Safety of Twice Daily Oxycodone Hydrochloride Controlled-release Tablets in Children With Moderate to Severe Malignant and/ or Nonmalignant Pain Requiring Opioids

Study Overview
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Brief Summary
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The purpose of this study is to characterize the safety of oxycodone hydrochloride (HCl) controlled-release (CR) tablets in opioid tolerant pediatric patients aged 6 to 16 years, inclusive, with moderate to severe malignant and/or nonmalignant pain requiring opioid therapy.

Official Title
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An Open-label, Multicenter Study of the Safety of Twice Daily Oxycodone Hydrochloride Controlled-release Tablets in Opioid Experienced Children From Ages 6 to 16 Years Old, Inclusive, With Moderate to Severe Malignant and/or Nonmalignant Pain Requiring Opioid Analgesics

Conditions
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Pain

Intervention / Treatment
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* Drug: Oxycodone HCl controlled-release tablets


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria include: Male and female patients aged 6 to 16 years, inclusive, who are expected to require ongoing around-the-clock opioid treatment equivalent to at least 20-mg daily dose of oxycodone for at least 2 weeks for management of moderate to severe (based on the investigator's judgment) malignant or nonmalignant pain. Patients must be opioid tolerant, ie, have been treated with opioids for at least the 5 consecutive days prior to dosing and with at least 20 mg daily of oxycodone or the equivalent during at least the last 48 hours prior to the start of study drug dosing and have tolerated the therapy, as demonstrated at the start of study drug dosing. Patients who are currently using transdermal fentanyl should have been on the patch for at least 3 days before removing the patch and oxycodone hydrochloride (HCl) controlled-release (CR) treatment can only be initiated at least 18 hours following the removal of the transdermal fentanyl patch. Patients must not require more than a 240-mg total daily dose of oxycodone HCl CR tablets. Patients must be willing and able to swallow the oxycodone HCl CR tablets whole. Patients must not be currently on an investigational medication/therapy at the start of screening or during the study. Exclusion Criteria include: Female patients who are pregnant or lactating. Patients who are allergic to oxycodone or have a history of allergies to other opioids (this criterion does not include patients who have experienced common opioid side effects [eg, nausea, constipation]). Patients who have received epidural opioids < 2 hours prior to the first dose of study drug or who have received epidural morphine < 12 hours prior to the first dose of study drug. Patients who are contraindicated for the use of opioids. Patients who are contraindicated for blood sampling. Patients who are currently being maintained on methadone for pain. Patients who have any planned surgery during the course of the study, with the exception of the placement of central or peripheral venous access devices. Patients who have had surgery within 5 days prior to Day 1 (day of first dose of study drug). Patients who, in the investigator's opinion, have an underlying gastrointestinal condition or other disorder that may predispose them to obstruction. Other protocol-specific inclusion/exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 16 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: Oxycodone HCl controlled-release<br>Oxycodone hydrochloride (HCl) controlled-release (CR) | Drug: Oxycodone HCl controlled-release tablets<br>* Oxycodone HCl controlled-release tablets at strengths of 10, 15, 20, 30, or 40 mg (20 mg - 240 mg daily) every 12 hours.<br>* Other names: OxyContin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Number of Participants With Adverse Events as a Measure of Safety. | Safety assessments consisted of reports of AEs, physical examinations, clinical laboratory test results, vital signs measurements, pulse oximetry (SpO2), and somnolence assessments. Safety variables were summarized descriptively within age group for the safety population. | Up to 4 weeks (during the study) and 7-10 days poststudy (safety follow-up assessment). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain Right Now Assessment by Patients Aged 6 to < 12 Years | Pain right now was assessed by patients aged 6 to <12 years using the Faces of Pain Scale-Revised (FPS-R). The FPS-R is a horizontal row of 6 faces representing pain intensity, with no hurt at the far left and hurts worst at the far right; the 6 intensities are scored as 0, 2, 4, 6, 8, or 10 (the patient was not shown the numbers associated with the faces). A score of 0 means no pain, and a 10 means very much pain. Pain right now was assessed by the patient at screening; after the first dose; and, thereafter, twice daily during the AM and PM, approximately at the time of each (morning and evening) dose of oxycodone HCl CR tablets during the study treatment. | Baseline to week 4 | 
| Pain Right Now Assessment by Patients Aged ≥ 12 to ≤ 16 Years | Pain right now was assessed by patients aged ≥ 12 to ≤ 16 years using the 100-mm visual analogue scale (VAS). The 100-mm VAS is a 100-mm line with 1 end marked no pain and the opposite end marked as pain as bad as it could be. The patient was asked to make a mark on that line indicating his or her level of pain. The pain right now 100-mm VAS score was defined as the distance (in mm) from the no pain end to the patient's mark. The scale is measured on a 100 mm line: a 0 means no pain and bigger numbers indicate more pain. Pain right now was assessed by the patient at screening; after the first dose; and, thereafter, twice daily during the AM and PM, approximately at the time of each (morning and evening) dose of oxycodone HCl CR tablets during the study treatment. | Baseline to week 4 | 
| Use of Supplemental Pain Medication | Supplemental opioid and nonopioid pain medications were permitted during the study as deemed appropriate by the investigator. The dose of supplemental analgesic medication allowed was at the discretion of the investigator and within appropriate dose ranges for age and weight. | Baseline to week 4 | 
| Parent/ Caregiver-Assessed Global Impression of Change (PGIC) | The PGIC rating score variable was collected on a 7-point scale ranging from 1 to 7 (where 1 = very much improved; and 7 = very much worse). The PGIC is designed to assess overall satisfaction with the treatment. The number and percent of parent/caregivers reporting each category of PGIC response at the final visit was summarized for the safety population within age group. | Baseline to week 4 or early discontinuation | 
| Parent/ Caregiver Assessed Functional Disability Inventory (FDI) for Patients Aged 6 to < 12 Years | The FDI is a validated tool used to evaluate the degree to which children have reduced physical and psychosocial functioning because of their pain difficulties in the previous 2 weeks. The FDI comprises 15 items. Responses to each item were scored using a 5-point Likert scale. The individual scores are: (0) no trouble, (1) a little trouble, (2) some trouble, (3) a lot of trouble, and (4) impossible. A total score (ranging from 0 to 60) for the 15 items was calculated, with lower scores indicating less functional disability. The FDI was performed by the parent/ caregiver. | Baseline to week 4 | 
| Parent/ Caregiver Assessed Functional Disability Inventory (FDI) for Patients Aged ≥ 12 to ≤ 16 Years | The FDI is a validated tool used to evaluate the degree to which children have reduced physical and psychosocial functioning because of their pain difficulties in the previous 2 weeks. The FDI comprises 15 items. Responses to each item were scored using a 5-point Likert scale. The individual scores are: (0) no trouble, (1) a little trouble, (2) some trouble, (3) a lot of trouble, and (4) impossible. A total score (ranging from 0 to 60) for the 15 items was calculated, with lower scores indicating less functional disability. The FDI was performed by the parent/ caregiver. | Baseline to week 4 | 
| Pharmacokinetics (PK) Data of Oxycodone Hydrochloride Controlled-release Tablets | A population PK analysis using sparse plasma concentration data in pediatric patients was conducted. Empirical Bayes estimates were used to calculate individual PK parameters. PK parameters were calculated and reported for each individual patient's first and last dose. Cmax was taken as the maximum simulated oxycodone concentration over the dosing interval and Cmin was the simulated oxycodone concentration when time was equal to 12 hours. Steady-state Cmin and Cmax were derived from the accumulation ratio. The following PK parameters are presented: Cmin / Cmax (minimum / maximum concentration); Cmin,ss / Cmax,ss (Cmin / Cmax at steady state); CAVGss (average concentration at steady state). | Day 1 - first dose [2-4 hrs post dose and 4-6 hrs post dose], week 4 - last dose [at pre-dose and at 2-4 hrs post dose] | 
| Pharmacokinetics (PK) Data of Oxycodone Hydrochloride Controlled-release Tablets - AUCtau and AUCss | A population PK analysis using sparse plasma concentration data in pediatric patients was conducted. Empirical Bayes estimates were used to calculate individual PK parameters. PK parameters were calculated and reported for each individual patient's first and last dose. First-dose area under the concentration-time curve (AUC) was derived from the accumulation ratio. For all calculations, the dosing interval was assumed to be 12 hours. The following PK parameters are presented: AUCtau (area under the concentration-time curve from time zero to time equal to dosing interval); AUCss (AUC at steady state). | Day 1 - first dose [2-4 hrs post dose and 4-6 hrs post dose], week 4 - last dose [at pre-dose and at 2-4 hrs post dose] | 
| Pharmacokinetics (PK) Data of Oxycodone Hydrochloride Controlled-release Tablets - Time to Maximum Concentration (Tmax) | A population PK analysis using sparse plasma concentration data in pediatric patients was conducted. Empirical Bayes estimates were used to calculate individual PK parameters. PK parameters were calculated and reported for each individual patient's first and last dose. | Day 1 - first dose [2-4 hrs post dose and 4-6 hrs post dose], week 4 - last dose [at pre-dose and at 2-4 hrs post dose] | 
| Pharmacokinetics (PK) Data of Oxycodone Hydrochloride Controlled-release Tablets - Accumulation Ratio | A population PK analysis using sparse plasma concentration data in pediatric patients was conducted. Empirical Bayes estimates were used to calculate individual PK parameters. PK parameters were calculated and reported for each individual patient's first and last dose. The accumulation ratio is used to derive steady-state Cmin and Cmax and first-dose area under the concentration-time curve (AUCtau). | Day 1 - first dose [2-4 hrs post dose and 4-6 hrs post dose], week 4 - last dose [at pre-dose and at 2-4 hrs post dose] | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Malignant pain, Nonmalignant pain, Pediatric, Opioid, Moderate to severe malignant or nonmalignant pain