A Trial Evaluating the Efficacy and Safety of HSK3486 Injectable Emulsion in Subjects Undergoing Fiberoptic Bronchoscopy

A Multi-Center, Randomized, Double-Blind, Propofol-Controlled Phase III Clinical Trial Evaluating the Efficacy and Safety of HSK3486 Injectable Emulsion for the Induction of Sedation/Anesthesia in Subjects Undergoing Fiberoptic Bronchoscopy

This is a Multi-Center, Randomized, Double-Blind, Propofol-Controlled Phase III Clinical Trial. Around 260 eligible subjects are planned to be enrolled and randomized in a 1:1 ratio to either the HSK3486 arm or propofol arm. The main objective is to evaluate the efficacy of HSK3486 vs. propofol for the induction of sedation/anesthesia in subjects undergoing fiberoptic bronchoscopy.

Inclusion Criteria:

1.Subjects receiving laryngeal mask airway-assisted diagnostic and/or therapeutic fiberoptic bronchoscopy; 2.Male or female, ASA I-III, ≥ 18 and < 80 years old; 3.Body mass index (BMI) ≥ 18 and ≤ 30 kg/m2; 4.Respiratory rate ≥ 10 and ≤ 24 bpm; SpO2 ≥ 93%; SBP ≥ 90 mmHg; DBP ≥ 55 mmHg; HR ≥ 50 and ≤ 100 bpm during screening and baseline periods; 5.Capable of understanding the procedure and method of this study, willing to sign an informed consent form and to complete this study in strict accordance with the study protocol.

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Exclusion Criteria:

1. Patients with contraindications to deep sedation/general anesthesia or a history of past sedation/anesthesia accidents;

2. Patient known to be allergic to eggs, soy products, opioids and their antidotes, and propofol; patient having contraindications to propofol, opioids and their antidotes;

3. Patients who have undergone endotracheal intubation and/or mechanical ventilation prior to diagnostic or therapeutic bronchoscopy;

4. Medical history or evidence of any of the following prior to screening/at baseline, which may increase sedation/anesthesia risk:

   1. History of cardiovascular diseases: uncontrolled hypertension [systolic blood pressure (SBP) ≥170 mmHg and/or diastolic blood pressure (DBP) ≥105 mmHg without treatment, or SBP > 160 mmHg and/or DBP >100 mmHg after antihypertensive treatment], aneurysm, severe arrhythmia, heart failure, Adams-stokes syndrome, New York Heart Association (NYHA) Class ≥ III, severe superior vena cava syndrome, pericardial effusion, acute myocardial ischemia, unstable angina, myocardial infarction within 6 months before screening, history of tachycardia/bradycardia requiring medical treatment, II-III degree atrioventricular block (excluding patients with pacemakers) or QTcF interval ≥ 450 ms [during screening only (corrected using Fredericia's formula1)];
   2. History of respiratory diseases: severe chronic obstructive pulmonary disease, acute exacerbation of chronic obstructive pulmonary disease, severe airway stenosis, throat mass, history of tracheoesophageal fistula or airway tear, severe respiratory infection within 2 weeks prior to screening;
   3. History of neurological and psychiatric disorders: craniocerebral injury, possible convulsions, intracranial hypertension, cerebral aneurysms, history of cerebrovascular accidents; schizophrenia, mania, insanity, long-term use of psychotropic drugs, and history of cognitive dysfunction;
   4. History of gastrointestinal diseases: gastrointestinal retention, active hemorrhage, or history of gastroesophageal reflux or obstruction that may lead to aspiration;
   5. History of uncontrolled clinically significant liver, kidney, blood system, nervous system or metabolic system diseases judged by the investigator to be probably unsuitable for involvement in the study;
   6. 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 with 40% alcohol or 150 mL wine);
   7. History of drug abuse within 3 months prior to screening;
   8. History of blood transfusion within 14 days prior to screening;

5. Patients with the following respiratory risks during screening/at baseline:

   1. Acute asthma attack;
   2. Sleep apnea syndrome;
   3. History of malignant hyperthermia or family history;
   4. History of failed tracheal intubation;
   5. Difficult airway (modified Mallampati score ≥ III) as determined by the investigator;

6. Patient who received any of the following medications or treatments during screening/at baseline:

   1. Received any investigational drug within 1 month prior to screening;
   2. Received propofol, other sedatives/anesthetics, and/or opioid analgesics or compounds containing analgesics within 72 h prior to baseline;

7. Laboratory results meeting any of the following criteria during screening/at baseline, confirmed by re-examination:

   1. WBC ≤ 3.0 × 10^9/L;
   2. Platelets ≤ 80 × 10^9/L;
   3. Hemoglobin ≤ 80 g/L;
   4. Prothrombin time ≥ 1.5 × ULN;
   5. Activated partial thromboplastin time (aPTT) ≥ 1.5 × ULN;
   6. ALT and/or AST ≥ 3 × ULN;
   7. Total bilirubin ≥ 1.5 × ULN;
   8. Serum creatinine ≥ 1.5 × ULN.

8. Women who are pregnant or breastfeeding; women of child-bearing potential or men who are unwilling to use contraception during the trial; or subjects who are planning pregnancy within 3 month after the completion of the trial (including male subjects);

9. Subject judged by the investigator to have any other factors unsuitable for involvement in the study.

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