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

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

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.

Study Overview

• Status: Completed
• Conditions: Pain
• Intervention / Treatment: Drug: Oxycodone HCl controlled-release tablets

• Study Type: Interventional
• Enrollment (Actual): 155
• Phase: Phase 3

Contacts and Locations

Study Locations

• Greece
  • Athens, Greece, 115 27
    • Agia Sophia Children's Hospital
  • Athens, Greece, 115 27
    • Aglaia Kyriakou - Elpida Children's Oncology Unit
• Hungary
  • Budapest, Hungary, H-1094
    • Semmelweis Egyetem, II. sz. Gyermekgyógyászati Klinika
• Israel
  • Beersheba, Israel, 84101
    • Soroka University Medical Center
  • Haifa, Israel, 31096
    • Mayer Children Hospital, Rambam Medical Center
  • Jerusalem, Israel, 91120
    • Hadassah Medical Organization, Ein Kerem
  • Petaẖ Tiqwa, Israel, 49202
    • Schneider Children Medical Center of Israel
  • Ramat Gan, Israel, 52621
    • Sheba Medical Center
• New Zealand
  • Auckland
    • Grafton, Auckland, New Zealand, 1023
      • Starship Children's Health
• Romania
  • Targu Mures, Romania, 540136
    • Spitalul Clinic Judetean de Urgenta Targu Mures, Clinica pediatrie I
• Spain
  • Barcelona, Spain, 08025
    • Hospital de la Santa Creu I Sant Pau
• United Kingdom
  • Sheffield, United Kingdom, S10 2TH
    • Sheffield Children's Hospital
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Children's Hospital of Alabama
    • Mobile, Alabama, United States, 36604
      • University of South Alabama, Children's and Women's Hospital
  • Arizona
    • Phoenix, Arizona, United States, 85016
      • Phoenix Children's Hospital
  • California
    • Loma Linda, California, United States, 92354
      • Loma Linda University Medical Center
    • Los Angeles, California, United States, 90027
      • Children's Hospital Los Angeles
    • Orange, California, United States, 92868
      • Children's Hospital of Orange County
    • Palo Alto, California, United States, 94304
      • LS Packard Children's Hospital
    • Paramount, California, United States, 90723
      • Bayview Research Group, LLC
    • Sacramento, California, United States, 95817
      • Shriners Hospitals For Children Northern California
  • Colorado
    • Aurora, Colorado, United States, 80045
      • The Children's Hospital
  • Connecticut
    • Hartford, Connecticut, United States, 06106
      • Connecticut Children's Medical Center
  • Delaware
    • Wilmington, Delaware, United States, 19803
      • Alfred I. duPont Hospital for Children
  • Florida
    • Hollywood, Florida, United States, 33021
      • Memorial Regional Hospital
    • Miami, Florida, United States, 33136
      • Jackson Memorial Hospital/University of Miami
    • Tampa, Florida, United States, 33606
      • Tampa General Hospital
  • Illinois
    • Chicago, Illinois, United States, 60614
      • Children's Memorial Hospital
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky
  • Michigan
    • Grand Rapids, Michigan, United States, 49503
      • Helen DeVos Children's Hospital
  • Missouri
    • Saint Louis, Missouri, United States, 63141
      • St. John's Mercy Medical Center
  • New York
    • New York, New York, United States, 10016
      • New York University Langone Medical Center
    • Stony Brook, New York, United States, 11794
      • Stony Brook University Hospital
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Presbyterian Blume Pediatric Hematology and Oncology Clinic
    • Durham, North Carolina, United States, 22710
      • Duke University Medical Center
  • Ohio
    • Akron, Ohio, United States, 44308
      • Akron Children's Hospital
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • The Children's Hospital at OUMC
    • Oklahoma City, Oklahoma, United States, 73104
      • Department of Pediatrics, University of Oklahoma Health Sciences Center
  • Oregon
    • Portland, Oregon, United States, 97227
      • Legacy Emanuel Children's Hospital
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15224
      • Children's Hospital of Pittsburgh of UPMC
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Monroe Carell Jr. Children's Hospital at Vanderbilt
  • Texas
    • Dallas, Texas, United States, 75235
      • Children's Medical Ctr of Dallas
    • The Woodlands, Texas, United States, 77381
      • Research Facility
  • Utah
    • Salt Lake City, Utah, United States, 84113
      • Primary Children's Medical Center
  • Virginia
    • Norfolk, Virginia, United States, 23507
      • Children's Hospital of The King's Daughters
    • Richmond, Virginia, United States, 23298
      • Pediatric Hematology and Oncology, Virginia Commonwealth University Health System
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Children's Hospital of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 16 years (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Oxycodone HCl controlled-release; Oxycodone hydrochloride (HCl) controlled-release (CR)	Drug: Oxycodone HCl controlled-release tablets; Oxycodone HCl controlled-release tablets at strengths of 10, 15, 20, 30, or 40 mg (20 mg - 240 mg daily) every 12 hours.; Other Names: OxyContin

What is the study measuring?

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]

Collaborators and Investigators

• Sponsor: Purdue Pharma LP

Publications and helpful links

Helpful Links

• Product Information

Study record dates

Study Major Dates

• Study Start: November 1, 2010
• Primary Completion (ACTUAL): July 1, 2014
• Study Completion (ACTUAL): July 1, 2014

Study Registration Dates

• First Submitted: August 30, 2010
• First Submitted That Met QC Criteria: August 31, 2010
• First Posted (ESTIMATE): September 1, 2010

Study Record Updates

• Last Update Posted (ACTUAL): March 23, 2020
• Last Update Submitted That Met QC Criteria: March 19, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: Pediatric; Opioid; Nonmalignant pain; Malignant pain; Moderate to severe malignant or nonmalignant pain
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Oxycodone
• Other Study ID Numbers: OTR3001; 2010-020471-23 (EUDRACT_NUMBER)