Synopsis Trial Number 12.4.104 Trial Title First administration to man of Org 25435 a new intravenous anesthetic Trial Center Phase 1 Clinical Trials Unit Limited, 119 Looseleigh Lane, Derriford, Plymouth PL6 5HH Publication Studied Period The first subject was screened on 04/01/2000 and the final subject completed the follow up on 24/03/2000.~Phase of Development Phase I (First into Man) Objectives To assess the safety, tolerability and efficacy of Org 25435 as an intravenous anesthetic and to obtain preliminary pharmacodynamic and pharmacokinetic details of Org 25435.~Methodology Sequential rising dose study of an intravenous anesthetic in young healthy males, at up to eight dose levels.~Number of Subjects 19 healthy male volunteers were included into the dose escalation part of the study and an additional 7 volunteers participated in the Target Controlled Infusion (TCI) part of the study.~Diagnosis and Main Criteria for Inclusion Inclusion criteria:~Good physical and mental health: absence of a clinically relevant medical history; Clinically acceptable hematology and clinical chemistry results; Hemoglobin > 13.5 g/dl; Normal ECG; Diastolic blood pressure 60 to 90 mmHg inclusive; Normal cardiac morphology demonstrated by echocardiography; Satisfactory cardiovascular response to exercise, measured by the Bruce Protocol, subjects must have completed Bruce stage 5; Aged 18 to 35 years inclusive; Body mass index (BMI) 19 to 27 inclusive, weight 65 to 100 kg inclusive; Negative hepatitis screen; Non-smoker for at least 6 months; Previous experience of general anesthesia with no problems reported; Willingness to give written informed consent; Ability to communicate well with the Investigators.~Investigational Product Dose Mode of Administration Batch Number 1 vial 200mg Org 25435 / 10ml solvent for reconstitution Intended doses: 0.25, 0.5, 1.0, 2.0, 3.0, 4.0, 5.0 and 6.0 mg/kg Intravenous 9J521 Duration of Treatment~Dose Escalation phase:~Each study treatment consisted of an intravenous infusion of Org 25435, given by Infusion pump over exactly 1 minute.~Target Controlled Infusion phase:~Each study treatment consisted of an intravenous infusion of Org25435 given by a computer-controlled infusion over 30 minutes.~Criteria for Evaluation Tolerability, adverse events, EEG effects, cardiovascular effects, electrocardiogram (ECG), excitatory phenomena, respiratory effects, laboratory safety blood analyses, pharmacodynamic and pharmacokinetic measurements. Efficacy Induction phenomena; time of cessation of speech, eye closure, loss of eyelash reflex, eyes open on command, limb movement on command and syringe drop. Other Induction phenomena; pain on injection, sign of histamine release, excitatory phenomena, respiratory depression, apnea. Recovery phenomena; nausea / vomiting, delirium, shivering, disturbed psychomotor function, eye opening on command, spontaneous respiration, adequate respiration, move limbs on command, increased saliva production.~Statistical Methods Formal statistical methods are not appropriate in this small pilot investigative study where group sizes comprise 5 or less subjects. All data collected is presented and summarized according to investigation type (Dose Escalation or TCI).
Title: First administration to man of Org 25435, a new intravenous anaesthetic.~Protocol: 12.4.104~Clinical Phase: Phase I~Study Site:~Phase I Clinical Trials Unit Ltd Old Convent of Notre Dame 119 Looseleigh Lane Plymouth PL6 5HH United Kingdom~Objectives: To assess the safety, tolerability, preliminary pharmacokinetics and efficacy of Org 25435 as an intravenous anaesthetic.~Study Design: Sequential study of an intravenous anaesthetic in young healthy males, at up to eight dose levels.~Study Drug: Org 25435, a water soluble intravenous anaesthetic.~Subjects: Up to 47 healthy male volunteers, aged 18-40 years.~Evaluations: Tolerability, adverse events, EEG effects, cardiovascular effects, electrocardiogram (ECG), excitatory phenomena, respiratory effects, laboratory safety blood analyses, pharmacodynamic and pharmacokinetic measurements.