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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Sedation or Anesthesia

Intervention / Treatment
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* Drug: HSK3486
* Drug: Propofol


Participation Criteria
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Eligibility Criteria
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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. - Exclusion Criteria: Patients with contraindications to deep sedation/general anesthesia or a history of past sedation/anesthesia accidents; Patient known to be allergic to eggs, soy products, opioids and their antidotes, and propofol; patient having contraindications to propofol, opioids and their antidotes; Patients who have undergone endotracheal intubation and/or mechanical ventilation prior to diagnostic or therapeutic bronchoscopy; Medical history or evidence of any of the following prior to screening/at baseline, which may increase sedation/anesthesia risk: 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)]; 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; 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; History of gastrointestinal diseases: gastrointestinal retention, active hemorrhage, or history of gastroesophageal reflux or obstruction that may lead to aspiration; 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; 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); History of drug abuse within 3 months prior to screening; History of blood transfusion within 14 days prior to screening; Patients with the following respiratory risks during screening/at baseline: Acute asthma attack; Sleep apnea syndrome; History of malignant hyperthermia or family history; History of failed tracheal intubation; Difficult airway (modified Mallampati score ≥ III) as determined by the investigator; Patient who received any of the following medications or treatments during screening/at baseline: Received any investigational drug within 1 month prior to screening; Received propofol, other sedatives/anesthetics, and/or opioid analgesics or compounds containing analgesics within 72 h prior to baseline; Laboratory results meeting any of the following criteria during screening/at baseline, confirmed by re-examination: WBC ≤ 3.0 × 10^9/L; Platelets ≤ 80 × 10^9/L; Hemoglobin ≤ 80 g/L; Prothrombin time ≥ 1.5 × ULN; Activated partial thromboplastin time (aPTT) ≥ 1.5 × ULN; ALT and/or AST ≥ 3 × ULN; Total bilirubin ≥ 1.5 × ULN; Serum creatinine ≥ 1.5 × ULN. 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); Subject judged by the investigator to have any other factors unsuitable for involvement in the study. -

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HSK3486<br>Subjects < 65 years old:0.4mg/kg/0.15mg/kg;Subjects ≥ 65 years old:75% of the dose for subjects < 65 years old. | Drug: HSK3486<br>* Subjects < 65 years old:Initial dose of 0.4 mg/kg followed by 0.15 mg/kg if needed;Subjects ≥ 65 years old:75% of the dose for subjects < 65 years old.<br>|
| Active Comparator: Propofol<br>Subjects < 65 years old:2mg/kg/0.75mg/kg;Subjects≥ 65 years old:75% of the dose for subjects < 65 years old. | Drug: Propofol<br>* Subjects < 65 years old:Initial dose of 2 mg/kg followed by 0.75 mg/kg if needed;Subjects ≥ 65 years old:75% of the dose for subjects < 65 years old.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Success rate of fiberoptic bronchoscopy. A successful diagnosis/treatment should meet both of the following: | Completion of fiberoptic bronchoscopy; No alternative sedation/anesthetic drugs are used, that is, the number of doses of the study drug is ≤ 5 times within any given 15-minute period, starting from the initial administration until the fiberoptic bronchoscopy is completed. | During induction of sedation/anesthetic on day 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to successful sedation/anesthetic induction |  | From the initial administration of the investigational drug to the first time when MOAA/S is ≤1 on day 1 | 
| Time to fully awake | the time from the withdrawal of the bronchoscope or the last dose of the study drug to the first of 3 consecutive MOAA/S scores = 5 | From the last dose of study drug or rescue sedative AND from end of fiberoptic bronchoscopy until the patient has recovered to fully alert on day 1 | 
| Time to discharge | the time from the withdrawal of the bronchoscope or the last dose of the study drug to the first of 3 consecutive Aldrete scores ≥ 9 | Time from the last dose of study drug or rescue sedative and from the end of fiberoptic bronchoscopy until discharge (defined as the ability to walk unassisted) on day 1 | 
| Use of the investigational drug and alternative drugs |  | During induction of sedation/anesthetic on day 1 | 
| Use of questionnaires to estimate sedation/anesthesia satisfaction, including satisfaction assessments of the subject and anesthesiologist |  | During induction of sedation/anesthetic on day 1 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sedation anesthesia fiberoptic bronchoscopy