A Phase III Investigator Initiated Clinical Trial Evaluating the Efficacy and Safety of CNS7056 (Remimazolam) With a Concomitant Use of Opioid Analgesics in Japanese Patients Undergoing Gastrointestinal Endoscopy

JRCT ID: jRCT2031220129

Registered date:11/06/2022

Basic Information

• Recruitment status: Complete
• Health condition(s) or Problem(s) studied: Japanese patients undergoing gastrointestinal endoscopy in combination with a concomitant use of opi
• Date of first enrollment: 28/06/2022
• Target sample size: 60
• Study type: Interventional

Intervention(s)

After obtaining written consent, eligibility verification will be conducted and, in principle, enrollment will be conducted by the day before the scheduled date of investigational drug administration or endoscopy (if consent is to be obtained on the day of endoscopy, eligibility verification will be performed before the investigational drug administration).

[Prior to the start of endoscopy]
Pethidine hydrochloride or pentazocine as an essential concomitant analgesic will be administered immediately prior to administration of investigational drug in the standard manner of each medical institution (after the start of endoscopic treatment, additional doses may be administered if body movements due to pain stimulation are observed).
Remimazolam, the test drug, (each vial contains 50 mg of remimazolam), is prepared at the time of administration to a concentration of 1 mg/mL and a dose of 3 mg is administered slowly (over at least 15 seconds).
Based on the following criteria, remimazolam will be additionally administered in 1 mg increments if sedation is insufficient (an interval of at least 2 minutes should be required between each additional dose):
- MOAA/S score 3 or less: Start endoscopic therapy.
- MOAA/S score 4 or 5: An additional 1 mg of remimazolam will be administered.
*If sedation is not obtained after 5 additional doses, discontinue the trial.

[After the start of the endoscopy]
Based on the following criteria, if sedation is insufficient, an additional 1 mg of remimazolam will be administered at least 2 minutes interval after the start of the previous dose.
- MOAA/S score 5 or body movement: An additional 1 mg of remimazolam will be administered.

[After the completion of endoscopic treatment]
In case MOAA/S score reaches 5, the patient is evaluated for whether or not the patient can leave the room using the Aldrete Score, and if it is confirmed that the score is 9 or more, the patient is allowed to leave the endoscopy room. Safety confirmation should be performed 24 hours after the endoscopy is completed.

Outcome(s)

Primary Outcome

Success rate of sedation in gastrointestinal endoscopy ("success" is defined when all of the following criteria are satisfied)
1.Sedation (MOAA/S score 3 or less) can be obtained before the start of endoscopy.
2.Successful completion of gastrointestinal endoscopy
3. The number of additional doses does not exceed 5 times per 15 minutes after the start of endoscopy.

Secondary Outcome

-Percentage of subjects who achieved sedation before the start of endoscopy
-Time from initial administration of investigational drug to sedation
-Dose of investigational drug until sedation is obtained (total dose of investigational drug until start of endoscopy)
-Presence or absence of memory during endoscopy
-Total dose and the number of administrations of essential concomitant analgesics
-Time from the end of the endoscopy until the patient is determined to be able to leave the endoscopy room
-Time from the last dose of investigational drug until the patient is determined to be able to leave the endoscopy room

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1. Japanese patients who are scheduled to undergo interventional endoscopy of the upper gastrointestinal tract (oral), large intestine, hepato-biliary-pancreas, or small intestine under the concomitant use of pethidine hydrochloride or pentazocine
2. The age at the time of obtaining consent is 20 years or older
3. BMI is less than 30kg/m2
4. Those whose planned procedure time (from scope insertion to final removal) that is determined by principal investigator or sub-investigator to be longer than 15 minutes
5. Those who can be hospitalized for at least 3 days from the day before the endoscopy to the day after the endoscopy

Exclude criteria

1. Those who regularly use benzodiazepines (due to insomnia, anxiety, spasm, epilepsy, and others) or those who have tolerance to benzodiazepines
2. Those who regularly use analgesics including opioid analgesics (except low-dose aspirin for preventing thrombosis)
3. Those with a history of hypersensitivity to benzodiazepines, opioid analgesics, opioid antagonists (naloxone, levallorphan, and others), or flumazenil, or those with diseases or symptoms that contraindicate the administration of these drugs
4. Alcohol polydipsia (60g or more per day in terms of pure alcohol) or those with complications or a history of alcohol dependence
5. Those with a history of abdominal surgery and who are expected to have difficulty for scope insertion
6. Those with severe respiratory disease or essential hypotension
7. Among the clinical test measurement values within 28 days prior to administration of investigational drug, those that correspond to any of AST, ALT, and total bilirubin values that are 2.5 times or more of the upper limit of standard value (5 times or more in the case of patients undergoing hepato-biliary-pancreatic endoscopy)

Related Information

• Primary Sponsor: Ikehara Hisatomo
• Source(s) of Monetary Support: Mundipharma K.K.