A Dose-Finding Study of Amogammadex Sodium for Reversing Vecuronium and Rocuronium-Induced Neuromuscular Blockade

Официальное название

A Multi-Centre, Open-Label, Phase II Study of Amogammadex Sodium as A Reversal Agent for Vecuronium Bromide or Rocuronium Bromide-Induced Moderate (at the Reappearance of T2) and Deep (PTC=1~2) Neuromuscular Blockade in Participants Undergoing ASA Grade 1-2 Elective Surgery

Обзор

Background context: Amogammadex sodium has completed Phase I-III clinical studies in China for reversal of rocuronium-induced blockade. No clinical studies have yet been conducted for vecuronium-induced blockade. Therefore, this dose-finding study in an Australian population is intended to support further Phase III trials in European and American populations for reversal of both rocuronium- and vecuronium-induced neuromuscular blockade. The goal of this clinical trial is to explore how well different doses of amogammadex sodium work to reverse neuromuscular blockade caused by rocuronium or vecuronium during surgery, and to learn about its safety. The main questions it aims to answer are: * How quickly and effectively does amogammadex sodium restore muscle strength after moderate or deep neuromuscular blockade? * What medical problems do participants have when receiving amogammadex sodium? Researchers will compare different doses of amogammadex sodium to see which works best. All participants will receive amogammadex sodium, but at different dose levels depending on when they join the study. Participants will: * Undergo screening up to 28 days before surgery to confirm eligibility * Receive amogammadex sodium at the end of surgery to reverse the effects of the muscle relaxant * Stay in the study for follow-up visits up to 7 days after surgery.

Вмешательства

• Препарат Rocuronium (0.6mg/kg)
  a single-dose intravenous bolus of 0.6 mg/kg rocuronium bromide，additional 0.1-0.2 mg/kg can be provided based on the required depth of neuromuscular blockade for surgery.
• Препарат vecuronium bromide (0.1mg/kg)
  A single-dose intravenous bolus of 0.10 mg/kg vecuronium bromide， additional 0.015 mg/kg can be provided based on the required depth of neuromuscular blockade for surgery.

Первичные конечные точки

• Efficacy Evaluation: The time from the start of the administration of amogammadex sodium to the recovery of the TOFr to 0.9 on day 1. [Срок оценки: Time from the start of the administration of IP to the recovery of the TOFr to 0.9 on day 1]

Вторичные конечные точки (2)

• The Time from the start of administration of amogammadex sodium to recovery of the TOFr to 0.8 on day 1. [Срок оценки: Time from the start of administration of IP to recovery of the TOFr to 0.8 on day 1]
• The Time from the start of administration of amogammadex sodium to recovery of the TOFr to 0.7 on day 1. [Срок оценки: Time from the start of administration of IP to recovery of the TOFr to 0.7 on day 1]

Критерии участия

Критерии включения

• Participants should be willing to participate in the clinical study; the participants should fully understand and know this study and sign an informed consent form; the participants should be willing to follow and be able to complete all study procedures.
• Male or female, 18 ≤ age ≤ 60.
• Participant with the grade of American Society of Anaesthesiologists (ASA) physical status classification 1-2.
• Participants who are scheduled to undergo approximately 2-hour surgery under TIVA with endotracheal intubation, and for whom vecuronium or rocuronium bromide is planned as the sole neuromuscular blocking agent.
• Body mass index (BMI) between 18 and 32 kg/m2 (both exclusive), and weight ≥ 50 kg for males and ≥ 45 kg for females.
• Willingness to use adequate contraception (abstinence is acceptable if it aligns with lifestyle) and refrain from pregnancy, impregnating a partner, or donating sperm/ova from screening until 3 months after study completion. Females of nonchildbearing potential are exempt.

1)For females of childbearing potential: an adequate method of contraception is defined as the use of a condom by the male partner combined with the use of a highly effective method of contraception, either be sexually inactive (abstinent) for 28 days prior to the first dose and throughout the study, or be using one of the following acceptable birth control methods:

• Intrauterine device in place for at least 3 months prior to dosing with a barrier method (condom or diaphragm) and spermicide (if available) throughout the study
• Double barrier methods (e.g., condom and diaphragm) with spermicide (if available) for at least 28 days prior to dosing and throughout the study
• Surgical sterilization of the partner (vasectomy for 6 months minimum) with a barrier method (e.g., condom or diaphragm) and spermicide (if available) throughout the study.
• Bilateral tubal occlusion (e.g. Essure-non-surgical sterility procedure and Bilateral tubal ligation), and/or a vasectomized partner with documented azoospermia 90 days after procedure, if that partner is the sole sexual partner.

2)For males: An adequate method of contraception is defined as use of a condom combined with the use of a highly effective method of contraception by the female partner of childbearing potential. Non-sterilized males with a female partner of childbearing potential must agree to use a double barrier method of birth control until five half-lives plus 90 days after the administration of the study drug.

7.Female participants must be non-pregnant (confirmed by a negative serum at screening and urine pregnancy test on Day -1), non-lactating, or be of nonchildbearing potential (females who have been postmenopausal \[defined as 24 months of amenorrhea in the absence of other biological cause\] or are surgically sterile \[hysterectomy or bilateral oophorectomy or bilateral complete salpingectomy\]).

Критерии исключения

• Known or expected difficult intubation due to anatomical deformities
• Known or suspected neuromuscular diseases, anatomical abnormality or neurological injury history that may affect neuromuscular transmission.
• History or manifestation of disease that, in the opinion of the investigator, renders the participant unsuitable for the study, including but not limited to nervous system, cardiovascular, blood, lymphatic, immune, kidney, liver, gastrointestinal, respiratory, metabolic, and musculoskeletal disorders.
• Participants with abnormal blood pressure not satisfactorily controlled (systolic blood pressure >160 mmHg or < 90 mmHg, diastolic blood pressure > 100 mmHg or < 60 mmHg). For subjects with systolic blood pressure ≥ 140 mmHg and ≤ 160 mmHg or diastolic blood pressure ≥ 90 mmHg and ≤ 100 mmHg and a history of well-controlled blood pressure, and no definite discomfort symptoms, the determination of clinical significance will be made at investigator discretion.
• Known heart failure or other serious cardiovascular diseases with New York Heart Association (NYHA) functional class III or IV; with abnormal ECG, QTcF interval (using Fridericia's formula) male > 450 ms, female > 470 ms, which is judged to have clinical significance by the investigators; with resting heart rate < 60 bpm or > 100 bpm, which is judged to have clinical significance by the investigators.
• History of human immunodeficiency virus (HIV); or positive results at screening for HIV antibody/antigen (HIV Ab/Ag)
• Hepatic insufficiency or known liver disease:

• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2.0 × upper limit of normal (ULN);
• Known liver disease, such as acute hepatitis, chronic hepatitis (HBsAg positive with liver function abnormalities meeting the above criterion a, anti-HCV positive), liver cirrhosis, etc., deemed by the investigator as inappropriate for study inclusion.
• kidney function impairment: Serum creatinine (Cr) >1.5 × ULN or having previously known severe kidney diseases or Estimated Glomerular Filtration Rate (eGFR) (CKD-EPI 2021 formula) < 60 ml/(min·1.73m²) or renal insufficiency.
• Participants who had hereditary haemorrhagic diseases, coagulation disease, or non-traumatic bleeding history (bleeding that requires treatment), and thromboembolism; and currently have a risk of haemorrhage (including coagulation disease, thrombocytopenia \[platelet count < 100×109/L\], thrombin original international standardized ratio > 1.5 or on a routine anticoagulation therapy).
• Participants known or suspected to have malignant hyperthermia or with family history; febrile illness defined as a body temperature above 37.5℃ within 7 days before administration.
• Systemic allergic reactions caused by any known reasons, including food allergy and allergy to animals; participants known or suspected to be allergic to cyclodextrin including sugammadex, anesthetics, muscle relaxants and other drugs used in general anesthesia; participants known to be allergic to gel electrodes.
• Participants who have taken fusidic acid and/or toremifene citrate within 24 hours prior to or scheduled within 24 hours after the study drug administration. Participants receiving drugs known to affect muscle relaxants within 24 hours before or during surgery (e.g., anticonvulsants, aminoglycoside antibiotics, magnesium salts \[Mg2+\]) except for supplements to maintain physiological levels.
• Participants with suspected alcohol or drug abuse;
• Participation in strenuous activity (e.g., heavy lifting, strenuous running, competitive sports such as basketball, football, and singles tennis, mountain climbing, rowing machine training, etc) within 48 hours prior to dosing (Day 1).
• Anatomical deformities on upper extremities that cannot perform monitoring mentioned in the protocol: non-invasive blood pressure monitor, ECG, pulse oximetry, end-tidal capnography and neuromuscular monitoring.
• Participants who participated in other clinical trials within 3 months before the administration.
• Female participants who are pregnant or breastfeeding, who have a positive serum or urine pregnancy test result, or who are unable or unwilling to take contraceptive or abstinence measures approved by the investigator during the study.
• Participants who are considered not suitable for participating in a clinical trial by the investigator or the surgeon.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT07595393 · Aom0498-ACT02-01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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