Japan Phase 2/3 Clinical Study With BLM-240 (Desflurane)

Study Overview
=================
Brief Summary
-----------------
The purposes of this study are to evaluate the efficacy and safety of desflurane (BLM-240) as an anesthetic agent and to demonstrate the non-inferiority of desflurane to sevoflurane in term of awakening/recovery from anesthesia.

Detailed Description
-----------------
The study evaluates the efficacy and safety of the use of desflurane (BLM-240) (with and without nitrous oxide) in maintenance of general anesthesia in adult patients undergoing surgical procedures typically performed under general anesthesia in Japan (thoracic, abdominal, joints, back, and neck), where analgesics and muscle relaxants are concomitantly used. The study is also intended to demonstrate the non-inferiority of desflurane with nitrous oxide to sevoflurane with nitrous oxide in time to awakening/recovery.

Official Title
-----------------
Phase 2/3 Clinical Study With BLM-240 in Adult Surgery Patients That Need General Anesthesia

Conditions
-----------------
Anesthesia

Intervention / Treatment
-----------------
* Drug: desflurane
* Drug: desflurane/nitrous oxide
* Drug: sevoflurane/nitrous oxide


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: ASA PS 1-3 age: older than 19 y and younger than 70 y undergoing surgery of the thorax(thoracotomy, thoracotomy plus laparotomy, endoscopy; but excluding cardiovascular),abdomen(laparotomy,endoscopy;but excluding cesarean section), joints (including peripheral vessels), back (spine)or neck (neck, throat) willing to be hospitalized for at least 3 days and 2 nights (from the day before surgery to the day after surgery) having given written consent Exclusion Criteria: need for spinal subarachnoid, epidural or local anesthesia (except local surface or infiltration anesthesia for catheter insertion or use of local anesthetic for testing before inserting epidural catheter for post-surgical pain) contraindication for use of nitrous during surgery anticipated need for postoperative transfer to intensive care unit and receive mechanical pulmonary ventilation BMI of 30 kg/m2 or more serious hepatic, renal, or circulatory disorder (Grade 3 per Notification 80 by MHW, Pharmaceutical Affairs Bureau, Safety Division) uncontrollable hypertension (SBP 160 mmHg or higher while on antihypertensive therapy) emergency surgery history of hypersensitivity to components of sevoflurane, fentanyl, propofol, vecuronium or other anesthetic contraindication to sevoflurane, fentanyl, propofol, or vecuronium exposure or suspected exposure to inhalational halogenated anesthetic within 3 mo prior to consent known or suspected history or family history of malignant hyperthermia considered likely to have difficulty in receiving tracheal intubation due to conditions such as brachygnathia, micrognathia, bucked teeth, articular rheumatism or injury of cervical spine/cervical cord known or suspected to be pregnant or lactating participated in a clinical study within 6 mo prior to consent history of drug dependence history of epilepsy otherwise judged by the investigator to be unsuitable for the study

Ages Eligible for Study
-----------------
Minimum Age: 20 Years
Maximum Age: 69 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: desflurane<br> | Drug: desflurane<br>* volatile liquid for inhalation<br>* Other names: BLM-240;|
| Experimental: desflurane/N2O<br> | Drug: desflurane/nitrous oxide<br>* volatile liquid for inhalation with gas for inhalation<br>* Other names: N2O;|
| Active Comparator: sevoflurane/N2O<br> | Drug: sevoflurane/nitrous oxide<br>* volatile liquid for inhalation and gas for inhalation<br>* Other names: N2O;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Body Movement During Anesthetic Maintenance | The investigator or sub-investigator observed the patient for body movement (excluding bucking) during anesthetic maintenance. | Day 1 (During surgery, duration ranging <2 hours, 2-4 hours, and ≥4 hours) | 
| Number of Participants With Recall/Memory Issues During Anesthetic Maintenance | The investigator or sub-investigator observed the patient for the presence or absence of awakening during anesthetic maintenance and interviewed the patient on the day after surgery to confirm whether the patient has any memory during anesthetic maintenance. | Day 1 (During surgery, duration ranging <2 hours, 2-4 hours, and ≥4 hours) | 
| Number of Participants Requiring Rescue Treatment During Anesthetic Maintenance | Rescue medication includes vasopressors and depressors. | Day 1 (During surgery, duration ranging <2 hours, 2-4 hours, and ≥4 hours) | 
| Number of Participants Not Receiving Rescue Treatment Whose Blood Pressure/Heart Rate Maintained Above/Below 70% | Rescue medication includes vasopressors and depressors. Percentage of observation points at which systolic pressure 80 to <150 mmHg and heart rate 50 to <100 bpm could be maintained  | Day 1 (During surgery, duration ranging <2 hours, 2-4 hours, and ≥4 hours) | 
| Number of Participants Receiving Rescue Treatment Whose Blood Pressure/Heart Rate Maintained Above/Below 70% | Rescue medication includes vasopressors and depressors. Percentage of observation points at which no rescue treatment was judged to be required based on blood pressure/heart rate | Day 1 (During surgery, duration ranging <2 hours, 2-4 hours, and ≥4 hours) | 
| Overall Assessment of Efficacy | Evaluation on the efficacy (ability) of BLM-240 as an anesthetic drug. | Day 1 (During surgery, duration ranging <2 hours, 2-4 hours, and ≥4 hours) | 
| Time to Extubation | Evaluation of Awakening/Recovery from Anesthesia from end of study drug inhalation to extubation. The patient was extubated when the following signs were observed:(1) clear consciousness, (2) ability to breathe spontaneously (minute ventilation >=50 mL/kg/min), and (3) stable circulatory dynamics (systolic pressure: >=100 mmHg). | Day 1 (Post-Surgery, from end of study drug inhalation to extubation) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Awakening | Time from the end of study drug inhalation. After the end of inhalation of the study drug, the investigator commanded the patient to open his/her eyes once every minute to check whether he/she awoke and recorded the time of awakening. | Day 1 (Post-Surgery, from the end of study drug inhalation to awakening) | 
| Time to Stating Birth Date | After extubation, the investigator called and asked the patient to state the birth date once every minute and recorded the time the patient could state the birth date. Time from the end of study drug inhalation. | Day 1 (Post-Surgery, after extubation) | 
| Time to Reaching an Aldrete Score >=8 (Min) | Score includes a ranking of 0-2 (higher shows improvement) in activity, respiration, circulation, consciousness, and O2 saturation (SpO2). After extubation, the investigator observed the patient's condition every 5 minutes until the Aldrete score reached >=8 and recorded the Aldrete scores at 5-minute intervals. | Day 1 (Post-Surgery, after extubation) | 
| Time to Clear Consciousness | Clear consciousness means that patients responded to investigator's command for physical movement such as hold my finger tight. | Day 1 (Post-Surgery, from awakening to before extubation) | 
| Changes in Bispectral Index (BIS) Over Time During Anethetic Maintenance | BIS is used to monitor depth of anesthesia. The BIS monitor provides a single number, which ranges from 0 (equivalent to EEG silence) to 100. A BIS value between 40 and 60 generally indicates an appropriate level for general anesthesia. | Day 1 (During surgery, duration ranging <2 hours, 2-4 hours, and ≥4 hours) | 
| Number of Participants Requiring Rescue Medication Due to Rise in Blood Pressure or Heart Rate | Rescue medication can include vasopressors and depressors. | Day 1 (During surgery, duration ranging <2 hours, 2-4 hours, and ≥4 hours) | 
| Number of Participants Requiring Rescue Medication Due to Drop in Blood Pressure or Heart Rate | Rescue medication can include vasopressors and depressors. | Day 1 (During surgery, duration ranging <2 hours, 2-4 hours, and ≥4 hours) | 
| Number of Participants Requiring Rescue Medication Due to Arrhythmia | Rescue medication can include vasopressors and depressors. | Day 1 (During surgery, duration ranging <2 hours, 2-4 hours, and ≥4 hours) | 
| Range of End-Tidal Anesthetic Percent Concentrations During Anesthetic Maintenance | Measurement by infrared absorption spectrometry. The concentrations of BLM-240 and sevoflurane at the start of inhalation were set at 3% and 1%,respectively (by vaporizer dial setting). Concentrations are monitored to determine which levels keep the patient in stable condition without requiring rescue treatment. | Day 1 [just before the start of inhalation of study drug, during anesthetic maintenance (every 5 minutes after the start of inhalation of study drug), at the end of inhalation of study drug, immediately after awakening, and just before extubation] | 
| Range of Inspired Anesthetic Concentrations Below End-Tidal Anesthetic Percent Concentrations During Anesthetic Maintenance | Measurement by infrared absorption spectrometry. Ranges reflecting when concentrations were stable. The inspired concentration was adjusted depending on the patient's condition during anesthetic maintenance (gas flow rate: 2 to 6 L/min). | Day 1 [just before the start of inhalation of study drug, during anesthetic maintenance (every 5 minutes after the start of inhalation of study drug), at the end of inhalation of study drug, and just before extubation] | 
| End-Tidal Anesthetic Percent Concentrations Successfully Maintained Anesthesia | Successfully maintaining anesthesia is defined as keeping the patient in stable condition (systolic pressure 80 to <150 mmHg and heart rate 50 to <100bpm) without requiring rescue treatment or additional dose of opioid analgesics (<=2 ug/kg/hr).If patient was found to have body movement, recall, or memory during anesthetic maintenance, data for such patient were to be excluded from summary statistic calculation. | Day 1 [just before the start of inhalation of study drug, during anesthetic maintenance (every 5 minutes after the start of inhalation of study drug), at the end of inhalation of study drug, immediately after awakening, and just before extubation] | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
anesthesia, desflurane