5 Participants |
| Propofol | Proportion of Subjects With Successful Induction Who Maintain the Desired Depth of Anesthesia for General Elective Surgery, AND Without Significant Cardiac and Respiratory Depression. | Successful Induction | 81 Participants |
| Propofol | Proportion of Subjects With Successful Induction Who Maintain the Desired Depth of Anesthesia for General Elective Surgery, AND Without Significant Cardiac and Respiratory Depression. | Failed Induction | 2 Participants |
Secondary
Subjects' NRS Pain Score
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 8 hours
Population: Full Analysis Set (FAS): All randomized subjects who have received at least 1 dose of the study drug (HSK3486 or propofol).
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| HSK3486 | Subjects' NRS Pain Score | Proportion of NRS ≥ 1 pain score on Day 1 | Proportion of NRS ≥1 and <4 pain score | 20 Participants |
| HSK3486 | Subjects' NRS Pain Score | Proportion of NRS ≥ 1 pain score on Day 1 | Proportion of NRS ≥4 pain score | 10 Participants |
| HSK3486 | Subjects' NRS Pain Score | Proportion of NRS ≥ 1 pain score on Day 1 | Proportion of NRS = 0 Pain score | 137 Participants |
| HSK3486 | Subjects' NRS Pain Score | Proportion of NRS ≥ 1 pain score on Day 1 | Missing NRS | 1 Participants |
| HSK3486 | Subjects' NRS Pain Score | Proportion of NRS ≥ 1 pain Score in PACU | Proportion of NRS ≥1 and <4 pain score | 27 Participants |
| HSK3486 | Subjects' NRS Pain Score | Proportion of NRS ≥ 1 pain Score in PACU | Proportion of NRS ≥4 pain score | 19 Participants |
| HSK3486 | Subjects' NRS Pain Score | Proportion of NRS ≥ 1 pain Score in PACU | Proportion of NRS = 0 Pain score | 113 Participants |
| HSK3486 | Subjects' NRS Pain Score | Proportion of NRS ≥ 1 pain Score in PACU | Missing NRS | 9 Participants |
| Propofol | Subjects' NRS Pain Score | Proportion of NRS ≥ 1 pain Score in PACU | Missing NRS | 6 Participants |
| Propofol | Subjects' NRS Pain Score | Proportion of NRS ≥ 1 pain score on Day 1 | Proportion of NRS ≥1 and <4 pain score | 13 Participants |
| Propofol | Subjects' NRS Pain Score | Proportion of NRS ≥ 1 pain Score in PACU | Proportion of NRS ≥1 and <4 pain score | 17 Participants |
| Propofol | Subjects' NRS Pain Score | Proportion of NRS ≥ 1 pain score on Day 1 | Proportion of NRS ≥4 pain score | 51 Participants |
| Propofol | Subjects' NRS Pain Score | Proportion of NRS ≥ 1 pain Score in PACU | Proportion of NRS = 0 Pain score | 21 Participants |
| Propofol | Subjects' NRS Pain Score | Proportion of NRS ≥ 1 pain score on Day 1 | Proportion of NRS = 0 Pain score | 19 Participants |
| Propofol | Subjects' NRS Pain Score | Proportion of NRS ≥ 1 pain Score in PACU | Proportion of NRS ≥4 pain score | 39 Participants |
| Propofol | Subjects' NRS Pain Score | Proportion of NRS ≥ 1 pain score on Day 1 | Missing NRS | 0 Participants |
Secondary
Time to Successful Induction of General Anesthesia.
Time from the end of the first administration of the study drug to MOAA/S ≤1.
Time frame: From end of drug administration to MOAA/S ≤1 (up to 5 minutes)
Population: 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 | Measure | Value (MEDIAN) |
|---|---|---|
| HSK3486 | Time to Successful Induction of General Anesthesia. | 0.75 minutes |
| Propofol | Time to Successful Induction of General Anesthesia. | 0.62 minutes |
Other Pre-specified
Number of Participants That Failed to Meet Successful Induction of General Anesthesia
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)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| HSK3486 | Number of Participants That Failed to Meet Successful Induction of General Anesthesia | 5 Participants |
| Propofol | Number of Participants That Failed to Meet Successful Induction of General Anesthesia | 2 Participants |
95% CI: [-0.054, 0.042]Farrington-Manning method
Other Pre-specified
Time to the Disappearance of Eyelash Reflex
Time from the end of the first administration of the study drug to the disappearance of eyelash reflex.
Time frame: From end of drug administration to disappearance of eyelash reflex (up to 5 minutes)
Population: 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 | Measure | Value (MEDIAN) |
|---|---|---|
| HSK3486 | Time to the Disappearance of Eyelash Reflex | 0.92 minutes |
| Propofol | Time to the Disappearance of Eyelash Reflex | 0.80 minutes |