Phase 3 N=61 Treatment

Effectiveness, Safety, and Tolerability Study of Oxymorphone Immediate Release (IR) Oral Liquid in Post Surgical Pediatric Subjects

Post Operative Pain

Bottom Line

View on ClinicalTrials.gov: NCT01210352 ↗

Enrolled (actual)

Serious AEs

6.6%

Results posted

May 2019

Primary outcome: Primary: Pain Intensity Score of Oxymorphone IR Oral Liquid in Pediatric Subjects by Age Group and Time Points in Single Dose Phase — 4.5; 3.4; 2.4; 3.5 score on a scale

Study Design & Population

Study type: Interventional
Phase: Phase 3
Interventions: oxymorphone HCl (Drug)
Age: Pediatric · 0+ yrs
Sex: All
Sponsor: Endo Pharmaceuticals
Primary completion: Oct 2017

Outcome Measures

Outcome	Result	p-value
PRIMARY Pain Intensity Score of Oxymorphone IR Oral Liquid in Pediatric Subjects by Age Group and Time Points in Single Dose Phase	4.5; 3.4; 2.4; 3.5; 1.2; 1.3	—
PRIMARY Descriptive Statistics of the Pain Intensity Difference (PID) by Age Group and Time Points in Single-Dose Phase	1.1; 2.1; 1.1; 1.6; 2.1; 2.0	—
PRIMARY Pain Intensity Score of Oxymorphone IR Oral Liquid in Pediatric Subjects by Age Group and Time Points in Multiple Dose Phase	3.1; 3.5; 2.7; 1.3; 2.0; 1.8	—
PRIMARY Descriptive Statistics of Pain Intensity Difference (PID) by Age Group and Time Points in Multiple-Dose Phase	0.4; 2.2; 0.9; 2.0; 1.1; 4.8	—
PRIMARY Number (%) of Subjects With Rescue Medication Use by Age and Dose Group in Multiple-Dose Phase	5; 2; 5; 4	—
SECONDARY 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	0.415; 0.33; 1.14; 1.76; 1.33; 3.16	—
SECONDARY 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	2.7; 2.64; 1.38; 1.45; 2.49; 1.59	—
SECONDARY 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	0.0759; 0.0618; 0.11; 0.0671; 0.269; 0.645	—
SECONDARY 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	15.4; 13.2; 18; 16; 12.6; 18.4	—
SECONDARY 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	2.56; 1.69; 3.01; 3.99; 5.32; 9.37	—
SECONDARY 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	NA; 3.22; 3.01; 3.69; 6.92; 14.3	—
SECONDARY 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	3.75; 2.65; 3.01; 3.69; 6.11; 14	—
SECONDARY 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	NA; 5.01; 7.5; 4.38; 5.13; 4.39	—
SECONDARY 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	31.2; 26.4	—
SECONDARY 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	205; 154	—
SECONDARY 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	1.46; 2.58; 2.66	—
SECONDARY 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	1.37; 0.967; 1.21	—
SECONDARY 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	0.452; 0.508; 2.3	—
SECONDARY 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	4; 4.47; 2.09	—
SECONDARY 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	3.49; 3.88; 4.24	—
SECONDARY 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	4.01; 4.53	—
SECONDARY 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	4.01; 4.53	—
SECONDARY 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	2.18; 1.17	—
SECONDARY 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	0.104; 0.1; 0.384; 0.437; 0.603; 0.587	—
SECONDARY 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	2.86; 2.91; 1.38; 1.86; 3.08; 1.93	—
SECONDARY 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	0.0453; 0.0418; 0.0568; 0.0332; 0.204; 0.0994	—
SECONDARY 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	9.66; 8.86; 14.4; 16.1; 12.6; 18.4	—
SECONDARY 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	0.459; 0.467; 1.22; 1.27; 2.64; 2.26	—
SECONDARY 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	1.83; 1.11; 0.535; 1.76; 7.58; 2.76	—
SECONDARY 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	1.09; 1.09; 1.08; 1.45; 3.08; 2.61	—
SECONDARY 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	20.5; 4.48; 2.31; 8.67; 18.7; 5.18	—
SECONDARY 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	70.7; 65	—
SECONDARY 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	631; 575	—
SECONDARY 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	0.547; 0.829; 1.41	—
SECONDARY 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	1.67; 1.37; 1.36	—
SECONDARY 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	0.201; 0.225; 1.25	—
SECONDARY 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	3.97; 4.47; 2.09	—
SECONDARY 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	1.35; 1.61; 2.25	—
SECONDARY 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	2.15; 1.79; 7.66	—
SECONDARY 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	2.11; 1.78; 7.38	—
SECONDARY 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	3.61; 1.42; 4.9	—

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.

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
Line in place for blood sampling

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
Respiratory condition requiring intubation
History of uncontrolled seizures that are not being managed with anticonvulsants
Significant prior history of substance abuse or alcohol abuse
Received any investigational drug within 30 days prior to the first dose of study drug, or are scheduled to receive an investigational drug other than oxymorphone HCl immediate-release oral liquid during the course of the study
Received a monoamine oxidase inhibitor (MAOI) within 14 days prior to the start of study drug
Received oxycodone or oxymorphone within 48 hours prior to study start
Investigator anticipates that the subject and/or parent(s)/legal guardian(s) would be unable to comply with the protocol
Subject (and/or parent[s]/legal guardian[s]) is(are) unable to communicate effectively with study personnel at an age-appropriate level

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT01210352). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.