Phase I Trial of Emulsified Isoflurane

Phase I Trial of Emulsified Isoflurane in Adult Healthy Volunteers

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.

Study Overview

• Status: Completed
• Conditions: Adverse Effect of Intravenous Anesthetics
• Intervention / Treatment: Drug: Emulsified Isoflurane

• Study Type: Interventional
• Enrollment (Actual): 78
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • Institute of Drug Clinical Trial• GCP Center,West China Hospital, Sichuan University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

16

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Sichuan University
• Investigators: Principal Investigator: Jin Liu, M.D, Department of Anesthesiology, West China Hospital, Sichuan University

Study record dates

Study Major Dates

• Study Start: May 1, 2010
• Primary Completion (Actual): September 1, 2010
• Study Completion (Actual): September 1, 2010

Study Registration Dates

• First Submitted: February 23, 2011
• First Submitted That Met QC Criteria: February 23, 2011
• First Posted (Estimate): February 24, 2011

Study Record Updates

• Last Update Posted (Estimate): February 24, 2011
• Last Update Submitted That Met QC Criteria: February 23, 2011
• Last Verified: February 1, 2010

More Information

Terms related to this study

• Keywords: Phase I trial; Emulsified Isoflurane; Health volunteer
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Central Nervous System Depressants; Anesthetics, General; Anesthetics; Anesthetics, Inhalation; Isoflurane
• Other Study ID Numbers: PITEI; 2009L01628 (Other Identifier: State Food and Drug Administration of P.R. China)