Clinical trial NCT06170476: A Clinical Trial Evaluating the Efficacy and Safety of HSK21542 in PONV
Official title: A Multicenter, Randomized, Double-blind, Placebo-Controlled Dose-Finding Study of HSK21542 Injection for the Prevention of Postoperative Nausea and Vomiting (PONV)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Postoperative Nausea and Vomiting
Lead sponsor: Sichuan Provincial People's Hospital
Sponsor class: OTHER
First posted: 2023-12-14
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This is a multicenter, randomized, double-blind, placebo-controlled Dose-Finding study. About 200 subjects undergoing elective laparoscopic abdominal or gynecological surgery are planned to be enrolled and randomized into four groups by a ratio of 1:1:1:1.


Eligibility criteria: Inclusion Criteria:

1. Age ≥18 and ≤75 years old, male or female;
2. The American Society of Anesthesiologists (ASA) Class I-III;
3. 18 kg/m2 ≤ BMI ≤ 40 kg/m2;
4. Hospitalized subjects scheduled to undergo elective laparoscopic abdominal or gynecological surgery under general anesthesia for an expected anesthetic time of ≥ 1 h;
5. Subjects with intermediate or high risk (score ≥ 2 points) experiencing PONV judged by the investigator using the Apfel simplified risk score;
6. Subjects who agree to participate in the trial and voluntarily sign the Informed Consent Form (ICF);

Exclusion Criteria:

Prior and concomitant diseases

1. History or evidence of any of the following diseases prior to screening:

   1. Respiratory diseases: severe chronic obstructive pulmonary disease, acute exacerbation of chronic obstructive pulmonary disease, severe airway stenosis, large pharyngolaryngeal mass, (broncho) tracheoesophageal fistula or airway tear, and serious respiratory tract infection within 2 weeks prior to screening;
   2. Central nervous system disorders: subjects with epilepsy, Parkinson's disease, or other central nervous system diseases causing nausea and vomiting, such as craniocerebral injury, intracranial space-occupying lesions, intracranial aneurysms, etc.;
   3. Cardiovascular diseases: subjects with uncontrolled hypertension \[systolic blood pressure (SBP) ≥170 mmHg and/or diastolic blood pressure (DBP) ≥105 mmHg without treatment with antihypertensive medication, or SBP ≥160 mmHg and/or DBP ≥100 mmHg after treatment with antihypertensive medications\], serious cardiac insufficiency ( the New York Heart Association \[NYHA\] Grade III-IV), unstable angina pectoris, acute myocardial infarction, severe arrhythmia, history of tachycardia/bradycardia requiring medical treatment, Grade II-III atrioventricular block (excluding pacemaker use) within 6 months prior to screenin;
   4. Digestive disorders: subjects with intestinal obstruction or other digestive diseases that may cause nausea and vomiting as judged by the investigator;
   5. Patients with a confirmed diagnosis of vestibular function disorder, excluding travel sickness (including but not limited to peripheral vestibular syndrome, central vestibular syndrome, etc.);
   6. Subjects with a history of significant and chronic dizziness.

   Prior and concomitant medications
2. Any of the following medications or treatments have been used at screening:

   1. Subjects who have received antiemetics/medications with antiemetic effects within 24 h before the start of surgery or who have used antiemetics/drugs with antiemetic effects before the start of surgery for no more than 5 half-lives (calculated as the longest time);
   2. Subjects with neoplasm malignant treated with chemotherapy within 4 weeks prior to screening;

   Laboratory and other tests
3. Laboratory test indicators at screening meet the following criteria:

   1. White blood cell count \< 3.0 × 109/L;
   2. Platelet count \< 80 × 109/L;
   3. Hemoglobin\< 70 g/L;
   4. Prolongation of prothrombin time (PT) exceeding the upper limit of normal for 3 seconds;
   5. Prolongation of activated partial thromboplastin time (APTT) exceeding the upper limit of normal for 10 seconds;
   6. Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) \> 3 × ULN;
   7. Total bilirubin \> 2 × ULN;
   8. Blood creatinine \> 2 × ULN;
   9. Fasting serum glucose≥ 11.1 mmol/L;

   Other conditions
4. Subjects anticipated to require continued endotracheal intubation after the end of surgery;
5. Subjects anticipated to require the insertion of nasal or oral gastric tubes after the end of surgery;
6. Subjects with a history of serious drug allergies or those allergic to the investigational drugs specified in the protocol;
7. Subjects with a history of drug abuse, drug addiction, or alcoholism within 3 months prior to screening, where alcoholism is defined as consuming \> 2 units of alcohol on average daily (1 unit = 360 mL of beer with 5% alcohol, 45 mL of liquor with 40% alcohol or 150 mL of wine);
8. Subjects with nausea, retching, or vomiting within 24 h prior to induction of anesthesia (except for those caused by bowel preparation);
9. Subjects who have participated in any investigational trial (defined as receiving investigational drug or placebo) within 3 months prior to screening;
10. Female subjects who are pregnant or breastfeeding; female or male subjects of child-bearing potential are unwilling to use contraception throughout the entire study period and for 3 months after the study completion;
11. Subjects judged by the investigator to be unsuitable for participating in this clinical trial for any other factors.

Primary outcomes:
measure: Complete response
timeFrame: 24 hours after the end of surgery
Secondary outcomes:
measure: Proportion of subjects experiencing nausea within 24 hours after the end of surgery
timeFrame: 24 hours after the end of surgery
measure: Proportion of subjects experiencing significant nausea within 24 hours after the end of surgery
timeFrame: 24 hours after the end of surgery
measure: Proportion of subjects experiencing vomiting within 24 hours after the end of surgery
timeFrame: 24 hours after the end of surgery
measure: Proportion of subjects using rescue medication within 24 hours after the end of surgery
timeFrame: 24 hours after the end of surgery
measure: Time to first occurrence of vomiting or rescue therapy (whichever occurs first) within 24 hours after the end of surger
timeFrame: 24 hours after the end of surgery
measure: The cumulative morphine doses administered within 24 hours after the end of surgery
timeFrame: 24 hours after the end of surgery
measure: PONV Satisfaction Score by Subject and Investigator
timeFrame: 24 hours after the end of surgery
Other outcomes:
Locations:
city: Sichuan
country: China
facility: Sichuan Provincial People's Hospital
Study officials:
References: