Evaluate The Pharmacokinetics and Safety Of Oxycodone Oral Solution In Pediatric and Adolescent Subjects
Condition: Pain
Study type: Interventional
Phase: Phase 4

Summary: 
      The objective of this study is to characterize the pharmacokinetics and to evaluate the
      safety of single and multiple doses of Oxycodone Oral Solution in pediatric and adolescent
      subjects for postoperative pain.
    

Detailed description: 
      This is a Phase IV study to characterize the pharmacokinetics and to evaluate the safety of
      Oxycodone Oral Solution administered to pediatric and adolescent subjects for postoperative
      pain. It is an open label, multicenter study conducted at up to 10 sites. Subjects will be
      enrolled preoperatively up to 14 days before surgery with the expectation that they will
      require intravenous (IV) access after the surgery for at least 24 hours and postoperative
      analgesia with an opiate level medication. After dosing with Oxycodone Oral Solution (0.1
      mg/kg for children ages 2 to 6, 0.08 mg/kg for ages 7 to 12, 0.07 mg/kg for ages 13 to 17,
      and a dose to be determined based on pharmacokinetic (PK) modeling from the interim analyses
      for subjects under age 2), subjects will be carefully monitored for safety. A total of 110
      pediatric and adolescent male or female subjects will be enrolled, including a minimum of 20
      subjects under age 2 (5 subjects ages 0 to <2 months, 5 subjects ages 2 to <6 months, and 10
      subjects ages 6 months to <2 years), 30 ages 2 to 6 years, 30 ages 7 to 12 years and 30 ages
      13 to <17 years. Subjects within each age group will be evenly distributed by age and gender.

      An interim analysis will be run after 10 subjects ages 2 to 6 years, 10 ages 7 to 12 years
      and 10 ages 13 to <17 years have completed the study. The interim analysis will include PK,
      pulse oximetry readings, vital sign measurements, adverse events (AEs) and concomitant
      medications. The dose of Oxycodone Oral Solution that the subjects ages 6 months to <2 years
      will receive will be based on PK modeling from the interim analysis.

      An additional interim analysis will be run after at least half of the subjects aged 6 months
      to <2 years have completed the study. The interim analysis will include PK, pulse oximetry
      readings, vital sign measurements, AEs and concomitant medications. The dose of Oxycodone
      Oral Solution that the subjects ages 0 to <2 months and 2 months to <6 months will receive
      will be based on PK modeling from the interim analysis.

      The study will consist of a Screening period within 14 days of surgery; a predose check-in
      (Day -1); a treatment period after surgery (Day 1, Time Zero); and an End of Study
      assessment. The total duration of the study, excluding Screening, will be approximately 1
      full day.

      Eligible subjects who provide assent (7 to <17 years old) and whose parent(s) or legal
      guardian(s) provide consent as required will have study assessments performed at Screening.
      Following surgery, subjects will receive standard care, including parenteral analgesia with a
      nonoxycodone, nonoxymorphone medication that will not interfere with the measurement or
      metabolism of oxycodone. At this time (during Day -1), they will have a predose check-in to
      have eligibility confirmed.

      After subjects ages 2 to <17 have been postoperatively cleared to transition to oral pain
      medication, Oxycodone Oral Solution will be administered at Time Zero of Day 1 in place of
      the standard analgesic medication. The first 10 subjects in each of the 2 to 6, 7 to 12 and
      13 to <17 age groups, who will be included in the first interim analysis, will only receive 1
      dose of Oxycodone Oral Solution. Subjects in these age groups enrolled in the study after the
      interim analysis is completed may receive additional doses every 4-6 hours as needed. If pain
      control is inadequate with Oxycodone Oral Solution, the investigator may administer an IV
      dose of ketorolac (0.5 mg/kg) every 6 hours or an IV dose of Morphine Sulfate (0.1 mg/kg)
      every 4 hours as rescue medication for breakthrough pain after dosing. Use of other rescue
      pain medication is permissible in accordance with hospital pain management guidelines or
      facilities standard of care. Any rescue medications used will be provided by the study site
      pharmacy.

      After subjects under age 2 have been postoperatively cleared to transition to oral pain
      medication, they will receive a single dose of Oxycodone Oral Solution at Time Zero of Day 1
      in place of the standard analgesic medication. The dose will be determined based on PK
      modeling from the interim analyses. If pain control is inadequate with Oxycodone Oral
      Solution, as indicated by a score of moderate to severe (4-10) on the FLACC, the subject will
      be given Fentanyl via Nurse-Controlled Analgesia (NCA). The Fentanyl will be provided by the
      study site pharmacy.

      Subjects will undergo an End-of-Study assessment at least 24 hours after receiving the first
      dose of Oxycodone Oral Solution. At that time, if the study staff determines that it is safe
      to do so, subjects will be discharged from the study.

      Safety will be assessed by monitoring AEs, clinical laboratory test results, vital sign
      measurements, temperature, pulse oximetry, and physical examination findings.

      The Faces, Legs, Activity, Crying, Consolability Scale (FLACC) will be used to measure pain
      prior to and 20, 40, 60, 90, 120, 180, and 240 minutes after the dose of Oxycodone Oral
      Solution in subjects under age 2. The FLACC will also be administered prior to the subject
      receiving each dose of Fentanyl.

      Serial blood samples for PK analysis will be collected for the determination of plasma
      concentrations of oxycodone and its metabolites (noroxycodone, oxymorphone and
      noroxymorphone) prior to the first dose (within 15 minutes of dosing); 5, 15, 30, and 60
      minutes after dosing; and 2, 4, 6, 8, 12, and 24 hours after dosing. For subjects under age
      2, serial blood samples for PK analysis will be collected prior to the first dose (within 15
      minutes of dosing); 15, 30, and 60 minutes after dosing; and 2, 6, 12, and 24 hours after
      dosing.
    

Intervention name(s): Oxycodone
Intervention type(s): Drug
Intervention description(s): Pain
Intervention MeSH terms: Oxycodone
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: pharmacokinetics; safety