Clinical Trials/NCT01210352

NCT01210352

Completed

Phase 3

An Open-Label, Non-randomized, Multicenter, Ascending Dose by Age, Single- and Multiple-Dose Evaluation of the Effectiveness, Safety, and Tolerability of Oral Liquid Oxymorphone HCl Immediate-Release Oral Liquid for Acute Postoperative Pain in Pediatric Subjects

Endo Pharmaceuticals8 sites in 1 country61 target enrollmentDecember 13, 2010

ConditionsPost Operative Pain

Interventionsoxymorphone HCl

Drugsoxymorphone HCl

Overview

Phase: Phase 3
Intervention: oxymorphone HCl
Conditions: Post Operative Pain
Sponsor: Endo Pharmaceuticals
Enrollment: 61
Locations: 8
Primary Endpoint: Pain Intensity Score of Oxymorphone IR Oral Liquid in Pediatric Subjects by Age Group and Time Points in Single Dose Phase
Status: Completed
Last Updated: 4 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

The purpose of this study is to evaluate the effectiveness, tolerability, and safety of oxymorphone immediate release (IR) oral liquid as an analgesic for acute postoperative pain in pediatric subjects.

This post marketing study was required by the FDA. Endo Pharmaceuticals Inc. no longer promotes opioids and no longer markets Opana® ER.

Registry

clinicaltrials.gov

Start Date

December 13, 2010

End Date

October 6, 2017

Last Updated

4 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Endo Pharmaceuticals

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Males or females between 2 to ≤12 years of age. Females of child-bearing potential must 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 peri- and post-pubertal females will be considered to be of child-bearing potential unless they are biologically sterile or surgically sterile for more than 1 year
•Subjects must be at least 10 kg and BMI ≤30
•Scheduled to have a surgery for which oral opioid analgesia will be needed to manage postoperative pain for at least 24 hours (Single-Dose Phase) or 48 hours (Multiple-Dose Phase)following intraoperative and/or postoperative parenteral analgesia
•Be hospital inpatients, expected to be hospitalized for at least 24 hours (Single-Dose Phase) and 48 hours (Multiple-Dose Phase) following the initial administration of oxymorphone immediate release
•Available lab results, either intraoperatively (prior to surgical incision) or from within 21 days preoperatively, for clinical chemistry and hematology laboratory analytes (the results must have been reviewed by the Investigator for study eligibility)
•Able to provide pain assessment evaluations using an age-appropriate instrument provided in the protocol
•On an intravenous analgesic regimen utilizing a short-acting opioid analgesic following surgery AND anticipated to be switched to an oral opioid as part of the analgesic regimen (according to institution SOC)
•Demonstrated the ability to tolerate clear fluids following surgery according to the SOC at each institution
•Informed of the nature of the study and written informed consent has been obtained from the legally responsible parent(s)/legal guardian(s)
•Provided assent in accordance with IRB requirements

Exclusion Criteria

•Known allergies or sensitivities to oxymorphone or other opioid analgesics
•Known sensitivity to any component of the study drug
•Life expectancy \<4 weeks
•Positive pregnancy test at screening (females of reproductive age only)
•Pregnant and/or lactating
•Cyanotic heart disease
•Respiratory, hepatic, renal, neurological, psychological disease, or any other clinically significant condition that would, in the Investigator's opinion, preclude participation in the study
•Preoperative opioids administered for a period of more than 72 hours in duration
•Abdominal trauma that would interfere with absorption of study drug
•Increased intracranial pressure

Arms & Interventions

CII Drug

Open Label

Intervention: oxymorphone HCl

Outcomes

Primary Outcomes

Pain Intensity Score of Oxymorphone IR Oral Liquid in Pediatric Subjects by Age Group and Time Points in Single Dose Phase

Time Frame: Baseline, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours post dose; and at the time of rescue

Descriptive Statistics of the Pain Intensity Difference (PID) by Age Group and Time Points in Single-Dose Phase

Time Frame: Baseline (prior to dose); 15, 30 minutes, 1, 1.5, 2, 3, 4, 6, 8, 12, and 24 hours post-dose; and at the time of rescue

Faces Pain Scale-Revised (FPS-R) was used for the 6 to ≤ 12 years age group, (0 = no pain and 10 = very much pain). Face, Legs, Activity, Cry, and Consolability (FLACC) behavior measurement was used for the 2 years to \< 6 years and 0 years to \< 2 years age groups, (0 = no pain and 10 = very much pain). PID was calculated as the pain intensity score at baseline minus the current pain intensity score at each corresponding time point.

Pain Intensity Score of Oxymorphone IR Oral Liquid in Pediatric Subjects by Age Group and Time Points in Multiple Dose Phase

Time Frame: Baseline, 0.5, 1, 1.5, 2, hours post dose, and immediately prior to all remaining doses administered through 48 hours after administration of the initial dose; and at time of rescue

Descriptive Statistics of Pain Intensity Difference (PID) by Age Group and Time Points in Multiple-Dose Phase

Time Frame: 0.5, 1, 1.5, 2, hours post dose 1 through to Dose 12, 0 Hour; End of Study/Early Termination

Faces Pain Scale-Revised (FPS-R) was used for the 6 to ≤ 12 years age group, (0 = no pain and 10 = very much pain). Face, Legs, Activity, Cry, and Consolability (FLACC) behavior measurement was used for the 2 years to \< 6 years and 0 years to \< 2 years age groups, (0 = no pain and 10 = very much pain). PID is calculated as the pain intensity score at baseline minus the current pain intensity score at each corresponding time point.

Number (%) of Subjects With Rescue Medication Use by Age and Dose Group in Multiple-Dose Phase

Time Frame: Rescue Medication Use

Rescue Medication Use in Multiple Dose Phase

Secondary Outcomes

Oxymorphone AUC0-t Following Single-Dose Administration of 0.05, 0.1, and 0.2 mg/kg Oxymorphone HCl Immediate-Release Oral Liquid in Children Aged 2 Years to ≤12 Years in the Single-Dose Phase(Serial blood samples were collected at time 0 (Baseline), at 15 and 30 minutes, and at 1, 1.5, 2, 4, 6, 8, 12, and 24 hours post-dose)
Oxymorphone AUC0-inf Following Single-Dose Administration of 0.05, 0.1, and 0.2 mg/kg Oxymorphone HCl Immediate-Release Oral Liquid in Children Aged 2 Years to ≤12 Years in the Single-Dose Phase(Serial blood samples were collected at time 0 (Baseline), at 15 and 30 minutes, and at 1, 1.5, 2, 4, 6, 8, 12, and 24 hours post-dose)
Oxymorphone AUC0-24 Following Single-Dose Administration of 0.05, 0.1, and 0.2 mg/kg Oxymorphone HCl Immediate-Release Oral Liquid in Children Aged 2 Years to ≤12 Years in the Single-Dose Phase(Serial blood samples were collected at time 0 (Baseline), at 15 and 30 minutes, and at 1, 1.5, 2, 4, 6, 8, 12, and 24 hours post-dose)
Dose-Normalized Oxymorphone CL/F Following Single-Dose Administration of 0.05, 0.1, and 0.2 mg/kg Oxymorphone HCl Immediate-Release Oral Liquid in Children Aged 2 Years to ≤12 Years in the Single-Dose Phase(Serial blood samples were collected at time 0 (Baseline), at 15 and 30 minutes, and at 1, 1.5, 2, 4, 6, 8, 12, and 24 hours post-dose)
Oxymorphone AUC0-t Following Multiple-Dose Administration of 0.2 mg/kg Oxymorphone HCl Immediate-Release Oral Liquid in Children Aged 2 Years to ≤12 Years in the Multiple-Dose Phase From Dose 1 and Dose 7(Serial blood samples were collected at: time 0 (Baseline), at 0.5, 1, 1.5, and 2 hours post-Dose 1, immediately prior to Doses 2, 3, 4, 5, 6, 7, and at 0.5, 1, 1.5, and 2 hours post-Dose 7)
Oxymorphone Cmax Following Single-Dose Administration of 0.05, 0.1, and 0.2 mg/kg Oxymorphone HCl Immediate-Release Oral Liquid in Children Aged 2 Years to ≤12 Years in the Single-Dose Phase(Serial blood samples were collected at time 0 (Baseline), at 15 and 30 minutes, and at 1, 1.5, 2, 4, 6, 8, 12, and 24 hours post-dose)
Oxymorphone Tmax Following Single-Dose Administration of 0.05, 0.1, and 0.2 mg/kg Oxymorphone HCl Immediate-Release Oral Liquid in Children Aged 2 Years to ≤12 Years in the Single-Dose Phase(Serial blood samples were collected at time 0 (Baseline), at 15 and 30 minutes, and at 1, 1.5, 2, 4, 6, 8, 12, and 24 hours post-dose)
Oxymorphone Clast Following Single-Dose Administration of 0.05, 0.1, and 0.2 mg/kg Oxymorphone HCl Immediate-Release Oral Liquid in Children Aged 2 Years to ≤12 Years in the Single-Dose Phase(Serial blood samples were collected at time 0 (Baseline), at 15 and 30 minutes, and at 1, 1.5, 2, 4, 6, 8, 12, and 24 hours post-dose)
Oxymorphone Tlast Following Single-Dose Administration of 0.05, 0.1, and 0.2 mg/kg Oxymorphone HCl Immediate-Release Oral Liquid in Children Aged 2 Years to ≤12 Years in the Single-Dose Phase(Serial blood samples were collected at time 0 (Baseline), at 15 and 30 minutes, and at 1, 1.5, 2, 4, 6, 8, 12, and 24 hours post-dose)
Oxymorphone Tmax Following Multiple-Dose Administration of 0.2 mg/kg Oxymorphone HCl Immediate-Release Oral Liquid in Children Aged 2 Years to ≤12 Years in the Multiple-Dose Phase From Dose 1 and Dose 7(Serial blood samples were collected at: time 0 (Baseline), at 0.5, 1, 1.5, and 2 hours post-Dose 1, immediately prior to Doses 2, 3, 4, 5, 6, 7, and at 0.5, 1, 1.5, and 2 hours post-Dose 7)
Oxymorphone Tlast Following Multiple-Dose Administration of 0.2 mg/kg Oxymorphone HCl Immediate-Release Oral Liquid in Children Aged 2 Years to ≤12 Years in the Multiple-Dose Phase From Dose 1 and Dose 7(Serial blood samples were collected at: time 0 (Baseline), at 0.5, 1, 1.5, and 2 hours post-Dose 1, immediately prior to Doses 2, 3, 4, 5, 6, 7, and at 0.5, 1, 1.5, and 2 hours post-Dose 7)
Oxymorphone t1/2 Following Multiple-Dose Administration of 0.2 mg/kg Oxymorphone HCl Immediate-Release Oral Liquid in Children Aged 2 Years to ≤12 Years in the Multiple-Dose Phase From Dose 1 and Dose 7(Serial blood samples were collected at: time 0 (Baseline), at 0.5, 1, 1.5, and 2 hours post-Dose 1, immediately prior to Doses 2, 3, 4, 5, 6, 7, and at 0.5, 1, 1.5, and 2 hours post-Dose 7)
Oxymorphone t1/2 Following Single-Dose Administration of 0.05, 0.1, and 0.2 mg/kg Oxymorphone HCl Immediate-Release Oral Liquid in Children Aged 2 Years to ≤12 Years in the Single-Dose Phase(Serial blood samples were collected at time 0 (Baseline), at 15 and 30 minutes, and at 1, 1.5, 2, 4, 6, 8, 12, and 24 hours post-dose)
Oxymorphone Clast Following Multiple-Dose Administration of 0.2 mg/kg Oxymorphone HCl Immediate-Release Oral Liquid in Children Aged 2 Years to ≤12 Years in the Multiple-Dose Phase From Dose 1 and Dose 7(Serial blood samples were collected at: time 0 (Baseline), at 0.5, 1, 1.5, and 2 hours post-Dose 1, immediately prior to Doses 2, 3, 4, 5, 6, 7, and at 0.5, 1, 1.5, and 2 hours post-Dose 7)
6 Beta-Hydroxyoxymorphone Tmax Following Single-Dose Administration of 0.05, 0.1, and 0.2 mg/kg Oxymorphone HCl Immediate-Release Oral Liquid in Children Aged 2 Years to ≤12 Years in the Single-Dose Phase(Serial blood samples were collected at time 0 (Baseline), at 15 and 30 minutes, and at 1, 1.5, 2, 4, 6, 8, 12, and 24 hours post-dose)
6 Beta-Hydroxyoxymorphone Clast Following Single-Dose Administration of 0.05, 0.1, and 0.2 mg/kg Oxymorphone HCl Immediate-Release Oral Liquid in Children Aged 2 Years to ≤12 Years in the Single-Dose Phase(Serial blood samples were collected at time 0 (Baseline), at 15 and 30 minutes, and at 1, 1.5, 2, 4, 6, 8, 12, and 24 hours post-dose)
6 Beta-Hydroxyoxymorphone Tlast Following Single-Dose Administration of 0.05, 0.1, and 0.2 mg/kg Oxymorphone HCl Immediate-Release Oral Liquid in Children Aged 2 Years to ≤12 Years in the Single-Dose Phase(Serial blood samples were collected at time 0 (Baseline), at 15 and 30 minutes, and at 1, 1.5, 2, 4, 6, 8, 12, and 24 hours post-dose)
6 Beta-Hydroxyoxymorphone AUC0-t Following Single-Dose Administration of 0.05, 0.1, and 0.2 mg/kg Oxymorphone HCl Immediate-Release Oral Liquid in Children Aged 2 Years to ≤12 Years in the Single-Dose Phase(Serial blood samples were collected at time 0 (Baseline), at 15 and 30 minutes, and at 1, 1.5, 2, 4, 6, 8, 12, and 24 hours post-dose)
6 Beta-Hydroxyoxymorphone AUC0-inf Following Single-Dose Administration of 0.05, 0.1, and 0.2 mg/kg Oxymorphone HCl Immediate-Release Oral Liquid in Children Aged 2 Years to ≤12 Years in the Single-Dose Phase(Serial blood samples were collected at time 0 (Baseline), at 15 and 30 minutes, and at 1, 1.5, 2, 4, 6, 8, 12, and 24 hours post-dose)
6 Beta-Hydroxyoxymorphone AUC0-24 Following Single-Dose Administration of 0.05, 0.1, and 0.2 mg/kg Oxymorphone HCl Immediate-Release Oral Liquid in Children Aged 2 Years to ≤12 Years in the Single-Dose Phase(Serial blood samples were collected at time 0 (Baseline), at 15 and 30 minutes, and at 1, 1.5, 2, 4, 6, 8, 12, and 24 hours post-dose)
Dose-Normalized Oxymorphone V/F Following Single-Dose Administration of 0.05, 0.1, and 0.2 mg/kg Oxymorphone HCl Immediate-Release Oral Liquid in Children Aged 2 Years to ≤12 Years in the Single-Dose Phase(Serial blood samples were collected at time 0 (Baseline), at 15 and 30 minutes, and at 1, 1.5, 2, 4, 6, 8, 12, and 24 hours post-dose)
Oxymorphone Cmax Following Multiple-Dose Administration of 0.2 mg/kg Oxymorphone HCl Immediate-Release Oral Liquid in Children Aged 2 Years to ≤12 Years in the Multiple-Dose Phase From Dose 1 and Dose 7(Serial blood samples were collected at: time 0 (Baseline), at 0.5, 1, 1.5, and 2 hours post-Dose 1, immediately prior to Doses 2, 3, 4, 5, 6, 7, and at 0.5, 1, 1.5, and 2 hours post-Dose 7)
Oxymorphone AUC0-inf Following Multiple-Dose Administration of 0.2 mg/kg Oxymorphone HCl Immediate-Release Oral Liquid in Children Aged 2 Years to ≤12 Years in the Multiple-Dose Phase From Dose 1 and Dose 7(Serial blood samples were collected at: time 0 (Baseline), at 0.5, 1, 1.5, and 2 hours post-Dose 1, immediately prior to Doses 2, 3, 4, 5, 6, 7, and at 0.5, 1, 1.5, and 2 hours post-Dose 7)
Oxymorphone AUC0-24 Following Multiple-Dose Administration of 0.2 mg/kg Oxymorphone HCl Immediate-Release Oral Liquid in Children Aged 2 Years to ≤12 Years in the Multiple-Dose Phase From Dose 1 and Dose 7(Serial blood samples were collected at: time 0 (Baseline), at 0.5, 1, 1.5, and 2 hours post-Dose 1, immediately prior to Doses 2, 3, 4, 5, 6, 7, and at 0.5, 1, 1.5, and 2 hours post-Dose 7)
6 Beta-Hydroxyoxymorphone Cmax Following Single-Dose Administration of 0.05, 0.1, and 0.2 mg/kg Oxymorphone HCl Immediate-Release Oral Liquid in Children Aged 2 Years to ≤12 Years in the Single-Dose Phase(Serial blood samples were collected at time 0 (Baseline), at 15 and 30 minutes, and at 1, 1.5, 2, 4, 6, 8, 12, and 24 hours post-dose)
6 Beta-Hydroxyoxymorphone t1/2 Following Single-Dose Administration of 0.05, 0.1, and 0.2 mg/kg Oxymorphone HCl Immediate-Release Oral Liquid in Children Aged 2 Years to ≤12 Years in the Single-Dose Phase(Serial blood samples were collected at time 0 (Baseline), at 15 and 30 minutes, and at 1, 1.5, 2, 4, 6, 8, 12, and 24 hours post-dose)
Dose-Normalized 6 Beta-Hydroxyoxymorphone CL/F Following Single-Dose Administration of 0.05, 0.1, and 0.2 mg/kg Oxymorphone HCl Immediate-Release Oral Liquid in Children Aged 2 Years to ≤12 Years in the Single-Dose Phase(Serial blood samples were collected at time 0 (Baseline), at 15 and 30 minutes, and at 1, 1.5, 2, 4, 6, 8, 12, and 24 hours post-dose)
Dose-Normalized 6 Beta-Hydroxyoxymorphone V/F Following Single-Dose Administration of 0.05, 0.1, and 0.2 mg/kg Oxymorphone HCl Immediate-Release Oral Liquid in Children Aged 2 Years to ≤12 Years in the Single-Dose Phase(Serial blood samples were collected at time 0 (Baseline), at 15 and 30 minutes, and at 1, 1.5, 2, 4, 6, 8, 12, and 24 hours post-dose)
6 Beta-Hydroxyoxymorphone Cmax Following Multiple-Dose Administration of 0.2 mg/kg Oxymorphone HCl Immediate-Release Oral Liquid in Children Aged 2 Years to ≤12 Years in the Multiple-Dose Phase From Dose 1 and Dose 7(Serial blood samples were collected at: time 0 (Baseline), at 0.5, 1, 1.5, and 2 hours post-Dose 1, immediately prior to Doses 2, 3, 4, 5, 6, 7, and at 0.5, 1, 1.5, and 2 hours post-Dose 7)
6 Beta-Hydroxyoxymorphone Tmax Following Multiple-Dose Administration of 0.2 mg/kg Oxymorphone HCl Immediate-Release Oral Liquid in Children Aged 2 Years to ≤12 Years in the Multiple-Dose Phase From Dose 1 and Dose 7(Serial blood samples were collected at: time 0 (Baseline), at 0.5, 1, 1.5, and 2 hours post-Dose 1, immediately prior to Doses 2, 3, 4, 5, 6, 7, and at 0.5, 1, 1.5, and 2 hours post-Dose 7)
6 Beta-Hydroxyoxymorphone Clast Following Multiple-Dose Administration of 0.2 mg/kg Oxymorphone HCl Immediate-Release Oral Liquid in Children Aged 2 Years to ≤12 Years in the Multiple-Dose Phase From Dose 1 and Dose 7(Serial blood samples were collected at: time 0 (Baseline), at 0.5, 1, 1.5, and 2 hours post-Dose 1, immediately prior to Doses 2, 3, 4, 5, 6, 7, and at 0.5, 1, 1.5, and 2 hours post-Dose 7)
6 Beta-Hydroxyoxymorphone Tlast Following Multiple-Dose Administration of 0.2 mg/kg Oxymorphone HCl Immediate-Release Oral Liquid in Children Aged 2 Years to ≤12 Years in the Multiple-Dose Phase From Dose 1 and Dose 7(Serial blood samples were collected at: time 0 (Baseline), at 0.5, 1, 1.5, and 2 hours post-Dose 1, immediately prior to Doses 2, 3, 4, 5, 6, 7, and at 0.5, 1, 1.5, and 2 hours post-Dose 7)
6 Beta-Hydroxyoxymorphone AUC0-t Following Multiple-Dose Administration of 0.2 mg/kg Oxymorphone HCl Immediate-Release Oral Liquid in Children Aged 2 Years to ≤12 Years in the Multiple-Dose Phase From Dose 1 and Dose 7(Serial blood samples were collected at: time 0 (Baseline), at 0.5, 1, 1.5, and 2 hours post-Dose 1, immediately prior to Doses 2, 3, 4, 5, 6, 7, and at 0.5, 1, 1.5, and 2 hours post-Dose 7)
6 Beta-Hydroxyoxymorphone AUC0-inf Following Multiple-Dose Administration of 0.2 mg/kg Oxymorphone HCl Immediate-Release Oral Liquid in Children Aged 2 Years to ≤12 Years in the Multiple-Dose Phase From Dose 1 and Dose 7(Serial blood samples were collected at: time 0 (Baseline), at 0.5, 1, 1.5, and 2 hours post-Dose 1, immediately prior to Doses 2, 3, 4, 5, 6, 7, and at 0.5, 1, 1.5, and 2 hours post-Dose 7)
6 Beta-Hydroxyoxymorphone AUC0-24 Following Multiple-Dose Administration of 0.2 mg/kg Oxymorphone HCl Immediate-Release Oral Liquid in Children Aged 2 Years to ≤12 Years in the Multiple-Dose Phase From Dose 1 and Dose 7(Serial blood samples were collected at: time 0 (Baseline), at 0.5, 1, 1.5, and 2 hours post-Dose 1, immediately prior to Doses 2, 3, 4, 5, 6, 7, and at 0.5, 1, 1.5, and 2 hours post-Dose 7)
6 Beta-Hydroxyoxymorphone t1/2 Following Multiple-Dose Administration of 0.2 mg/kg Oxymorphone HCl Immediate-Release Oral Liquid in Children Aged 2 Years to ≤12 Years in the Multiple-Dose Phase From Dose 1 and Dose 7(Serial blood samples were collected at: time 0 (Baseline), at 0.5, 1, 1.5, and 2 hours post-Dose 1, immediately prior to Doses 2, 3, 4, 5, 6, 7, and at 0.5, 1, 1.5, and 2 hours post-Dose 7)