A Single-Center, Randomized, Double-Blind, Active-Controlled Phase 1 Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of Continuous Infusion of KL0011034 Injection in Healthy Chinese Adults
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 30
- 主要终点
- Adverse Events and Serious Adverse Events
研究概览
简要总结
This Phase 1 study will evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of continuous intravenous infusion of KL0011034 Injection in healthy Chinese adults. Approximately 30 participants will be enrolled in three sequential infusion-duration cohorts (1, 2, and 3 hours; 10 participants per cohort). Within each cohort, participants will be randomized in a 4:1 ratio to KL0011034 Injection or active-control propofol for anesthesia maintenance. All participants will receive propofol 2 mg/kg for anesthesia induction. Safety, pharmacokinetic, pharmacodynamic, recovery, and anesthesia-satisfaction assessments will be performed through 24 hours after dosing. Progression to the next infusion-duration cohort will occur only after the preceding cohort is considered safe and tolerable.
详细描述
This is a single-center, randomized, blinded, active-controlled Phase 1 study in 30 healthy Chinese adults. The study contains three sequential cohorts defined by anesthesia-maintenance duration: 1 hour, 2 hours, and 3 hours. Each cohort will enroll approximately 10 participants. Within each cohort, participants will be randomized 4:1 to the investigational-maintenance regimen or the active-control-maintenance regimen.
All participants will receive propofol injectable emulsion 2 mg/kg intravenously over 1 minute (±5 seconds) for anesthesia induction. Maintenance infusion will begin within 30 seconds after induction. Participants assigned to the investigational regimen will receive KL0011034 Injection at a recommended maintenance rate of 1.1 mg/kg/hour; the rate may be adjusted by the investigator to maintain a bispectral index (BIS) of 40 to 60 and must not exceed the protocol-defined upper limit. Participants assigned to the active comparator will receive propofol injectable emulsion at a suggested rate of 4 to 12 mg/kg/hour, adjustable to maintain BIS at 40 to 60.
The 1-hour cohort will be evaluated before the 2-hour cohort begins, and the 2-hour cohort will be evaluated before the 3-hour cohort begins. Progression requires review confirming acceptable safety and tolerability. Participants will undergo safety monitoring, serial plasma sampling for noncompartmental pharmacokinetic analysis, and pharmacodynamic and recovery assessments including MOAA/S, BIS, Modified Aldrete Score, PADSS, recovery quality, and anesthesia satisfaction. The study includes screening, a 1-day baseline period, and approximately 24 hours of post-dose observation.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Participants who fully understand the purpose, content, procedures, and possible risks of the study, voluntarily agree to participate, and sign the informed consent form.
- •Healthy male or female participants aged 18 to 45 years, inclusive, at the time of informed consent.
- •Body weight ≥50.0 kg for males and ≥45.0 kg for females; body mass index 19.0 to 26.0 kg/m², inclusive.
- •From informed consent through 3 months after completion of study-drug infusion, the participant and partner have no reproductive plans and the participant has no sperm or egg donation plans; the participant agrees to use at least one non-pharmacologic contraceptive method through the last pharmacokinetic sample and effective contraception through 3 months after infusion.
- •Able to communicate well with the investigator and willing and able to comply with protocol-specified lifestyle restrictions and complete study procedures.
排除标准
- •Known allergy to etomidate, propofol, or other anesthetic drugs; allergic constitution (for example, allergy to two or more drugs, foods, or pollen); tendency to rash or urticaria; history of allergic disease; or known allergy to the active ingredient or excipients of KL0011034 Injection.
- •History of clinically significant cardiovascular, endocrine, respiratory, gastrointestinal, urinary, neurologic, hematologic, lymphatic, or psychiatric disease that remains clinically significant at screening in the investigator's judgment.
- •History of anesthesia accident, serious anesthesia-related adverse reaction, or family history of anesthesia accident.
- •Difficult ventilation, suspected difficult airway, or anticipated difficult tracheal intubation, including Modified Mallampati Class III-IV, congenital small mouth with macroglossia, mandibular hypoplasia, or similar findings.
- •History of airway disease before or at screening, including bronchial asthma, chronic obstructive pulmonary disease, or sleep apnea syndrome.
- •History of adrenocortical insufficiency, adrenal tumor, hereditary disorder of heme biosynthesis, or hereditary acute porphyria.
- •Clinically significant abnormal findings in physical examination, vital signs, posteroanterior chest radiograph, abdominal ultrasonography, hematology, urinalysis, blood chemistry, coagulation, or infectious-disease screening; or clinically significant abnormal overall circadian pattern of cortisol and/or ACTH at screening in the investigator's judgment.
- •Clinically significant electrocardiogram abnormality at screening, including QTcF ≥450 ms in males or ≥460 ms in females.
- •Pregnant or breastfeeding female, or a woman of childbearing potential with a positive pregnancy test during screening.
- •Unprotected sexual intercourse within 2 weeks before dosing.
- •History of drug abuse or drug dependence within 1 year before screening, or positive urine drug screen at screening.
- •History of alcohol abuse within 6 months before screening, defined as more than 14 standard units per week (1 unit = 360 mL beer, 45 mL of 40% spirits, or 150 mL wine); positive breath alcohol test; or unwillingness to abstain from alcohol and alcohol-containing products during the study.
- •Smoking ≥5 cigarettes per day within 6 months before screening; unwillingness to stop using tobacco products during the study; or positive smoking test at screening.
- •Habitual consumption of more than 8 cups per day (1 cup = 250 mL) of tea, coffee, or caffeine-containing beverages, or unwillingness to abstain from these beverages during the study.
- •Consumption of grapefruit-rich foods or beverages within 48 hours before first dosing.
- •Use of any prescription drug, over-the-counter drug, traditional Chinese medicine, health supplement, or vitamin within 14 days before screening; or use of sedative/analgesic or other anesthetic drugs within 5 days before first dosing.
- •Participation in any clinical trial within 3 months before dosing, or still in the follow-up period of another trial.
- •Receipt of an inactivated vaccine within 1 month before screening or a live/attenuated vaccine within 3 months before screening, or planned vaccination during the study.
- •Blood loss, blood donation, blood transfusion, or receipt of blood products totaling more than 400 mL within 3 months before screening; or planned blood donation or surgery during the study or within 1 month after study completion.
- •Surgery within 3 months before screening, incomplete recovery from surgery, or planned surgery during the study.
- •Special dietary requirements incompatible with standardized meals, swallowing difficulty, habitual anorexia or dieting, or initiation of a markedly abnormal diet (for example, a restrictive or low-sodium diet) within 4 weeks before screening.
- •Difficult venous access, inability to tolerate venipuncture, or history of fainting in response to blood or needles.
- •Expected poor compliance or any other condition that, in the investigator's judgment, makes the participant unsuitable for the study.
研究组 & 干预措施
Cohort 1: KL0011034, 1-Hour Infusion
Participants receive propofol injectable emulsion 2 mg/kg IV for induction, followed by KL0011034 Injection at a recommended maintenance rate of 1.1 mg/kg/hour for 1 hour. The rate may be adjusted to maintain BIS 40-60 within protocol limits.
干预措施: KL0011034 Injection (Drug)
Cohort 2: KL0011034, 2-Hour Infusion
Participants receive propofol injectable emulsion 2 mg/kg IV for induction, followed by KL0011034 Injection at a recommended maintenance rate of 1.1 mg/kg/hour for 2 hours. The rate may be adjusted to maintain BIS 40-60 within protocol limits.
干预措施: KL0011034 Injection (Drug)
Cohort 3: KL0011034, 3-Hour Infusion
Participants receive propofol injectable emulsion 2 mg/kg IV for induction, followed by KL0011034 Injection at a recommended maintenance rate of 1.1 mg/kg/hour for 3 hours. The rate may be adjusted to maintain BIS 40-60 within protocol limits.
干预措施: KL0011034 Injection (Drug)
Cohort 3: Propofol, 3-Hour Infusion
Participants receive propofol injectable emulsion 2 mg/kg IV for induction, followed by propofol injectable emulsion at 4-12 mg/kg/hour for 3 hours. The rate may be adjusted to maintain BIS 40-60.
干预措施: Propofol Injectable Emulsion (Drug)
Cohort 1: Propofol, 1-Hour Infusion
Participants receive propofol injectable emulsion 2 mg/kg IV for induction, followed by propofol injectable emulsion at 4-12 mg/kg/hour for 1 hour. The rate may be adjusted to maintain BIS 40-60.
干预措施: Propofol Injectable Emulsion (Drug)
Cohort 2: Propofol, 2-Hour Infusion
Participants receive propofol injectable emulsion 2 mg/kg IV for induction, followed by propofol injectable emulsion at 4-12 mg/kg/hour for 2 hours. The rate may be adjusted to maintain BIS 40-60.
干预措施: Propofol Injectable Emulsion (Drug)
结局指标
主要结局
Adverse Events and Serious Adverse Events
时间窗: From informed consent through Day 2 discharge/early termination; unresolved adverse events are followed as specified in the protocol.
Incidence, severity, seriousness, relationship, and outcome of adverse events and serious adverse events.
Physical Examination Findings
时间窗: Screening, Day -2 as applicable, Day -1, Day 2/end-of-study, and early termination.
Number of participants with clinically significant changes or abnormalities in physical examination findings.
Holter Monitoring Findings
时间窗: Time-matched baseline on Day -1; Day 1 from infusion start through 24 hours after infusion at protocol-specified time points (infusion start; 30 minutes, 1, 2, 3 hours after start; 2, 10, 30 minutes, 1, 4, 12, 24 hours after completion).
Clinically significant abnormalities detected by protocol-specified Holter monitoring.
Plasma Cortisol Concentration
时间窗: Screening (Day -14 to Day -2) at 07:00-08:00, 16:00 , and 00:00; time-matched baseline on Day -1; on Day 1, pre-dose, at 30 minutes, 1 hour, 2 hours, 3 hours, 4 hours, and 8 hours after infusion start, and at 16:00 and 00:00; and on Day 2 at 08:00.
Plasma cortisol concentration (measured in nmol/L) assessed by protocol-specified laboratory testing.
Plasma Adrenocorticotropic Hormone Concentration
时间窗: Screening (Day -14 to Day -2) at 07:00-08:00, 16:00 , and 00:00; time-matched baseline on Day -1; on Day 1, pre-dose, at 30 minutes, 1 hour, 2 hours, 3 hours, 4 hours, and 8 hours after infusion start, and at 16:00 and 00:00; and on Day 2 at 08:00.
Plasma adrenocorticotropic hormone (ACTH) concentration (measured in pg/mL) assessed by protocol-specified laboratory testing.
Blood Pressure
时间窗: Day 1: pre-dose; during infusion at 30 minutes, 1, 2, 3 hours; post-infusion at 30 minutes, 1, 2, 4, 8, 12, 24 hours; and at early termination.
Change from baseline in blood pressure (systolic and diastolic, measured in mmHg) assessed by standard vital sign measurement.
Pulse Rate
时间窗: Day 1: pre-dose; during infusion at 30 minutes, 1, 2, 3 hours; post-infusion at 30 minutes, 1, 2, 4, 8, 12, 24 hours; and at early termination.
Change from baseline in pulse rate (measured in beats per minute) assessed by standard vital sign measurement.
Respiratory Rate
时间窗: Day 1: pre-dose; during infusion at 30 minutes, 1, 2, 3 hours; post-infusion at 30 minutes, 1, 2, 4, 8, 12, 24 hours; and at early termination.
Change from baseline in respiratory rate (measured in breaths per minute) assessed by standard vital sign measurement.
Body Temperature
时间窗: Day 1: pre-dose; during infusion at 30 minutes, 1, 2, 3 hours; post-infusion at 30 minutes, 1, 2, 4, 8, 12, 24 hours; and at early termination.
Change from baseline in tympanic body temperature (measured in degrees Celsius) assessed by standard vital sign measurement.
Oxygen Saturation (SpO2)
时间窗: Day 1: pre-dose; during infusion at 30 minutes, 1, 2, 3 hours; post-infusion at 30 minutes, 1, 2, 4, 8, 12, 24 hours; and at early termination.
Change from baseline in oxygen saturation (measured as percentage of oxygen saturation) assessed by pulse oximetry.
Heart Rate
时间窗: Pre-dose (within 1 hour before anesthesia induction); after completion of continuous infusion at 30 minutes (±5 minutes), 2 hours (±10 minutes), 4 hours (±10 minutes), 8 hours (±15 minutes), and 24 hours (±20 minutes); and at early termination.
Change from baseline in heart rate (measured in beats per minute) assessed by 12-lead electrocardiogram.
PR Interval
时间窗: Pre-dose (within 1 hour before anesthesia induction); after completion of continuous infusion at 30 minutes (±5 minutes), 2 hours (±10 minutes), 4 hours (±10 minutes), 8 hours (±15 minutes), and 24 hours (±20 minutes); and at early termination.
Change from baseline in PR interval (measured in milliseconds) assessed by 12-lead electrocardiogram.
Change From Time-Matched Baseline in Plasma Cortisol Concentration
时间窗: Screening (Day -14 to Day -2) at 07:00-08:00, 16:00 , and 00:00; time-matched baseline on Day -1; on Day 1, pre-dose, at 30 minutes, 1 hour, 2 hours, 3 hours, 4 hours, and 8 hours after infusion start, and at 16:00 and 00:00; and on Day 2 at 08:00.
Change from time-matched baseline in plasma cortisol concentration (measured in nmol/L) assessed by protocol-specified laboratory testing.
QRS Interval
时间窗: Pre-dose (within 1 hour before anesthesia induction); after completion of continuous infusion at 30 minutes (±5 minutes), 2 hours (±10 minutes), 4 hours (±10 minutes), 8 hours (±15 minutes), and 24 hours (±20 minutes); and at early termination.
Change from baseline in QRS interval (measured in milliseconds) assessed by 12-lead electrocardiogram.
QT Interval
时间窗: Pre-dose (within 1 hour before anesthesia induction); after completion of continuous infusion at 30 minutes (±5 minutes), 2 hours (±10 minutes), 4 hours (±10 minutes), 8 hours (±15 minutes), and 24 hours (±20 minutes); and at early termination.
Change from baseline in QT interval (measured in milliseconds) assessed by 12-lead electrocardiogram.
QTcF Interval
时间窗: Pre-dose (within 1 hour before anesthesia induction); after completion of continuous infusion at 30 minutes (±5 minutes), 2 hours (±10 minutes), 4 hours (±10 minutes), 8 hours (±15 minutes), and 24 hours (±20 minutes); and at early termination.
Change from baseline in QT interval corrected using Fridericia's formula (measured in milliseconds) assessed by 12-lead electrocardiogram.
Change From Time-Matched Baseline in Plasma Adrenocorticotropic Hormone Concentration
时间窗: Screening (Day -14 to Day -2) at 07:00-08:00, 16:00 , and 00:00; time-matched baseline on Day -1; on Day 1, pre-dose, at 30 minutes, 1 hour, 2 hours, 3 hours, 4 hours, and 8 hours after infusion start, and at 16:00 and 00:00; and on Day 2 at 08:00.
Change from time-matched baseline in plasma adrenocorticotropic hormone (ACTH) concentration (measured in pg/mL) assessed by protocol-specified laboratory testing.
次要结局
- Maximum Plasma Concentration (Cmax) of KL0011034(pre-induction and pre-maintenance; during infusion at 5, 10, 20, 30, and 45 minutes and 1, 2, or 3 hours as applicable; after infusion at 2, 5, 10, 20, 30, and 40 minutes and 1, 2, 4, 8, 12, and 24 hours.)
- Time to Maximum Plasma Concentration (Tmax) of KL0011034(Pre-induction and pre-maintenance; during infusion at 5, 10, 20, 30, and 45 minutes and 1, 2, or 3 hours as applicable; after infusion at 2, 5, 10, 20, 30, and 40 minutes and 1, 2, 4, 8, 12, and 24 hours.)
- Area Under the Curve From Time Zero to the Last Quantifiable Concentration (AUC0-t) of KL0011034(Pre-induction and pre-maintenance; during infusion at 5, 10, 20, 30, and 45 minutes and 1, 2, or 3 hours as applicable; after infusion at 2, 5, 10, 20, 30, and 40 minutes and 1, 2, 4, 8, 12, and 24 hours.)
- Area Under the Curve From Time Zero Extrapolated to Infinity (AUC0-∞) of KL0011034(Pre-induction and pre-maintenance; during infusion at 5, 10, 20, 30, and 45 minutes and 1, 2, or 3 hours as applicable; after infusion at 2, 5, 10, 20, 30, and 40 minutes and 1, 2, 4, 8, 12, and 24 hours.)
- Area Under the Curve From Time Zero to 24 Hours (AUC0-24h) of KL0011034(Pre-induction and pre-maintenance; during infusion at 5, 10, 20, 30, and 45 minutes and 1, 2, or 3 hours as applicable; after infusion at 2, 5, 10, 20, 30, and 40 minutes and 1, 2, 4, 8, 12, and 24 hours.)
- Percentage of AUC Extrapolated to Infinity (AUC%Extrap) of KL0011034(Pre-induction and pre-maintenance; during infusion at 5, 10, 20, 30, and 45 minutes and 1, 2, or 3 hours as applicable; after infusion at 2, 5, 10, 20, 30, and 40 minutes and 1, 2, 4, 8, 12, and 24 hours.)
- Clearance (CL) of KL0011034(Pre-induction and pre-maintenance; during infusion at 5, 10, 20, 30, and 45 minutes and 1, 2, or 3 hours as applicable; after infusion at 2, 5, 10, 20, 30, and 40 minutes and 1, 2, 4, 8, 12, and 24 hours.)
- Volume of Distribution (Vd) of KL0011034(Pre-induction and pre-maintenance; during infusion at 5, 10, 20, 30, and 45 minutes and 1, 2, or 3 hours as applicable; after infusion at 2, 5, 10, 20, 30, and 40 minutes and 1, 2, 4, 8, 12, and 24 hours.)
- Terminal Elimination Rate Constant (λz) of KL0011034(Pre-induction and pre-maintenance; during infusion at 5, 10, 20, 30, and 45 minutes and 1, 2, or 3 hours as applicable; after infusion at 2, 5, 10, 20, 30, and 40 minutes and 1, 2, 4, 8, 12, and 24 hours.)
- Terminal Elimination Half-Life (t1/2) of KL0011034(Pre-induction and pre-maintenance; during infusion at 5, 10, 20, 30, and 45 minutes and 1, 2, or 3 hours as applicable; after infusion at 2, 5, 10, 20, 30, and 40 minutes and 1, 2, 4, 8, 12, and 24 hours.)
- Mean Residence Time From Time Zero to Infinity (MRT0-∞) of KL0011034(Pre-induction and pre-maintenance; during infusion at 5, 10, 20, 30, and 45 minutes and 1, 2, or 3 hours as applicable; after infusion at 2, 5, 10, 20, 30, and 40 minutes and 1, 2, 4, 8, 12, and 24 hours.)
- Maximum Plasma Concentration (Cmax) of KL0011034 Metabolite A644S(A)-Z7(Pre-induction and pre-maintenance; during infusion at 5, 10, 20, 30, and 45 minutes and 1, 2, or 3 hours as applicable; after infusion at 2, 5, 10, 20, 30, and 40 minutes and 1, 2, 4, 8, 12, and 24 hours.)
- Time to Maximum Plasma Concentration (Tmax) of KL0011034 Metabolite A644S(A)-Z7(Pre-induction and pre-maintenance; during infusion at 5, 10, 20, 30, and 45 minutes and 1, 2, or 3 hours as applicable; after infusion at 2, 5, 10, 20, 30, and 40 minutes and 1, 2, 4, 8, 12, and 24 hours.)
- Area Under the Curve From Time Zero to the Last Quantifiable Concentration (AUC0-t) of KL0011034 Metabolite A644S(A)-Z7(Pre-induction and pre-maintenance; during infusion at 5, 10, 20, 30, and 45 minutes and 1, 2, or 3 hours as applicable; after infusion at 2, 5, 10, 20, 30, and 40 minutes and 1, 2, 4, 8, 12, and 24 hours.)
- Area Under the Curve From Time Zero Extrapolated to Infinity (AUC0-∞) of KL0011034 Metabolite A644S(A)-Z7(Pre-induction and pre-maintenance; during infusion at 5, 10, 20, 30, and 45 minutes and 1, 2, or 3 hours as applicable; after infusion at 2, 5, 10, 20, 30, and 40 minutes and 1, 2, 4, 8, 12, and 24 hours.)
- Area Under the Curve From Time Zero to 24 Hours (AUC0-24h) of KL0011034 Metabolite A644S(A)-Z7(Pre-induction and pre-maintenance; during infusion at 5, 10, 20, 30, and 45 minutes and 1, 2, or 3 hours as applicable; after infusion at 2, 5, 10, 20, 30, and 40 minutes and 1, 2, 4, 8, 12, and 24 hours.)
- Percentage of AUC Extrapolated to Infinity (AUC%Extrap) of KL0011034 Metabolite A644S(A)-Z7(Pre-induction and pre-maintenance; during infusion at 5, 10, 20, 30, and 45 minutes and 1, 2, or 3 hours as applicable; after infusion at 2, 5, 10, 20, 30, and 40 minutes and 1, 2, 4, 8, 12, and 24 hours.)
- Clearance (CL) of KL0011034 Metabolite A644S(A)-Z7(Pre-induction and pre-maintenance; during infusion at 5, 10, 20, 30, and 45 minutes and 1, 2, or 3 hours as applicable; after infusion at 2, 5, 10, 20, 30, and 40 minutes and 1, 2, 4, 8, 12, and 24 hours.)
- Volume of Distribution (Vd) of KL0011034 Metabolite A644S(A)-Z7(Pre-induction and pre-maintenance; during infusion at 5, 10, 20, 30, and 45 minutes and 1, 2, or 3 hours as applicable; after infusion at 2, 5, 10, 20, 30, and 40 minutes and 1, 2, 4, 8, 12, and 24 hours.)
- Terminal Elimination Rate Constant (λz) of KL0011034 Metabolite A644S(A)-Z7(Pre-induction and pre-maintenance; during infusion at 5, 10, 20, 30, and 45 minutes and 1, 2, or 3 hours as applicable; after infusion at 2, 5, 10, 20, 30, and 40 minutes and 1, 2, 4, 8, 12, and 24 hours.)
- Terminal Elimination Half-Life (t1/2) of KL0011034 Metabolite A644S(A)-Z7(Pre-induction and pre-maintenance; during infusion at 5, 10, 20, 30, and 45 minutes and 1, 2, or 3 hours as applicable; after infusion at 2, 5, 10, 20, 30, and 40 minutes and 1, 2, 4, 8, 12, and 24 hours.)
- Mean Residence Time From Time Zero to Infinity (MRT0-∞) of KL0011034 Metabolite A644S(A)-Z7(Pre-induction and pre-maintenance; during infusion at 5, 10, 20, 30, and 45 minutes and 1, 2, or 3 hours as applicable; after infusion at 2, 5, 10, 20, 30, and 40 minutes and 1, 2, 4, 8, 12, and 24 hours.)
- Maximum Plasma Concentration (Cmax) of Propofol(Pre-induction and pre-maintenance; during infusion at 5, 10, 20, 30, and 45 minutes and 1, 2, or 3 hours as applicable; after infusion at 2, 5, 10, 20, 30, and 40 minutes and 1, 2, 4, 8, 12, and 24 hours.)
- Time to Maximum Plasma Concentration (Tmax) of Propofol(Pre-induction and pre-maintenance; during infusion at 5, 10, 20, 30, and 45 minutes and 1, 2, or 3 hours as applicable; after infusion at 2, 5, 10, 20, 30, and 40 minutes and 1, 2, 4, 8, 12, and 24 hours.)
- Area Under the Curve From Time Zero to the Last Quantifiable Concentration (AUC0-t) of Propofol(Pre-induction and pre-maintenance; during infusion at 5, 10, 20, 30, and 45 minutes and 1, 2, or 3 hours as applicable; after infusion at 2, 5, 10, 20, 30, and 40 minutes and 1, 2, 4, 8, 12, and 24 hours.)
- Area Under the Curve From Time Zero Extrapolated to Infinity (AUC0-∞) of Propofol(Pre-induction and pre-maintenance; during infusion at 5, 10, 20, 30, and 45 minutes and 1, 2, or 3 hours as applicable; after infusion at 2, 5, 10, 20, 30, and 40 minutes and 1, 2, 4, 8, 12, and 24 hours.)
- Area Under the Curve From Time Zero to 24 Hours (AUC0-24h) of Propofol(Pre-induction and pre-maintenance; during infusion at 5, 10, 20, 30, and 45 minutes and 1, 2, or 3 hours as applicable; after infusion at 2, 5, 10, 20, 30, and 40 minutes and 1, 2, 4, 8, 12, and 24 hours.)
- Percentage of AUC Extrapolated to Infinity (AUC%Extrap) of Propofol(Pre-induction and pre-maintenance; during infusion at 5, 10, 20, 30, and 45 minutes and 1, 2, or 3 hours as applicable; after infusion at 2, 5, 10, 20, 30, and 40 minutes and 1, 2, 4, 8, 12, and 24 hours.)
- Clearance (CL) of Propofol(Pre-induction and pre-maintenance; during infusion at 5, 10, 20, 30, and 45 minutes and 1, 2, or 3 hours as applicable; after infusion at 2, 5, 10, 20, 30, and 40 minutes and 1, 2, 4, 8, 12, and 24 hours.)
- Volume of Distribution (Vd) of Propofol(Pre-induction and pre-maintenance; during infusion at 5, 10, 20, 30, and 45 minutes and 1, 2, or 3 hours as applicable; after infusion at 2, 5, 10, 20, 30, and 40 minutes and 1, 2, 4, 8, 12, and 24 hours.)
- Terminal Elimination Rate Constant (λz) of Propofol(Pre-induction and pre-maintenance; during infusion at 5, 10, 20, 30, and 45 minutes and 1, 2, or 3 hours as applicable; after infusion at 2, 5, 10, 20, 30, and 40 minutes and 1, 2, 4, 8, 12, and 24 hours.)
- Terminal Elimination Half-Life (t1/2) of Propofol(Pre-induction and pre-maintenance; during infusion at 5, 10, 20, 30, and 45 minutes and 1, 2, or 3 hours as applicable; after infusion at 2, 5, 10, 20, 30, and 40 minutes and 1, 2, 4, 8, 12, and 24 hours.)
- Mean Residence Time From Time Zero to Infinity (MRT0-∞) of Propofol(Pre-induction and pre-maintenance; during infusion at 5, 10, 20, 30, and 45 minutes and 1, 2, or 3 hours as applicable; after infusion at 2, 5, 10, 20, 30, and 40 minutes and 1, 2, 4, 8, 12, and 24 hours.)
- Sedation/Anesthesia Success Rate(Day 1, from start of anesthesia induction until MOAA/S ≤1, assessed up to 24 hours after the start of infusion.)
- Duration With Bispectral Index ≤60(Day 1, continuously from pre-induction until 10 minutes after full recovery.)
- Total Duration With Bispectral Index 40 to 60(Day 1, continuously from pre-induction until 10 minutes after full recovery.)
- Time to MOAA/S Score ≤1(Day 1, from start of anesthesia induction until the first MOAA/S score ≤1, assessed every 20 seconds after induction up to 24 hours after the start of infusion.)
- Total Duration With MOAA/S Score ≤1(Day 1, from induction through recovery assessments, assessed up to 24 hours after the start of infusion.)
- MOAA/S Sedation Score(Day 1: pre-induction; every 20 seconds after induction until MOAA/S ≤1 (assessed up to 24 hours); at 5, 10, 15, 20, 30, 45 minutes and 1, 2, 3 hours after infusion start; and every 2 minutes after infusion end until 10 minutes after full recovery.)
- Modified Aldrete Score(Day 1, every 2 minutes after full recovery until three consecutive scores ≥9, assessed up to 24 hours after the start of infusion.)
- Post-Anesthetic Discharge Scoring System Score(Day 1, every 5 minutes after three consecutive Aldrete scores ≥9 until three consecutive PADSS scores ≥9, assessed up to 24 hours after the start of infusion.)
- Time to Full Recovery(Day 1, from end of infusion until full recovery, assessed up to 24 hours after the start of infusion.)
- Time to Recovery-Area Discharge Readiness(Day 1, from full recovery until recovery-area discharge criteria are met, assessed up to 24 hours after the start of infusion.)
- Time to Hospital Discharge Readiness(Day 1, from recovery-area discharge readiness until hospital discharge criteria are met, assessed up to 24 hours after the start of infusion.)
- Mini-Mental State Examination Score(Day -1, and within 30 minutes, 1 hour, 2 hours, and 4 hours after discharge readiness; later assessments may stop once the result is normal.)
- Finger-to-Nose Test Result(Day -1, and within 30 minutes, 1 hour, 2 hours, and 4 hours after discharge readiness; later assessments may stop once the result is normal.)
- Anesthesiologist Satisfaction(30 minutes (±10 minutes) after full recovery on Day 1.)
- Injection Site Reactions(Day 1: pre-dose; 10 seconds after induction; at infusion start; 1, 2, 3 hours after start; 10 minutes after full recovery; before Day 2 discharge; and at early termination (within 6 hours after infusion end).)
研究者
Guoping Yang
Professor of Clinical Pharmacology
The Third Xiangya Hospital of Central South University