Clinical Study to Investigate the Efficacy and the Safety of DA-9501 in Sedation During the Surgery With Epidural Anesthesia or Spinal Anesthesia Without Intubation

Study Overview
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Brief Summary
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The purpose of this study is to examine the efficacy and safety of DA-9501 (Dexmedetomidine) in patients who require sedation during the surgery that requires epidural or spinal anesthesia without intubation under monitored sedation care.

Detailed Description
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Phase III, randomized, placebo controlled, double blind, parallel comparative study (Therapeutic confirmatory trial), to evaluate the efficacy and the safety of Dexmedetomidine in non-intubated patients who require sedation during surgery with spinal or epidural anesthesia under monitored sedation care

Official Title
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Phase III Randomized Placebo-controlled Double Blind Comparative Study to Investigate the Efficacy and Safety of DA-9501 in Sedation During the Surgery With Epidural Anesthesia or Spinal Anesthesia Without Intubation Under Monitored Sedation Care

Conditions
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Sedation

Intervention / Treatment
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* Drug: Dexmedetomidine hydrochloride
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient has signed and dated the Informed Consent after the study had been fully explained. Patient is male or female, at least 20 years of age when the Informed Consent is obtained. American Society for Anesthesiologists (ASA) I to III Class. Patient who requires sedation during the elective surgery which requires ≥30mins (expected time) without intubation under monitored sedation care. Patient undergoing a surgery requiring epidural or spinal anesthesia Exclusion Criteria: Patient who underwent general anesthesia within 7 days, or who received other study drugs within 30 days from the date of consent. Patient with <92% SpO2, at the physical examination prior to the study drug administration, or ventilatory failure which requires intubation or Laryngeal Mask. Patient with central nervous system pathology which may lead to increased intracranial pressure, uncontrolled seizures, psychiatric disorder which may be confused with the response to sedation treatment. Patient who require general anesthesia. Patient who receives treatment by alpha-2 agonists or alpha-2 antagonists within seven days of scheduled surgery or procedure. Patient in whom opioids, DA-9501 or other alpha-2 agonists, or drugs which may be used in the study are contraindicated. Patient diagnosed with unstable angina or acute myocardiac infarction within 6 weeks from the date of consent. Patient whose heart rate is <60 bpm, systolic blood pressure is <90 mmHg by the physical examination prior to the study drug administration. Patient has third degree heart block, unless the patient has a pacemaker or transverse pacing wires are in place. Patient who has experienced an increase in alanine transaminase (ALT) and / or aspartate aminotransferase (AST) more than double the upper normal limit within 2 months of the date of consent, or who has a history of liver insufficiency. Pregnant or lactating woman. In the Investigator's or subinvestigator's opinion, the patient has any symptom or condition which might increase risk to the patient by conducting the study or preclude obtaining satisfactory study data

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Dexmedetomidine 0 mcg/kg/hr 10 min Initial dose + Dexmedetomidine 0 mcg/kg/hr Maintenance dose | Drug: Placebo<br> <br> |
| Experimental: Dexmedetomidine 0.067 mcg/kg<br>Dexmedetomidine 0.4 mcg/kg/hr 10 min Initial dose + Dexmedetomidine 0.2 - 0.7 mcg/kg/hr Maintenance dose | Drug: Dexmedetomidine hydrochloride<br>* Dexmedetomidine 0.2 to 0.7 mcg/kg/hr<br>|
| Experimental: Dexmedetomidine 0.25 mcg/kg<br>Dexmedetomidine 1.5 mcg/kg/hr 10 min Initial dose + Dexmedetomidine 0.2 - 0.7 mcg/kg/hr Maintenance dose | Drug: Dexmedetomidine hydrochloride<br>* Dexmedetomidine 0.2 to 0.7 mcg/kg/hr<br>|
| Experimental: Dexmedetomidine 0.5 mcg/kg<br>Dexmedetomidine 3 mcg/kg/hr 10 min Initial dose + Dexmedetomidine 0.2 - 0.7 mcg/kg/hr Maintenance dose | Drug: Dexmedetomidine hydrochloride<br>* Dexmedetomidine 0.2 to 0.7 mcg/kg/hr<br>|
| Experimental: Dexmedetomidine 1.0 mcg/kg<br>Dexmedetomidine 6 mcg/kg/hr 10 min Initial dose + Dexmedetomidine 0.2 - 0.7 mcg/kg/hr Maintenance dose | Drug: Dexmedetomidine hydrochloride<br>* Dexmedetomidine 0.2 to 0.7 mcg/kg/hr<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients Who Did Not Require Rescue Administration of Propofol to Achieve and Maintain Observer's Assessment of Alertness/Sedation (OAA/S) Score ≤4 During the Study Drug Administration. |  | Pre-dose, every 5 ± 2 minutes after start of study drug infusion and every 15 ± 2 minutes until 1 hour after study drug infusion. Before additional administration of sedative. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Propofol Dosing Required to Achieve and Maintain OAA/S Score ≤4 During the Study Drug Administration |  | 15 minutes after the start of study drug, if the OAA/S score is 5. | 
| Dosage of Propofol Dosing Required to Achieve and Maintain OAA/S Score ≤4 During the Study Drug Administration |  | 15 minutes after the start of study drug, if the OAA/S score is 5. | 
| Time to First Rescue Administration of Propofol |  | During the study drug infusion period (≥15 minutes [Approximate]) | 
| Percentage of Patients Who Did Not Require Rescue Administration of Fentanyl During the Study Drug Administration |  | After the surgery start, the administration of fentanyl is permissible as required to treat pain. In case of repeated dose, the dosing interval should be ≥15 minutes. | 
| Number of Fentanyl Dosing Required During the Study Drug Administration. |  | During the study drug administration | 
| Dosage of Fentanyl Dosing Required During the Study Drug Administration. |  | During the study drug administration | 
| Percentage of Time Spent OAA/S Score ≤4 During the Study Drug Infusion |  | Pre-dose, every 5 ± 2 minutes after start of study drug infusion and every 15 ± 2 minutes until 1 hour after study drug infusion. Before additional administration of sedative. | 
| Percentage of Time Spent OAA/S Score 3 to 4 During the Study Drug Infusion |  | Pre-dose, every 5 ± 2 minutes after start of study drug infusion and every 15 ± 2 minutes until 1 hour after study drug infusion. Before additional administration of sedative. | 
| Time to Attain the Point Where Patient is Recovered Assessed by Aldrete Score Following Discontinuation of the Study Drug Infusion |  | Every 15 ± 2 minutes until the score of each item becomes ≥1 and the total value becomes ≥8. | 
| Visual Analogue Scale (VAS) Score Evaluation by Investigator or Sub-investigator (Easiness of Maintenance of Sedation Level) | VAS score ranges from 0 to 10, with 0 being the better/preferred outcome. Low values indicated more ease of maintenance of sedation level. | Within 24 hours after completion of the study drug administration | 
| Visual Analogue Scale (VAS) Score Evaluation by Investigator or Sub-investigator (Stability of Hemodynamic State) | VAS score ranges from 0 to 10, with 0 being the better/preferred outcome. Low values indicated more ease of maintenance of sedation level. | Within 24 hours after completion of the study drug administration | 
| Visual Analogue Scale (VAS) Score Evaluation by Investigator or Sub-investigator (Stability of Respiratory State) | VAS score ranges from 0 to 10, with 0 being the better/preferred outcome. Low values indicated more ease of maintenance of sedation level. | Within 24 hours after completion of the study drug administration | 
| Visual Analogue Scale (VAS) Score Evaluation by Investigator or Sub-investigator (Subject's Cooperation) | VAS score ranges from 0 to 10, with 0 being the better/preferred outcome. Low values indicated more ease of maintenance of sedation level. | Within 24 hours after completion of the study drug administration | 
| Score Evaluation of Satisfaction and Anxiety of the Subject (I Was Satisfied With This Anesthesia Procedure) | Rating: 1 is the better/preferred value for scores from 1 to 4. Low values indicated more ease of maintenance of sedation level. | Within 24 hours after completion of the study drug administration (as much as possible) | 
| Score Evaluation of Satisfaction and Anxiety of the Subject (I Did Not Feel Pain During the Surgery) | Rating: 1 is the better/preferred value for scores from 1 to 4. Low values indicated more ease of maintenance of sedation level. | Within 24 hours after completion of the study drug administration (as much as possible) | 
| Score Evaluation of Satisfaction and Anxiety of the Subject (If You May Undergo a Similar Surgery, the Same Anesthesia Procedure Will be Requested for the Next Time) | Rating: 1 is the better/preferred value for scores from 1 to 4. Low values indicated more ease of maintenance of sedation level. | Within 24 hours after completion of the study drug administration (as much as possible) | 
| Score Evaluation of Satisfaction and Anxiety of the Subject (Assess the Anxiety Level Before Surgery) | Rating: 1 is the better/preferred value for scores from 1 to 5. Low values indicated more ease of maintenance of sedation level. | Within 24 hours after completion of the study drug administration (as much as possible) | 
| Score Evaluation of Satisfaction and Anxiety of the Subject (Assess the Anxiety Level During Surgery) | Rating: 1 is the better/preferred value for scores from 1 to 5. Low values indicated more ease of maintenance of sedation level. | Within 24 hours after completion of the study drug administration (as much as possible) | 
| Score Evaluation of Satisfaction and Anxiety of the Subject (Assess the Anxiety Level After Surgery) | Rating: 1 is the better/preferred value for scores from 1 to 5. Low values indicated more ease of maintenance of sedation level. | Within 24 hours after completion of the study drug administration (as much as possible) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dexmedetomidine, Sedation, Non-intubation, epidural anesthesia, spinal anesthesia