| Eligibility |
Inclusion Criteria:
1. Healthy males or females with full capacity for civil conduct, aged =18 and =45 years
old. Both male and female subjects should be enrolled;
2. Male subjects should weigh =50 kg, female subjects should weigh =45 kg, and the body
mass index (BMI) should be =19.0 and =26.0 kg/m2;
3. Blood pressure should be between 100-140/60-90 mmHg; heart rate should be between
60-99 bpm; body temperature (ear temperature) should be between 35.5-37.1°C;
respiration rate should be between 12-20 breaths per minute; SpO2 when inhaling should
be =95%;
4. Normal results for physical examinations, laboratory tests (blood routine, blood
biochemistry, urine routine, and blood coagulation routine), 12-lead electrocardiogram
(ECG), chest X-ray, and abdominal B-ultrasound (liver, gallbladder, pancreas, spleen
and kidney), or abnormal results without clinical significance as judged by the
investigator; no significantly potential difficult airway (modified Mallampati score
I-II);
5. No previous history of major organ primary diseases, such as liver, kidneys, digestive
tract, blood, metabolic, and cardiovascular diseases; no history of malignant
hyperthermia and other genetic conditions; no history of mental/neurological diseases;
no history of epilepsy; no contraindications for deep sedation/general anesthesia; no
clinically significant history of anesthesia accidents;
6. Subjects must understand the procedures and methods of this study, and be willing to
provide informed consent and to complete the trial in strict accordance with the
clinical trial protocol.
Exclusion Criteria:
1. Known allergy to excipients in HSK3486 injectable emulsion (soybean oil, glycerin,
triglyceride, egg lecithin, sodium oleate, and sodium hydroxide) or voriconazole, or
contraindications mentioned in the prescribing information of voriconazole ;
2. In receipt of any one of the following medications or treatments during
screening/baseline:
History of drug abuse or any signs of chronic benzodiazepines use (such as insomnia,
anxiety, spasms) within 3 months prior to screening, or a positive urine drug test
during baseline; Participated in clinical trials involving any medications or medical
devices within 3 months prior to screening, or subjects who have participated in 3 or
more drug clinical trials within the past year; In receipt of voriconazole within 4
weeks prior to screening; In receipt of propofol, other sedatives/anesthetics and/or
opioid analgesics or compounds containing analgesics within 1 week prior to baseline;
In receipt of prescription drugs, Chinese herbal medicines, over-the-counter drugs or
food supplements (such as vitamins and calcium supplements) other than contraceptives,
paracetamol, oral non-steroidal anti-inflammatory drugs, topical over-the-counter
preparations, within 2 weeks prior to baseline; in receipt of strong
inhibitors/inducers of CYP enzyme within 7 days prior to baseline, or in receipt of
moderate/weak inhibitors/inducers of CYP enzyme within 3 days prior to baseline (see
Attachment 4 for the inhibitors and inducers); unless the principal investigator (PI)
and the sponsor agree that the medication has no effect on the safety and PK/PD
results of the trial.
3. A history or evidence of any one of the following diseases prior to
screening/baseline:
History of cardiovascular diseases such as: Uncontrolled hypertension [SBP =170 mmHg
and/or DBP =105 mmHg without antihypertensive treatment, or SBP >160 mmHg and/or DBP
>100 mmHg despite antihypertensive treatment], postural hypotension, severe
arrhythmia, heart failure, Adams-Stokes syndrome, unstable angina, myocardial
infarction within 6 months before screening, history of tachycardia/bradycardia
requiring medication, II-III degree atrioventricular block (excluding patients with
pacemakers), or QTcF interval =450 ms (Fridericia's correction formula); Respiratory
insufficiency, history of obstructive pulmonary disease, history of asthma, sleep
apnea; history of failed tracheal intubation; history of bronchospasm requiring
treatment within 3 months prior to screening; acute respiratory infection, and with
obvious symptoms such as fever, wheezing, nasal congestion, or cough within 1 week
prior to baseline; History of GI tract diseases: Gastrointestinal obstruction, active
GI bleed, potential for reflux and aspiration; Serious infection, trauma, or major
surgery within 4 weeks before screening; or acute disease with clinical significance
(determined by the investigator) within 2 weeks before screening, including GI
diseases or infections (such as respiratory or CNS infections); History of eye
diseases: Including glaucoma history and/or family history, history and/or family
history of optic nerve diseases, subjects with proliferative diabetic retinopathy,
history of intraocular surgery (cataract, retina, glaucoma), history of amblyopia,
history of high myopia (=8.0 D).
4. Laboratory results that meet any of the following during screening/baseline:
Positive result for either HBsAg, HCV, HIV, or syphilis; Abnormality in any of the
following indicators of hepatic and renal functions: alanine aminotransferase (ALT) or
aspartate aminotransferase (AST) > 1 x ULN; creatinine > 1 x ULN; total bilirubin TBIL
> 1 x ULN;
5. History of alcohol abuse within 3 months prior to screening, abuse defined as average
of > 2 units of alcohol per day (1 unit = 360 mL beer or 45 mL liquor with40% alcohol
or 150 mL wine), or positive result for breath alcohol test (=20 mg/dl);
6. Smoke more than 5 cigarettes per day and a total of more than 60 cigarettes within 3
months prior to screening;
7. Blood donation or blood loss =200 mL within 30 days prior to screening; plasma
donation or plasma exchange within 7 days prior to screening;
8. Subjects who consume any beverages or food containing alcohol, grapefruit juice or
methylxanthine (such as coffee, tea, coca-cola, chocolate, functional drinks),
participate in strenuous physical activities and other factors that may affect drug
absorption, distribution, metabolism, and excretion within 2 days prior to enrollment;
subjects who are unable to fast for 8 h prior to dose administration;
9. Subjects judged by the investigator to be unsuitable for participating in this trial
for any reason.
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