A Study to Evaluate the Safety and Efficacy of Ultiva (Remifentanil Hydrochloride) in Pediatric Participants General Anesthetised

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy and safety of JNJ-268229 (Ultiva /Remifentanil Hydrochloride) in pediatric participants between 1 and 15 years of age during maintenance of general anesthesia.

Detailed Description
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This is multicenter, open-label (identity of assigned study drug will be known) one-arm study in pediatric participants receiving general anesthesia. The participants are children aged 1-15 years old, planned to undergo head and neck, thoracic (except heart), urological, orthopedic or plastic surgery. Approximately 80 participants will be enrolled in this study. These participants are divided into two groups by age (1-6 and 7-15 years old). Pharmacokinetic (what the body does to the drug,) blood samples will be collected from at least 3 participants between the ages of 1 and 6 years and at least 3 participants between the ages of 7 and 15 years from 15 minutes after the start of infusion to the end of infusion of the study drug . The study consists of 4 phases: screening phase, treatment phase, recovery phase and follow-up phase. Screening for eligible participants will be performed within 14 days before administration of the study drug. The safety and tolerability of study drug will be evaluated by physical examinations, electrocardiogram (ECG), clinical laboratory tests, vital signs, and adverse events (AEs) according to the Time and Events Schedule. Participants safety will be monitored throughout the study.

Official Title
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An Open-Label Study to Evaluate the Efficacy and Safety of JNJ-268229 in Pediatric Subjects General Anesthetised

Conditions
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Anesthesia

Intervention / Treatment
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* Drug: Remifentanil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants scheduled to receive surgery under general anesthesia, necessitating airway securing with tracheal intubation and analgesia with opioid analgesics American Society of Anesthesiologists (ASA) Physical Status Classification is I or II at the time of operation planning Participants scheduled to receive operations estimated to take 30 minutes or more from skin incision i.e. Head and neck, thoracic (except heart), intraperitoneal, ophthalmological, otorhinolaryngological, urological, orthopedic or plastic surgery Girls having undergone menarche are eligible only if the urine pregnancy test at the time of screening is negative Exclusion Criteria:- Chronic use of opioid analgesics or their use within 12 hours before the planned start of general anesthesia - Hypersensitivity to opioid analgesics or local anesthetics History of jaundice or unexplained fever induced by halogenated anesthetics Unstable hemodynamics (eg. congenital heart disease, congenital diaphragmatic hernia) Ideal body weight is not within the 10th to 90th percentile received an investigational drug (including investigational vaccines) or used an invasive investigational medical device within 90 days before the planned first dose of study drug or is currently enrolled in an investigational study

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 15 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Remifentanil (0.25 µg/kg/min)<br> | Drug: Remifentanil<br>* After intubation, continuous intravenous infusion of remifentanil (0.25 µg/kg/min) is started, while anesthesia is maintained with inhaled or intravenous anesthetics. In cases where sedation by general anesthetics and analgesia by lidocaine does not seem to provide a sufficient means of analgesia at the time of intubation, remifentanil may be used, beginning before intubation. The rate of infusion may be adjusted while monitoring the subject's general condition in 25% to 100% increments or in 25% to 50% decrements every 2 to 5 minutes, but should not exceed 1.3 µg/kg/min.<br>* Other names: remifentanil hydrochloride (JNJ-268229);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with positive response to skin incision | Positive response is defined by the presence of at least one of below listed conditions: Heart rate increased >20% above baseline (that is measured under stable hemodynamics after intubation, and 1-5 minutes before the planned start of skin incision) for >1 minute); Systolic blood pressure increased >20% above baseline (that is measured under stable hemodynamics after intubation, and 1-5 minutes before the planned start of skin incision) for >1 minute; Gross movement, swallowing, eye opening (if there are patches on the eyes, this assessment might be not evaluated) or grimacing and sweating, lachrymation or mydriasis. | 5-minute assessment period after skin incision | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hemodynamics stability | Heart Rate and Blood Pressure increased >20% above baseline that is measured under stable hemodynamics after intubation, and 1-5 minutes before the planned start of skin incision for less than or equal to 1 minute. | 5-60 minutes before the start of intubation, 1-5 minutes before the planned start of the first skin incision. and 240 minutes after completion of anesthesia or skin closure | 
| Drugs used to deal with insufficient anesthesia (inadequate anesthesia) or excessive anesthesia | The time interval between completion of anesthesia and extubation is calculated based on both the time upon completion of general anesthesia and the time upon completion of extubation and recorded. | Time interval between completion of anesthesia and extubation | 
| Assessment on analgesic effect | Assess an analgesic effect of JNJ-268229 during operation on 3-point ranging from effective / not effective / undeterminable generally. | 240 minutes after completion of anesthesia | 
| Total dose level of remifentanil | The overall use (including dose increase/decrease, time of dose increase/decrease and start time of single supplemental bolus injection, etc) of remifentanil will be recorded. | 1-5 minutes before the planned start of the first skin incision. and 240 minutes after completion of anesthesia or skin closure | 
| Total concomitant anesthetic dose level | The overall use (drug name, dose and start time, etc) of the inhaled or intravenous anesthetics used for general anesthesia | 1-5 minutes before the planned start of the first skin incision. and 240 minutes after completion of anesthesia or skin closure | 
| Time from completion of anesthesia to resumption of spontaneous respiration | The time taken from completion of anesthesia to resumption of spontaneous respiration is calculated based on both the time upon completion of general anesthesia and the time upon confirmation of resumed spontaneous respiration and recorded. | 1-5 minutes before the planned start of the first skin incision. and 240 minutes after completion of anesthesia or skin closure | 
| Time until arrival of Steward Postanesthetic Recovery Score at 6 | Recovery Score is rated as Consciousness,Airway and Movement | 240 minutes after completion of anesthesia or skin closure | 
| Time from completion of anesthesia to discharge from the recovery room | Anesthesia is calculated based on both the time upon completion of general anesthesia and the time upon discharge from the operating /recovery room. | 240 minutes after completion of anesthesia or skin closure | 
| Respiratory stability | Heart Rate and Blood Pressure increased >20% above baseline that is measured under stable hemodynamics after intubation, and 1-5 minutes before the planned start of skin incision for less than or equal to 1 minute. | 5-60 minutes before the start of intubation, 1-5 minutes before the planned start of the first skin incision. and 240 minutes after completion of anesthesia or skin closure | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Anesthesia, Remifentanil, Ultiva