Safety, Tolerability, Effectiveness, and Pharmacokinetic Data in Opioid-experienced Children

Study Overview
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Brief Summary
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The purpose of this study was to assess the safety and pharmacokinetics (single- and multiple-dose) of oxymorphone ER for the relief of moderate to severe pain in pediatric participants ages 7 - ≤17 years old requiring a continuous, around-the-clock (ATC) opioid treatment for an extended period.

Official Title
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A Multicenter Study of the Safety, Tolerability, Effectiveness, and Pharmacokinetics of Oxymorphone HCL Extended-Release Tablets in Pediatric Subjects Requiring an Around-The-Clock Opioid for an Extended Period of Time

Conditions
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Chronic Pain, Postsurgical Pain

Intervention / Treatment
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* Drug: Oxymorphone hydrochloride (HCl)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Were males or females 7 - ≤17 years of age. Females of childbearing potential had to be practicing abstinence or using a medically acceptable form of contraception (eg, intrauterine device, hormonal birth control, or double barrier method). For the purpose of this study, all menstruating females were considered to be of childbearing potential unless they were biologically sterile or surgically sterile for more than 1 year. Had chronic pain (malignant and/or nonmalignant) or postsurgical pain expected to require ATC opioid analgesia for up to 12 weeks with at least 10 mg per day oxymorphone ER (approximately equal to 30 mg per day oral MSE). Had a body weight at least 18 kg. Were able to swallow oxymorphone ER tablets. Had laboratory results from within 21 days prior to Baseline available including clinical chemistry and hematology laboratory analytes. Intraoperative (prior to surgical incision) labs were acceptable provided the results had been reviewed by the investigator for study eligibility prior to dosing. Subjects with postsurgical pain were prescribed a parenteral analgesic regimen utilizing a short-acting opioid analgesic AND were anticipated to be switched to an oral opioid for an extended period of time (according to institutions standard of care). Were able to provide pain assessment evaluations using age-appropriate instruments provided in the protocol. Had been informed of the nature of the study and informed consent and assent (as appropriate) have been obtained from the legally responsible parent(s)/legal guardian(s) and subject, respectively, in accordance with IRB requirements. To participate in the PK Period, subjects had: Been hospital inpatients, expected to be hospitalized for up to 72 hours following the initial administration of oxymorphone ER. An indwelling access catheter in place for blood sampling. Exclusion Criteria: Had known allergies or sensitivities to oxymorphone or other opioid analgesics. Had a known sensitivity to any component of the oxymorphone ER. Had a life expectancy <3 months. Was pregnant and/or lactating. Had cyanotic heart disease. Had respiratory, hepatic, renal, neurological, psychological disease, or any other clinically significant condition that would, in the Investigator's opinion, preclude participation in the study. Had abdominal trauma that would interfere with absorption of oxymorphone ER. Had increased intracranial pressure. Had a respiratory condition requiring intubation. Had a history of uncontrolled seizures that were not managed with anticonvulsants. Had prior history of substance abuse or alcohol abuse. Had taken a monoamine oxidase inhibitor (MAOI) within 14 days prior to the start of oxymorphone ER. Had taken oxycodone or oxymorphone within 48 hours prior to Baseline. The investigator anticipated that the subject and/or parent(s)/legal guardian(s) was unable to comply with the protocol. The subject (and/or parent[s]/legal guardian[s]) was (were) unable to communicate effectively with study personnel.

Ages Eligible for Study
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Minimum Age: 7 Years
Maximum Age: 17 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
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Pediatric Age Groups: 7 to ≤12 years<br>Participants expected to require ATC opioids for an extended period of time | Drug: Oxymorphone hydrochloride (HCl)<br>* Opioid<br>* Other names: OPANA® ER (oxymorphone HCl) Extended-Release Tablets;|
| Active Comparator: Pediatric Age Groups: 13 to ≤17 years<br>Participants expected to require ATC opioids for an extended period of time | Drug: Oxymorphone hydrochloride (HCl)<br>* Opioid<br>* Other names: OPANA® ER (oxymorphone HCl) Extended-Release Tablets;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain Intensity Score using FPS-R | Faces Pain Scale - Revised (FPS-R) self-report measure used to assess pain intensity in participants ages 7 - ≤12 years old, consists of 6 faces, visually representing increasing changes in pain intensity bounded on the left by no pain and on the right by very much pain. | 14 Days Post Last Dose | 
| Pain Intensity Score using NRS-11 | Numerical Rating Scale (NRS-11) is an 11-point categorical numerical rating scale to assess pain intensity in participants ages 13 - ≤17 years old. The scale is anchored on the left with No Pain and is anchored on the right with Worst Possible Pain. | 14 Days Post Last Dose |