Drug Interactions Trial of Methoxyethyl Etomidate Hydrochloride

A Single-center, Open-label, Single-sequence, Self-crossover Controlled Phase I Clinical Study Evaluating Methoxyethyl Etomidate Hydrochloride Drug Interactions in Healthy Subjects

Sixty-eight healthy subjects were divided into three sequences: A, B and C. The effects of CYP2C19 inhibitor fluconazole and inducer rifampicin on ET-26-HCl injection were evaluated, and the effects of ET-26-HCl injection on pharmacokinetics of omeprazole and midazolam were evaluated.

Study Overview

• Status: Completed
• Conditions: Interaction Drug Food
• Intervention / Treatment: Drug: rifampicin; Drug: ET-26; Drug: Fluconazole; Drug: Omeprazole; Drug: midazolam

• Study Type: Interventional
• Enrollment (Actual): 68
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Shandong
    • Jinan, Shandong, China, 250014
      • The First Affiliated Hospital of Shandong First Medical University (Qianfoshan Hospital of Shandong Province)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. healthy adult male and female subjects aged 18-45 years (inclusive);
2. Body weight: body mass index (BMI) between 18.0 and 30.0 kg/m2 (including the cut-off value), with a body weight of at least 50 kg for male subjects and 45 kg for female subjects;
3. The subjects had good communication with the investigators, signed the informed consent form voluntarily, and were able to complete the trial according to the protocol.

Exclusion Criteria:

-

Auxiliary examination:

1. if the results of physical examination, vital signs, 12-lead electrocardiogram, cortisol test, and laboratory tests are abnormal and clinically meaningful;
2. potentially difficult airway;

3. hepatitis B surface antigen, hepatitis C antibody, HIV antibody or syphilis antibody positive;

   Medication history:

4. use of any drugs that inhibit or induce hepatic drug-metabolizing enzymes within 30 days before screening;
5. use of any prescribed medication within 14 days before dosing;

6. use of over-the-counter drugs, Chinese herbal medicines or food supplements such as vitamins and calcium supplements within 7 days before administration;

   History of disease and surgery:

7. any history of clinically severe illness or any disease or condition that the investigator believes may affect the trial results;
8. patients with a history of adrenal insufficiency, adrenal tumors, or hereditary heme biosynthesis disorders;
9. a history of severe cardiovascular disease, including but not limited to a history of organic heart disease, such as heart failure, myocardial infarction, angina, malignant arrhythmia, such as a history of torssion ventricular tachycardia, ventricular tachycardia, long QT syndrome, or symptoms of long QT syndrome and family history;
10. underwent any surgery within 6 months before screening;

11. allergic constitution; Or who, as judged by the investigator, may be allergic to the trial drug or its excipients;

    Living habits:

12. heavy drinking or regular drinking in the 6 months before screening, i.e. drinking more than 14 units of alcohol per week (1 unit =360 mL of beer or 45 mL of 40% spirits or 150 mL of wine); Or with a positive alcohol breath test at baseline;
13. smoked more than 5 cigarettes per day in the 3 months before screening or could not quit smoking during the study;
14. had a history of drug abuse or drug abuse within 3 months before screening; Or the baseline urine drug test was positive;

15. habitual consumption of grapefruit juice or excessive tea, coffee, and/or caffeinated beverages and inability to quit during the trial;

    Others:

16. those who have difficulty in blood collection, can not tolerate venipuncture or arterial blood collection;
17. participated in any other clinical trial within 3 months before screening;
18. vaccinated within 1 month before screening or planned to be vaccinated during the trial period;
19. pregnant or lactating women;
20. childbearing or sperm donation plan during the trial and half a year after the completion of the trial, or do not agree that the subjects and their spouses should take strict contraceptive measures during the trial and half a year after the completion of the trial;
21. had blood loss or donation >400 mL within 3 months before screening, or received blood transfusion within 1 month;
22. subjects with any factors considered by the investigator to be ineligible for the trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sequence A; rifampicin +ET-26	Drug: rifampicin; rifampicin capsule，600 mg; Drug: ET-26; the dose is 0.8 mg/kg, single dose, Infusion time was 60seconds ± 5seconds
Experimental: Sequence B; Fluconazole+ET-26	Drug: ET-26; the dose is 0.8 mg/kg, single dose, Infusion time was 60seconds ± 5seconds; Drug: Fluconazole; Fluconazole capsules: 400 mg for the first dose and 200 mg for the remaining doses
Experimental: Sequence C; Omeprazole enteric-coated capsules+midazolam+ET-26	Drug: ET-26; the dose is 0.8 mg/kg, single dose, Infusion time was 60seconds ± 5seconds; Drug: Omeprazole; Omeprazole enteric-coated capsules: 20 mg; Drug: midazolam; midazolam injection 0.05 mg/kg was administered intravenously

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic Parameter(ET-26/ etomidate acid)	Cmax	within 1 hour before and 24 hours after the end of ET-26-HCl.from 1 hour before administration of omeprazole enteric-coated capsules until 24 hours after the end of administration.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
modified observer's assessment of alert（MOAA/S） score	The lowest score was 0, indicating full anesthetic sedation, and the highest score was 5, indicating full consciousness.	up to 10 minutes after drug administration.
bispectral index	BIS values range from 0 to 100, with higher values indicating more wakefulness and lower values indicating more severe cortical inhibition.	up to 10 minutes after drug administration.
Eyelash reflex	Gently touching the subject's eyelashes with a cotton swab can cause the subject to blink, that is, there is an eyelash reflex. When the eyelash reflex disappears, the patient has entered a state of anesthesia	up to 2 minutes after drug administration.

Collaborators and Investigators

• Sponsor: Ahon Pharmaceutical Co., Ltd.
• Investigators: Principal Investigator: Wei Zhao, Doctor, The First Affiliated Hospital of Shandong First Medical University (Qianfoshan Hospital of Shandong Province)

Study record dates

Study Major Dates

• Study Start (Actual): December 4, 2023
• Primary Completion (Actual): January 23, 2024
• Study Completion (Actual): January 23, 2024

Study Registration Dates

• First Submitted: January 24, 2025
• First Submitted That Met QC Criteria: February 11, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 12, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Anti-Bacterial Agents; Anti-Infective Agents; Antifungal Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Gastrointestinal Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Enzyme Inhibitors; Nucleic Acid Synthesis Inhibitors; Anesthetics; Central Nervous System Depressants; Neurotransmitter Agents; Adjuvants, Anesthesia; Hypnotics and Sedatives; Anti-Anxiety Agents; Tranquilizing Agents; Psychotropic Drugs; Anesthetics, Intravenous; Anesthetics, General; GABA Modulators; GABA Agents; Steroid Synthesis Inhibitors; Hormone Antagonists; Cytochrome P-450 Enzyme Inhibitors; Antibiotics, Antitubercular; Antitubercular Agents; Leprostatic Agents; Cytochrome P-450 CYP2C9 Inhibitors; Anti-Ulcer Agents; Proton Pump Inhibitors; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP2C8 Inducers; Cytochrome P-450 CYP2C19 Inducers; Cytochrome P-450 CYP2C9 Inducers; Cytochrome P-450 CYP3A Inducers; 14-alpha Demethylase Inhibitors; Cytochrome P-450 CYP2C19 Inhibitors; Midazolam; Omeprazole; Rifampin; Fluconazole
• Other Study ID Numbers: ET-26-HCL-CP-006

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No