Overview
Efficacy and Safety of HSK3486 Compared to Propofol for Adults Undergoing Elective Surgery With General Anesthesia
Status:
Not yet recruiting
Not yet recruiting
Trial end date:
2023-05-31
2023-05-31
Target enrollment:
0
0
Participant gender:
All
All
Summary
To demonstrate HSK3486 0.4/0.2 mg/kg (0.4 mg/kg intravenous [IV] slow injection over 30 [±5] seconds for the first dose, an additional 0.2 mg/kg if needed) is non-inferior to propofol 2.0/1.0 mg/kg (2.0 mg/kg IV slow injection over 30 [±5] seconds for first dose, an additional 1.0 mg/kg if needed) in success of induction of general anesthesia in adults undergoing elective surgery.Phase:
Phase 3Accepts Healthy Volunteers?
Accepts Healthy VolunteersDetails
Lead Sponsor:
Haisco-USA Pharmaceuticals, Inc.Treatments:
Propofol
Criteria
Inclusion Criteria:- 1. Subjects undergoing elective surgery (non emergency, non cardiothoracic, and non
intracranial surgery, anticipated to last at least 1 hour) requiring endotracheal
intubation and inhalation general anesthesia during the maintenance period. Duration
of surgery is defined as time from study drug administration to time of transfer from
operating room to recovery room or PACU.
2. Males or females, aged ≥18 years old, with ASA-PS I to IV (Appendix 6). For ASA-PS
IV subjects, clinical status must be optimized at time of preoperative anesthesia
evaluation per judgement of the anesthesiologist.
3. BMI ≥18 kg/m2. 4. Vital signs at screening: RR ≥10 and ≤24 breaths/min; SpO2≥92% in
ambient air; SBP ≥90 and ≤160 mmHg; DBP ≥55 and ≤100 mmHg; HR ≥55 (or ≥50 if subjects
are on beta blockers) and ≤100 beats/min.
5. For all women of childbearing potential, negative serum pregnancy test at screening
and must have negative urine pregnancy test at baseline (Day 1). Additionally, women
of childbearing potential* must agree to use effective contraception as defined in
7.3.4 from the time of consent until 30 days post study drug administration.
6. Capable of understanding the procedures and methods of this study, willing to sign
an Informed Consent Form, and able to complete this study in strict compliance with
the study protocol.
7. Willing to comply with the site's COVID guidelines and testing requirements as
applicable.
8. Patients with psychiatric diseases (schizophrenia, mania) must be considered stable
on treatment (with SSRIs, SNRIs, TCAs, and MAOIs) and no hospitalizations and urgent
care for at least 1 year.
Women NOT of childbearing potential are defined as those who have been surgically
sterilized (hysterectomy, bilateral salpingo-oophorectomy) or who are postmenopausal
(defined 12 months since last regular menses).
Exclusion Criteria:
- 1. Contraindications to deep sedation/general anesthesia or a history of adverse
reaction to sedation/general anesthesia.
2. Known to be allergic to eggs, soy products, opioids and their antidotes, or
propofol; subject having contraindications to propofol, opioids, and their antidotes.
3. Medical condition or evidence of increased sedation/general anesthesia risk as
follows:
1. Cardiovascular disorders: uncontrolled hypertension (SBP>160 mmHg and/or DBP >100
mmHg) with or without antihypertensive therapy (antihypertensive therapy should
be stable for 1 month prior to screening), serious arrhythmia (including the
subjects with implanted pace makers), unstable heart failure, Adams-Stokes
syndrome (i.e., syncope or near syncope due to cardiac arrythmia), unstable
angina, myocardial infarction occurring within 6 months prior to screening,
history of tachycardia/bradycardia requiring medications, third degree
atrioventricular block or QT interval corrected for HR using Fridericia's formula
(QTcF)≥450ms for males and ≥470ms for females.
2. History of severe obstructive lung disease (i.e., forced expiratory volume in 1
second [FEV1] <50% predicted), history of bronchospasm requiring treatment in a
hospital emergency room or hospitalization occurring within 3 months prior to
screening, developing acute respiratory tract infection within 2 weeks prior to
baseline (such as symptoms of fever, shortness of breath, wheezing, nasal
congestion, and cough).
3. Cerebrovascular disease: subject with a history of serious craniocerebral injury,
convulsion, seizure disorder, intracranial hypertension, cerebral aneurysm, or
stroke.
4. Patients with psychiatric diseases (schizophrenia, mania) who have not been on a
stable treatment regimen (with SSRIs, SNRIs, TCAs, MAOIs) for at least 1 year or
who have been hospitalized or had emergent/urgent care within the past year.
5. Uncontrolled clinically significant conditions of liver (e.g., severe hepatic
insufficiency defined as Childs-Pugh class C), kidney, gastrointestinal tract,
blood system, nervous system, or metabolic system diseases, judged by the
investigator to be unsuitable for involvement in the study.
6. Known glycosylated hemoglobin (HbA1c) greater than or equal to 10%.
7. Known thyroid-stimulating hormone (TSH) value 10% outside the normal range or on
thyroid replacement therapy with a known free T-4 level outside the normal range.
8. History of alcohol abuse within 3 months prior to screening, where alcohol abuse
refers to daily alcohol drinking >2 units (1 unit = 360 mL of beer or 45 mL of
spirit with a strength of 40% or 150 mL of wine).
9. History of drug abuse that, in the opinion of the investigator, may confound the
interpretation of safety or efficacy in a study subject.
Diagnosis and main criteria for inclusion and exclusion:
Inclusion criteria:
Subjects must satisfy all of the following criteria at the screening visit:
1. Subjects undergoing elective surgery (non emergency, non cardiothoracic, and non
intracranial surgery, anticipated to last at least 1 hour) requiring endotracheal
intubation and inhalation general anesthesia during the maintenance period. Duration
of surgery is defined as time from study drug administration to time of transfer from
operating room to recovery room or PACU.
2. Males or females, aged ≥18 years old, with ASA-PS I to IV (Appendix 6). For ASA-PS IV
subjects, clinical status must be optimized at time of preoperative anesthesia
evaluation per judgement of the anesthesiologist.
3. BMI ≥18 kg/m2.
4. Vital signs at screening: RR ≥10 and ≤24 breaths/min; SpO2≥92% in ambient air; SBP ≥90
and ≤160 mmHg; DBP ≥55 and ≤100 mmHg; HR ≥55 (or ≥50 if subjects are on beta blockers)
and ≤100 beats/min.
5. For all women of childbearing potential, negative serum pregnancy test at screening
and must have negative urine pregnancy test at baseline (Day 1). Additionally, women
of childbearing potential* must agree to use effective contraception as defined in
7.3.4 from the time of consent until 30 days post study drug administration.
6. Capable of understanding the procedures and methods of this study, willing to sign an
Informed Consent Form, and able to complete this study in strict compliance with the
study protocol.
7. Willing to comply with the site's COVID guidelines and testing requirements as
applicable.
8. Patients with psychiatric diseases (schizophrenia, mania) must be considered stable on
treatment (with SSRIs, SNRIs, TCAs, and MAOIs) and no hospitalizations and urgent care
for at least 1 year.
- Women NOT of childbearing potential are defined as those who have been surgically
sterilized (hysterectomy, bilateral salpingo-oophorectomy) or who are
postmenopausal (defined 12 months since last regular menses).
Exclusion criteria:
Subjects will be excluded from the study if they satisfy any of the following criteria at
the screening visit:
1. Contraindications to deep sedation/general anesthesia or a history of adverse reaction
to sedation/general anesthesia.
2. Known to be allergic to eggs, soy products, opioids and their antidotes, or propofol;
subject having contraindications to propofol, opioids, and their antidotes.
3. Medical condition or evidence of increased sedation/general anesthesia risk as
follows:
1. Cardiovascular disorders: uncontrolled hypertension (SBP>160 mmHg and/or DBP >100
mmHg) with or without antihypertensive therapy (antihypertensive therapy should
be stable for 1 month prior to screening), serious arrhythmia (including the
subjects with implanted pace makers), unstable heart failure, Adams-Stokes
syndrome (i.e., syncope or near syncope due to cardiac arrythmia), unstable
angina, myocardial infarction occurring within 6 months prior to screening,
history of tachycardia/bradycardia requiring medications, third degree
atrioventricular block or QT interval corrected for HR using Fridericia's formula
(QTcF)≥450ms for males and ≥470ms for females.
2. History of severe obstructive lung disease (i.e., forced expiratory volume in 1
second [FEV1] <50% predicted), history of bronchospasm requiring treatment in a
hospital emergency room or hospitalization occurring within 3 months prior to
screening, developing acute respiratory tract infection within 2 weeks prior to
baseline (such as symptoms of fever, shortness of breath, wheezing, nasal
congestion, and cough).
3. Cerebrovascular disease: subject with a history of serious craniocerebral injury,
convulsion, seizure disorder, intracranial hypertension, cerebral aneurysm, or
stroke.
4. Patients with psychiatric diseases (schizophrenia, mania) who have not been on a
stable treatment regimen (with SSRIs, SNRIs, TCAs, MAOIs) for at least 1 year or
who have been hospitalized or had emergent/urgent care within the past year.
5. Uncontrolled clinically significant conditions of liver (e.g., severe hepatic
insufficiency defined as Childs-Pugh class C), kidney, gastrointestinal tract,
blood system, nervous system, or metabolic system diseases, judged by the
investigator to be unsuitable for involvement in the study.
6. Known glycosylated hemoglobin (HbA1c) greater than or equal to 10%.
7. Known thyroid-stimulating hormone (TSH) value 10% outside the normal range or on
thyroid replacement therapy with a known free T-4 level outside the normal range.
8. History of alcohol abuse within 3 months prior to screening, where alcohol abuse
refers to daily alcohol drinking >2 units (1 unit = 360 mL of beer or 45 mL of
spirit with a strength of 40% or 150 mL of wine).
9. History of drug abuse that, in the opinion of the investigator, may confound the
interpretation of safety or efficacy in a study subject.
4. Management risks of respiratory tract and judged by the investigator to be unsuitable
for inclusion in the study as follows:
1. Asthma must be stable: stable doses of asthma medications for the past 6 months,
no requirement for rescue inhalers or oral steroids within past 6 months, not
evaluated in emergency department, urgent care, or hospitalized for an asthma
attack within past 1 year.
2. History (or family history) of malignant hyperthermia.
3. Any previous failure of tracheal intubation.
4. Judged to have a difficult airway for endotracheal intubation in the opinion of
the Investigator based on parameters such as modified Mallampati score (Grade III
or IV [Appendix 7], neck mobility, short thyromental distance, and/or history of
difficult intubation).
5. Any medication that has the potential to interact synergistically with propofol or
HSK3486, including but not limited to all sedatives and hypnotics (e.g.,
benzodiazepines and opioids) taken within 5 half-lives prior to Day 1.
6. Taking valproic acid (Depakote) within 1 week prior to Day 1; taking UGT1A9 inhibitors
(Appendix 8), including but not limited to phenytoin, fosphenytoin, mefenamic acid,
sorafenib, deferasirox, rifampicin, within 1 week prior to Day 1.
7. Laboratory parameters measured at screening with the following levels:
1. Neutrophil count ≤1.5 x 109/L
2. Platelet count <80 x 109/L
3. Hemoglobin <90 g/L (without blood transfusion within 14 days)
4. Alanine transaminase and/or aspartate transaminase ≥2.0 x upper limit of normal
(ULN)
5. Total bilirubin ≥2.0 x ULN
6. Severe renal impairment defined by creatinine clearance (CrCl) ≤30 mL/min
8. 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).
9. Judged by the investigator to have any other factors that make the subject unsuitable
for participation in the study.