A Study to Evaluate the Safety, Tolerability and Pharmacokinetics of KL0011034 Injection in Healthy Volunteers

Официальное название

A Single-center, Randomized, Double-blind, Placebo-Controlled,Positive-Controlled, Dose-Escalation, Phase 1 Clinical Study to Evaluate the Safety, Tolerability, and Pharmacokinetic Profile of a Single Dose Injection of KL0011034 Injection in Healthy Chinese Volunteers

Обзор

To evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of single intravenous doses of KL0011034 injection in healthy volunteers.

Подробное описание

This trial is a randomized, double-blind, placebo- and active-controlled, single-dose escalation study in healthy volunteers. A total of 76 volunteers will be enrolled. Healthy volunteers will be randomly assigned to receive KL0011034 injection, placebo, or Etomidate Injectable Emulsion. Each volunteer is allowed to participate in only one dose cohort; intra-volunteer dose escalation is not permitted. Enrollment into the next cohort will begin only after safety and tolerability data from the previous cohort have been reviewed and deemed acceptable by the investigator(s) and sponsor. If the highest dose is well tolerated, the investigator(s) and sponsor will evaluate the accumulated data and decide whether to terminate dose escalation or continue to higher dose levels.

Вмешательства

• Препарат KL0011034 injection
  Intravenous injection, single dose
• Препарат Placebo
  Intravenous injection, single dose
• Препарат Etomidate Injectable Emulsion
  Intravenous injection, single dose

Первичные конечные точки

• Number of reported Adverse Events [Срок оценки: From first dose of drug until day 2]

Вторичные конечные точки (9)

• PK parameter Cmax in plasma [Срок оценки: From first dose of drug until day 2]
• PK parameter Tmax in plasma [Срок оценки: From first dose of drug until day 2]
• PK parameter AUC0-t in plasma [Срок оценки: From first dose of drug until day 2]
• PK parameter AUC0-∞ in plasma [Срок оценки: From first dose of drug until day 2]
• PK parameter t1/2 in plasma [Срок оценки: From first dose of drug until day 2]
• Modified Observer's Assessment of Alertness Sedation (MOAA/S) scale [Срок оценки: From first dose of drug until 10 minutes after fully alert on day 1.]
• Electroencephalogram bispectrality index (BIS) monitoring [Срок оценки: From first dose of drug until 10 minutes after fully alert on day 1.]
• Loss of eyelash reflex [Срок оценки: From first dose of drug until the reflex was fully restored on day 1.]
• Modified Aldrete Scoring (Aldrete) Scale [Срок оценки: From being fully alert until meeting the discharge criteria to leave the unit on day 1.]

Критерии участия

Критерии включения

• Able to understand the purpose, content, procedures, and possible risks of the trial,willing to participate and sign the informed consent;
• Volunteers aged 18-45 years (inclusive) at the time of signing the informed consent,no gender limit;
• The body weight: Male ≥ 50.0 kg, Female ≥ 45.0 kg; Body Mass Index (BMI) within the range of 19.0-26.0 kg/m2 (inclusive);
• Agree not to conceive or father a child (and ensure their partners of childbearing potential do not conceive) and agree not to donate gametes from signing informed consent through 3 months after dosing; Agree to use effective contraception during this period;
• Able to communicate well with the investigator, and willing to comply with the protocol restrictions, and cooperate with the completion of the trial process.

Критерии исключения

• The investigator considers that the volunteer has any current or past medical condition (including but not limited to disorders of the central nervous, cardiovascular, endocrine, respiratory, digestive, urinary, hematological, or lymphatic systems) that may interfere with the trial;
• History of anesthesia accident, serious adverse reaction to anesthesia or family history of anesthesia accident prior to screening;
• History of difficult mask ventilation, difficult intubation, or anticipated difficult airway management prior to screening, including but not limited to modified Mallampati score III-IV, bifid or absent uvula, micrognathia, or retrognathia；
• History of asthma, COPD, or obstructive sleep apnea; or current respiratory disease prior to screening;
• History of adrenal insufficiency or adrenal tumor or hereditary heme biosynthesis disorder or hereditary acute porphyria prior to screening;
• Clinically significant abnormalities in physical examination, vital signs, chest X-ray, abdominal ultrasound, or clinical laboratory tests; or abnormal circadian rhythm of cortisol or ACTH deemed clinically significant by the investigator;
• Clinically significant ECG abnormalities at screening, including QTcF≥ 450 ms (men) or ≥ 460 ms (female);
• Seropositive for hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (anti-HCV), HIV antibody (anti-HIV), or Treponema pallidum antibody at screening;
• Pregnancy or lactation at screening; or positive pregnancy test for females of childbearing potential;
• Known history of drug or alcohol abuse or dependence within 12 months prior to screening, or positive urine drug test at screening;
• Alcohol abuse within 6 months prior to screening, positive breath alcohol test at screening, or unwillingness to abstain from alcohol during the trail;
• Positive urine cotinine test at screening, or history of regular smoking (≥5 cigarettes/day) within 6 months prior to screening, or unwillingness to abstain from tobacco use during the trial;
• Habitual consumption of >8 cups/day of tea, coffee, or other caffeinated beverages (1 cup ≈ 250 mL) prior to screening, or unwillingness to abstain from the above beverages during the trial;
• Use of any medications within the past 14 days, including prescription and over-the-counter medications, traditional Chinese medicine, health care products, and vitamins;
• Known allergy to etomidate or other anesthetics；or atopy (defined as allergy to ≥2 medications, foods, or pollen)；or prone to developing rashes or hives； or history of allergic diseases；or known allergy to the excipients or active pharmaceutical ingredients;
• Participation in any clinical trial within 3 months prior to screening, or failure to complete the follow-up period of a previous trial;
• Vaccination within 1 month (inactivated) or 3 months (live) prior to screening, or intent to receive any vaccine dinactivated/live/attenuated vaccine during the trial；
• Blood donation, or blood transfusion, or significant blood loss (>400 ml) within 3 months prior to screening; or planned blood donation or surgery during the trail or within 1 month after the trial;
• Surgery within 3 months prior to screening, ongoing post-surgical recovery, or planned surgical procedure during the trial;
• Difficulty in collecting blood, unable to tolerate venipuncture and/or having a history of haemorrhage or needle halo;
• Volunteers with unprotected sexual intercourse within 2 weeks before administration;
• Poor compliance,or any other circumstance deemed by the investigator to contraindicate participation.

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

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• The Third XIANGYA Hospital of Central South University — Чанша

Идентификаторы

NCT: NCT07474545 · KL0011034-101

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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