Safety, Pharmacokinetics, and Pharmacodynamics of Continuous KL0011034 Infusion in Healthy Chinese Adults

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.

Inclusion criteria

• 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.

Exclusion criteria

• 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.