Phase II Clinical Study of the Efficacy and Safety of HSK55718 in the Treatment of Abdominal Postoperative Pain

Официальное название

To Evaluate the Efficacy and Safety of HSK55718 for Injection in Patients With Abdominal Postoperative Pain: a Multicenter, Randomized, Double-blind, Placebo/Positive Control Phase II Clinical Trial.

Обзор

A multicenter, randomized, double-blind, placebo-controlled, and positive-controlled phase II clinical trial was conducted to evaluate the efficacy and safety of HSK55718 injection for postoperative analgesia in patients undergoing abdominal surgery. The primary objective was to evaluate the efficacy of HSK55718 for postoperative analgesia after abdominal surgery. The secondary objective was to evaluate the safety and pharmacokinetic profile of TRD303 solution for postoperative analgesia after abdominal surgery.

Вмешательства

• Препарат Low dose HSK55718
  NRS pain score was performed immediately after emergence from anesthesia. After the postoperative NRS pain score ≥4, the first dose of HSK55718 injection 15mg was given intravenously, and then 7.5mg HSK55718 injection or normal saline was given intermittently every 6 hours
• Препарат Medium Dose HSK55718
  NRS pain score was performed immediately after emergence from anesthesia. After the postoperative NRS pain score ≥4, the first dose of HSK55718 injection 60mg was given intravenously, and then 30mg HSK55718 injection or normal saline was given intermittently every 6 hours.
• Препарат High dose HSK55718
  NRS pain score was performed immediately after emergence from anesthesia. After the postoperative NRS pain score ≥4, the first dose of HSK55718 injection 120mg was given intravenously, and then 60mg HSK55718 injection or normal saline was given intermittently every 6 hours
• Препарат Morphine
  NRS pain score was performed immediately after emergence from anesthesia. After the postoperative NRS pain score ≥4, morphine injection 2mg was given intravenously as the first dose, and then morphine injection 2mg was given intermittently every 6 hours
• Препарат Normal saline solution
  NRS pain score was performed immediately after emergence from anesthesia. After the postoperative NRS pain score ≥4, normal saline solution was given intravenously as the first dose, and then normal saline solution was given intermittently every 6 hours

Первичные конечные точки

• The time-weighted summed pain intensity differences over 24 h (SPID0-24 h) at rest [Срок оценки: From administration until 24 hours after administration]

Вторичные конечные точки (8)

• the time-weighted summed pain intensity differences (SPID) at rest [Срок оценки: From administration until 12 hours, 48 hours after administration, from 12 hours to 24 hours and 24 hours to 48 hours after administration.]
• Pain intensity differences (PID) [Срок оценки: From administration until 48 hours after administration]
• The proportion of NRS pain score ≤3 [Срок оценки: From administration until 48 hours after administration]
• Time to onset [Срок оценки: From administration until 12 hours after administration]
• Cumulative use of rescue analgesics during each period [Срок оценки: From the time of administration to 24 hours and 48 hours after administration]
• Time of first sufentanil rescue analgesia [Срок оценки: From administration until 48 hours after administration]
• Proportion of rescue analgesia [Срок оценки: From administration until 48 hours after administration]
• Postoperative analgesia satisfaction score [Срок оценки: From administration until 48 hours after administration]

Критерии участия

Критерии включения

• Fully understand, voluntarily participate in this study and sign the informed consent;
• Age ≥18 years old, both sexes;
• Undergo elective abdominal surgery (open or laparoscopic) with a (estimated) duration of ≥1 hour under general anesthesia;
• 18.0 kg/m2≤ body mass index (BMI) ≤30.0 kg/m2
• American Society of Anesthesiologists (ASA) grade ⅰ-ⅱ;
• NRS≥4 in the resting state at any time within 4 hours after the end of surgery;
• Be able to comply with the follow-up schedule and other program requirements;
• Participants agreed to use highly effective contraception for the entire duration of the study, from the time they signed the ICF until 3 months after the last dose of the investigational product was administered.

Критерии исключения

1\. Disease status

• History of vestibular dysfunction or dizziness, nausea, retching or vomiting within 1 week before screening;
• Cardiovascular history: severe superior vena cava obstruction syndrome, severe pericardial effusion, acute myocardial ischemia, unstable angina, myocardial infarction within 6 months before screening, or severe arrhythmia such as atrioventricular block of degree Ⅱ or above, or history of NYHA class II or above;
• Respiratory history: history of severe chronic obstructive pulmonary disease, acute exacerbation of chronic obstructive pulmonary disease, severe airway stenosis, throat mass, tracheoesophageal fistula or airway tear, and severe respiratory infection within the last 2 weeks before screening;
• History of nervous and mental system: history of craniocerebral injury, convulsion, intracranial hypertension, cerebral aneurysm, cerebrovascular accident, ischemic stroke or transient ischemic attack (TIA); History of schizophrenia, mania, psychosis, long-term use of psychotropic drugs, cognitive dysfunction, etc. Depression, anxiety, epilepsy history, etc.
• cancer participants with advanced cancer or extensive metastases; 2. Laboratory tests during screening meet any of the following criteria:

(1) Blood routine: white blood cell count < 3.0×109/L; Platelet count < 80×109/L; Hemoglobin < 70 g/L; (2) Coagulation function: prothrombin time (PT) prolongation exceeded the upper limit of normal value for 3 seconds; Activated partial thromboplastin time (APTT) prolonged more than 10 seconds; (3) Liver and kidney function: alanine aminotransferase and/or aspartate aminotransferase > 2×ULN; Total bilirubin > 2×ULN; Serum creatinine > 1.5×ULN; (4) Fasting blood glucose ≥11.1 mmol/L; (5) Participants who did not receive regular antihypertensive treatment or whose blood pressure was poorly controlled (systolic blood pressure ≥160mmHg or ≤90mmHg at screening, and/or diastolic blood pressure ≥100mmHg or ≤60mmHg at screening, excluding abnormalities during anesthesia from admission to PACU and during recovery from anesthesia); (6) QTc >450ms in men and >470ms in women (QTc was calculated with Fridericia's formula); (7) Transcutaneous oxygen saturation (SpO2) <90% during screening (excluding abnormal anesthesia from admission to PACU and anesthesia recovery period); (8) Hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCVAb), syphilis antibody and human immunodeficiency virus (HIV) antibody were positive during the screening period; 3. Medication use

• Patients with a history of severe drug allergy, or other drugs that may be used during the trial, such as anesthetics propofol/sevoflurane, rocuronium, antiemetic drugs, or drugs and their excipients;
• Taking opioid analgesics for any reason for more than 10 consecutive days within 3 months before randomization;
• Drugs that may affect the evaluation of efficacy if the time interval between the last administration of the drug and randomization is less than five half-lives of the drug, including but not limited to the following drugs: Selective α2-adrenoceptor agonists, opioid agonists/antagonists, non-steroidal anti-inflammatory drugs, sedative drugs, monoamine oxidase inhibitors, glucocorticoids, antiepileptic, anxiolytic, antidepressant and other antipsychotic drugs. Refer to the list of banned drugs for specific types.
• Use of a strong inducer or inhibitor of CYP3A within 14 days or 5 half-lives before the first dose of the investigational drug, whichever is longer; 4: Others

(1) Having a history of drug abuse, drug abuse and/or alcohol abuse in the past year, with alcohol abuse defined as drinking an average of > 2 units of alcohol per day (1 unit =360mL of 5% beer or 45mL of 40% liquor or 150mL of wine); (2) Positive results of drug abuse screening during the screening period; (3) Pregnant or lactating women; (4) Had participated in other drug clinical trials (defined as receiving investigational drug or placebo) within 3 months before the screening period; (5) Any sensory dysfunction that may interfere with the ability to assess postoperative pain according to the investigator's judgment; (6) Painful physical conditions that may interfere with postoperative evaluation according to the investigator's judgment; (7) Participants had medical complications during the operation and were not suitable for further study according to the investigator's judgment; (8) Participants with any other factors considered by the investigator to be ineligible for the clinical study.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Китай · 2 центра

• The Third Xiangya Hospital of Central South University, Changsha, hunan — Чанша
• Sichuan Provincial People's Hospital — Чэнду

Идентификаторы

NCT: NCT07491146 · HSK55718-201

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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