Sedation depth and safety of intravenous sedation with remimazolam

JRCT ID: jRCTs031220009

Registered date:08/04/2022

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Not applicable (healthy adults)
• Date of first enrollment: 17/05/2022
• Target sample size: 72
• Study type: Interventional

Intervention(s)

Administer remimazolam besylate at the following dosage and administration:
1. Single-dose group
- Group S1: remimazolam 0.05 mg/kg is administered intravenously for 1 min
- Group S2: remimazolam 0.1 mg/kg is administered intravenously for 1 min
- Group S3: remimazolam 0.15 mg/kg is administered intravenously for 1 min
- Group S4: remimazolam 0.2 mg/kg is administered intravenously for 1 min

2. Continuous administration group
- Group C1: remimazolam 0.2 mg/kg/h is administered intravenously for 120 min
- Group C2: remimazolam 0.4 mg/kg/h is administered intravenously for 120 min
- Group C3: remimazolam 0.6 mg/kg/h is administered intravenously for 120 min
- Group C4: remimazolam 0.8 mg/kg/h is administered intravenously for 120 min

3. Single-dose and continuous administration group
- Group SC1: after the intravenous administration of remimazolam 0.08 mg/kg for 1 min, remimazolam 0.2 mg/kg/h is administered intravenously for 120 min
- Group SC2: after the intravenous administration of remimazolam 0.08 mg/kg for 1 min, remimazolam 0.4 mg/kg/h is administered intravenously for 120 min
- Group SC3: after the intravenous administration of remimazolam 0.08 mg/kg for 1 min, remimazolam 0.6 mg/kg/h is administered intravenously for 120 min
- Group SC4: after the intravenous administration of remimazolam 0.08 mg/kg for 1 min, remimazolam 0.8 mg/kg/h is administered intravenously for 120 min
- Maximum single dose: 7 mg

Outcome(s)

• Primary Outcome: Changes in the depth of sedation due to temporal changes in MOAA/S score

Secondary Outcome

1. Subjective and objective findings
2. Temporal changes in BIS value
3. Respiratory endpoints
(1) Temporal changes in SpO2
(2) Temporal changes in EtCO2
(3) Temporal changes in respiratory rate
4. Cardiovascular endpoints
(1) Temporal changes in heart rate
(2) Temporal changes in blood pressure (systolic and diastolic)
(3) Electrocardiogram findings
5. Onset of efficacy
6. Duration of action
7. Rate of change in psychomotor function tests
8. Rate of change in the center of gravity
9. Rate of change in tests of walking ability, dynamic balance, and agility
10. Incidence and degree of adverse event
11. Drug addiction

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: <= 45age old
• Gender: Male

Include criteria

1. Healthy individuals (equivalent to ASA-PS class 1)
2. Sex: male
3. Age: between 18 and 45 years old
4. BMI: 18.5 kg/m2 or more, less than 30 kg/m2
5. Those who voluntarily provided written informed consent upon receiving sufficient explanation and understanding the content of the study

Exclude criteria

1. Those who were deemed ineligible for the study based on the results of clinical examination, physiological examinations, electrocardiogram, pulmonary function test, and health examinations for the confirmation of participant characteristics upon screening
2. Those with more than 2.5 times higher than the upper limit of the facility criteria of the aspartate transaminase and alanine transaminase levels upon screening and total bilirubin level upon screening that was 1.5 times higher than the facility criteria
3. Those treated for severe or poorly controlled (ASA PS class 3 or greater) respiratory diseases (bronchial asthma, etc.), cardiovascular disease (hypertension, etc.), neurological disorders (convulsions, etc.), digestive diseases, liver diseases, kidney disease, hematopoietic diseases, mental illness, endocrine diseases, etc. or with a history of them who were deemed ineligible for the study for security reasons by the principal investigator or sub-investigator
4. Those with a history of oversedation or respiratory depression after the administration of benzodiazepines
5. Those with a history of hypersensitivity to benzo diazepines (study drug components) or flumazenil
6. Those with diseases in which benzodiazepines are contraindicated, such as those with acute angle closure glaucoma and myasthenia gravis, or their symptoms
7. Those with a significantly prolonged corrected QT interval (recurrence of QTc > 450 ms) seen on electrocardiogram
8. Those with Mallampati class 3 or 4
9. Those with high risk of becoming comatosed with respiratory depression due to head injury, bra in tumor, among others
10. Those without the ability to provide informed consent due to complications of dementia, etc.
11. Those with chronic or acute infection
12. Those who used benzodiazepines within 12 months before the administration of the study drug
13. Those who had blood sampling of >400 mL (including blood donation) within 3 months before the administration of the study drug, those who had blood sampling of >200 mL (including blood donation) within 1 month before the administration of the study drug, those who donated blood plasma and platelet components within 2 weeks before the administration of the study drug, or those who received blood transfusion within 3 months before the administration of the study drug
14. Those who received medication within 2 weeks before the administration of the study drug or those who were on medication
15. Those with resting SpO2 of <95% (room air)
16. Those with organic brain abnormalities
17. Smokers (>10 cigarettes / days) and those who did not agree to quit smoking during the study
18. Heavy drinkers (equivalent to 60 g/day of pure alcohol) or those with acute alcohol intoxication and abnormal vital signs
19. Those with complications of drug abuse and dependence and alcohol dependence or a history of them
20. Those who do excessive exercise (1 week before or during the study period) and those undergoing diet for weight control
21. Others who were determined to be ineligible for the study by the principal investigator or sub-investigator

Related Information

• Primary Sponsor: Goto Takashi
• Source(s) of Monetary Support: Japan Society for the Promotion of Science