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.
