Phase I Trial of Emulsified Isoflurane

Study Overview
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Brief Summary
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In this trial, our primary goal is to investigate the safety of intravenous infusion of emulsified isoflurane. In order to protect volunteers, the investigators adopt the modified Fibonacci dose-escalation, starting from a very low dose which is derived from the 1/600 of acute LD50 in pre-clinic study. The trial will be terminated if half of volunteers develop severe adverse event in any dose group or any volunteer develop fatal adverse event in any group.

Official Title
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Phase I Trial of Emulsified Isoflurane in Adult Healthy Volunteers

Conditions
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Adverse Effect of Intravenous Anesthetics

Intervention / Treatment
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* Drug: Emulsified Isoflurane


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 45 years old (50:50 male:female) healthy volunteer; Body Mass Index (BMI) 19 24; health volunteers assessed by medical history and physical examination systolic blood pressure between 100 140mmHg; heart rate between 60 100bpm; pulse oxygen saturation > 97% when inspiring air and reaching 100% after inspiring 100% oxygen for 5 min; with normal result for routine lab test, including complete blood count, chemical test, urine test and stool test; Non-smoker and no history of alcohol or drug abuse; Fully understand the whole process of this trial and sign the informed consent. Exclusion Criteria: Any history of allergy, especially to isoflurane or intralipid; Any suspected history of malignant hyperthermia in the volunteer or his/her relatives; Recent use of a medication with a pronounced effect on the central nervous system or any other organ (within 3 month) Recent participation in other clinical trial (within 1 month) Any history of difficult airway or suspected difficult airway; Pregnancy; Hyperlipidemia.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1 (0.0024 ml/kg)<br>In this group, the volunteers receive emulsified isoflurane (120mg/ml) at the dose of 0.0024ml/kg. | Drug: Emulsified Isoflurane<br> <br> |
| Experimental: Arm 2 (0.006ml/kg)<br>In this group, the volunteers receive emulsified isoflurane (120mg/ml) at the dose of 0.006ml/kg. | Drug: Emulsified Isoflurane<br> <br> |
| Experimental: Arm 3 (0.012ml/kg)<br>In this group, the volunteers receive emulsified isoflurane (120mg/ml) at the dose of 0.012ml/kg. | Drug: Emulsified Isoflurane<br> <br> |
| Experimental: Arm 4 (0.02ml/kg)<br>In this group, the volunteers receive emulsified isoflurane (120mg/ml) at the dose of 0.02ml/kg. | Drug: Emulsified Isoflurane<br> <br> |
| Experimental: Arm 5 (0.0301ml/kg)<br>In this group, the volunteers receive emulsified isoflurane (120mg/ml) at the dose of 0.0301ml/kg. | Drug: Emulsified Isoflurane<br> <br> |
| Experimental: Arm 6 (0.0391ml/kg)<br>In this group, the volunteers receive emulsified isoflurane (120mg/ml) at the dose of 0.0391ml/kg. | Drug: Emulsified Isoflurane<br> <br> |
| Experimental: Arm 7 (0.0508ml/kg)<br>In this group, the volunteers receive emulsified isoflurane (120mg/ml) at the dose of 0.0508ml/kg. | Drug: Emulsified Isoflurane<br> <br> |
| Experimental: Arm 8 (0.066ml/kg)<br>In this group, the volunteers receive emulsified isoflurane (120mg/ml) at the dose of 0.066ml/kg. | Drug: Emulsified Isoflurane<br> <br> |
| Experimental: Arm 9 (0.0859ml/kg)<br>In this group, the volunteers receive emulsified isoflurane (120mg/ml) at the dose of 0.0859ml/kg. | Drug: Emulsified Isoflurane<br> <br> |
| Experimental: Arm 10 (0.1116ml/kg)<br>In this group, the volunteers receive emulsified isoflurane (120mg/ml) at the dose of 0.1116ml/kg. | Drug: Emulsified Isoflurane<br> <br> |
| Experimental: Arm 11 (0.1451ml/kg)<br>In this group, the volunteers receive emulsified isoflurane (120mg/ml) at the dose of 0.1451ml/kg. | Drug: Emulsified Isoflurane<br> <br> |
| Experimental: Arm 12 (0.1886ml/kg)<br>In this group, the volunteers receive emulsified isoflurane (120mg/ml) at the dose of 0.1886ml/kg. | Drug: Emulsified Isoflurane<br> <br> |
| Experimental: Arm 13 (0.2452ml/kg)<br>In this group, the volunteers receive emulsified isoflurane (120mg/ml) at the dose of 0.2452ml/kg. | Drug: Emulsified Isoflurane<br> <br> |
| Experimental: Arm 14 (0.3188ml/kg)<br>In this group, the volunteers receive emulsified isoflurane (120mg/ml) at the dose of 0.3188ml/kg. | Drug: Emulsified Isoflurane<br> <br> |
| Experimental: Arm 15 (0.4144ml/kg)<br>In this group, the volunteers receive emulsified isoflurane (120mg/ml) at the dose of 0.4144ml/kg. | Drug: Emulsified Isoflurane<br> <br> |
| Experimental: Arm 16 (0.5387ml/kg)<br>In this group, the volunteers receive emulsified isoflurane (120mg/ml) at the dose of 0.5387ml/kg. | Drug: Emulsified Isoflurane<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vital Signs | The vital signs include heart rate, cardiac rhythm, blood pressure, respiratory rate, pulse oxygen saturation, body temperature and end-tidal carbon dioxide. All the parameters are measured at the following time points: before drug infusion, recorded as baseline; every one minute, immediately from drug infusion to 15 min after infusion; every two minutes, from 15 min to 30 min after infusion; every five minutes, from 30 min to 60 min afeter infusion; every one hour, from 1 hour to 4 hours after infusion; 8 hours and 24 hours after infusion. | after drug infusion to 24 hours after infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of emulsified isoflurane as an intravenous anesthetics | This secondary outcome is an observational one only. The response to verbal command, to pain stimulus; and eyelash reflex are tested. The orientation and finger-to-nose test are also tested. The end-tidal partial pressure of isoflurane, observer's assessment of alertness/sedation (modified OAS/S score) and Bispectral index (BIS) are also recored. | immediate from drug infusion, up to 24 hours after infusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase I trial, Emulsified Isoflurane, Health volunteer