Clinical Trial of the Effect of Methoxyethyl Etomidate Hydrochloride on the QT Interval of the Heart

A Single-center, Randomized, Open-label, Placebo-controlled Phase I Clinical Trial Was Conducted to Evaluate the Pharmacokinetics and QT Interval Effects of a Single Intravenous Injection of Methoxyethyl Etomidate Hydrochloride in Healthy Subjects

A single intravenous injection of 0.8mg/kg or 2.8mg/kg Et-26-hcl was given to 18 subjects. The effect of plasma concentration on QT interval was evaluated by C-QTc effect model, and the pharmacokinetic characteristics and safety of ET-26 and etomidate acid were evaluated.

Study Overview

• Status: Completed
• Conditions: QT Interval, Variation in
• Intervention / Treatment: Drug: ET-26 0.8mg/kg(low-dose) group; Drug: ET-26 2.8mg/kg(high dose) group

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Shandong
    • Jinan, Shandong, China, 250013
      • Jinan Central Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Healthy adult male and female subjects;
2. Age: 18-45 years old;
3. Body weight: body mass index (BMI) between 19.0 and 28.0 kg/m2, with a body weight of at least 50 kg for male subjects and 45 kg for female subjects;
4. voluntarily sign informed consent;
5. Subjects were able to communicate well with investigators and complete the trial in accordance with the protocol.

Exclusion Criteria:

-

Auxiliary examination:

1. those with clinically significant abnormalities in comprehensive physical examination, vital signs, and laboratory tests (blood routine, blood biochemistry, coagulation function, urine routine, serum cortisol);
2. potentially difficult airway (modified Mallampati score III-IV);
3. abnormal and clinically significant hyperkalemia, hypokalemia, hypermagnesemia, hypomagnesemia, hypercalcemia, or hypocalcemia as judged by the investigator;
4. clinically significant abnormal 12-lead ECG, QTcF≥450 ms, PR interval ≥200 ms, QRS complex duration ≥120ms;

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

   Medication history:

6. use of any drugs that inhibit or induce hepatic drug-metabolizing enzymes within 30 days before screening (see Appendix 1 for details);
7. Use of any known QT-prolonging medication within 30 days before screening (see Appendix 1 for details);
8. use of any prescribed medication within 14 days before dose;

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

   History of disease and surgery:

10. have a history of any clinically serious diseases or diseases or conditions considered by the investigators to be likely to affect the results of the trial, including but not limited to a history of circulatory, respiratory, endocrine, nervous, digestive, urinary, or hematologic, immune, psychiatric, or metabolic diseases;
11. with a history of adrenal insufficiency, adrenal tumors, or hereditary heme biosynthesis disorders;
12. a history of severe cardiovascular disease, including but not limited to organic heart disease, such as heart failure, myocardial infarction, angina pectoris, or malignant arrhythmia, as judged by the investigator; Such as a history of torssion ventricular tachycardia, ventricular tachycardia, long QT syndrome or symptoms of long QT syndrome and family history (as indicated by genetic evidence or sudden death of a close relative at a young age due to cardiac causes);
13. underwent any surgery within 6 months before screening;

14. allergic constitution, such as known allergic history to two or more substances; Or who, as judged by the investigator, may be allergic to the trial drug or its excipients;

    Living habits:

15. 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 during the screening period;
16. used nicotine-containing products between 3 months before screening and study enrollment;
17. with drug abuse or drug abuse history within 3 months before screening; Or the urine drug test was positive in the screening period;

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

    Others:

19. who had difficulty in blood collection or could not tolerate blood collection by venipuncture;
20. participated in any other clinical trial (including drug and device clinical trials) within 3 months before screening;
21. vaccinated within 1 month before screening or planned to be vaccinated during the trial period;
22. pregnant or lactating women;
23. during the trial and within half a year after the completion of the trial, or those who do not agree that the subjects and their spouses should take strict contraceptive measures during the trial and within half a year after the completion of the trial (see Appendix 4 for details);
24. had blood loss or donation > 400 mL within 3 months before screening, or received blood transfusion within 1 month;
25. had any factors considered by the investigator to preclude participation in the trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: low-dose group; Placebo+ET-26 0.8mg/kg	Drug: ET-26 0.8mg/kg(low-dose) group; In a 2:1 ratio, Placebo was administered with normal saline and ET-26 0.8mg/kg for a duration of 60 ±5 seconds.
Other: High dose group; Placebo+ET-26 2.8mg/kg	Drug: ET-26 2.8mg/kg(high dose) group; In a 2:1 ratio, Placebo was administered with normal saline and ET-26 2.8mg/kg for a duration of 60 ±5 seconds.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic parameters	Cmax	from 1 hour before administration of et-26 until 24 hours after the end of administration.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MOAA/S	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
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: Qing Wen, Master, Jinan Central Hospital

Study record dates

Study Major Dates

• Study Start (Actual): November 9, 2023
• Primary Completion (Actual): November 21, 2023
• Study Completion (Actual): November 21, 2023

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

• Other Study ID Numbers: ET-26-HCL-CP-002

Drug and device information, study documents

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