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

• ClinicalTrials.gov Identifier: NCT01210352
• Recruitment Status: Completed
• First Posted: September 28, 2010
• Results First Posted: May 7, 2019
• Last Update Posted: May 7, 2019
• Sponsor: Endo Pharmaceuticals
• Information provided by (Responsible Party): Endo Pharmaceuticals

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Post Operative Pain	Drug: oxymorphone HCl	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 61 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: December 13, 2010
• Actual Primary Completion Date: October 6, 2017
• Actual Study Completion Date: October 6, 2017

Arms and Interventions

Arm	Intervention/treatment
Experimental: CII Drug; Open Label	Drug: oxymorphone HCl; Comparison of different dosages of drug, 0.05mg/kg, 0.10mg/kg, 0.15mg/kg or 0.20mg/kg oral liquid oxymorphone; Other Name: Opana

Outcome Measures

Primary Outcome Measures :

1. 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 ]

   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).

2. 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.

3. 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 ]

   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)

4. 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.

5. 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 Outcome Measures :

1. 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 [ Time Frame: 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 ]
   Cmax: Maximum plasma concentration; the highest concentration observed during a dosage interval
2. 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 [ Time Frame: 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 ]
   Tmax: The time at which Cmax was observed
3. 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 [ Time Frame: 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 ]
   Clast: Minimum plasma concentration; the last concentration observed during a dosage interval
4. 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 [ Time Frame: 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 ]
   Tlast: The time at which Clast was observed
5. 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 [ Time Frame: 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 ]
   AUC0-t: Area under the concentration versus time curve from time 0 to the last measured concentration (Clast) calculated by linear trapezoidal rule
6. 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 [ Time Frame: 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 ]
   AUC0-inf: Area under the concentration versus time curve from time 0 to infinity, calculated as AUC0-t + Clast/λn
7. 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 [ Time Frame: 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 ]
   AUC0-24: Area under the concentration versus time curve from time 0 to 24 hours calculated by linear trapezoidal rule
8. 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 [ Time Frame: 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 ]
   t1/2: Terminal half-life, calculated as λn/(ln 2)
9. 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 [ Time Frame: 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 ]
   CL/F: Apparent oral clearance, calculated as Dose/AUC0-inf
10. 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 [ Time Frame: 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 ]
    V/F: Apparent volume of distribution, calculated as Dose/(AUC0-inf * λn)
11. 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 [ Time Frame: 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 ]
    Cmax: Maximum plasma concentration; the highest concentration observed during a dosage interval
12. 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 [ Time Frame: 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 ]
    Tmax: The time at which Cmax was observed
13. 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 [ Time Frame: 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 ]
    Clast: Minimum plasma concentration; the last concentration observed during a dosage interval
14. 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 [ Time Frame: 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 ]
    Tlast: The time at which Clast was observed
15. 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 [ Time Frame: 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 ]
    AUC0-t: Area under the concentration versus time curve from time 0 to the last measured concentration (Clast) calculated by linear trapezoidal rule
16. 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 [ Time Frame: 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 ]
    AUC0-inf: Area under the concentration versus time curve from time 0 to infinity, calculated as AUC0-t + Clast/λn
17. 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 [ Time Frame: 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 ]
    AUC0-24: Area under the concentration versus time curve from time 0 to 24 hours calculated by linear trapezoidal rule
18. 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 [ Time Frame: 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 ]
    t1/2: Terminal half-life, calculated as λn/(ln 2)
19. 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 [ Time Frame: 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 ]
    Cmax: Maximum plasma concentration; the highest concentration observed during a dosage interval
20. 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 [ Time Frame: 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 ]
    Tmax: The time at which Cmax was observed
21. 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 [ Time Frame: 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 ]
    Clast: Minimum plasma concentration; the last concentration observed during a dosage interval
22. 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 [ Time Frame: 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 ]
    Tlast: The time at which Clast was observed
23. 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 [ Time Frame: 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 ]
    AUC0-t: Area under the concentration versus time curve from time 0 to the last measured concentration (Clast) calculated by linear trapezoidal rule
24. 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 [ Time Frame: 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 ]
    AUC0-inf: Area under the concentration versus time curve from time 0 to infinity, calculated as AUC0-t + Clast/λn
25. 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 [ Time Frame: 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 ]
    AUC0-24: Area under the concentration versus time curve from time 0 to 24 hours calculated by linear trapezoidal rule
26. 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 [ Time Frame: 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 ]
    t1/2: Terminal half-life, calculated as λn/(ln 2)
27. 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 [ Time Frame: 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 ]
    CL/F: Apparent oral clearance, calculated as Dose/AUC0-inf
28. 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 [ Time Frame: 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 ]
    V/F: Apparent volume of distribution, calculated as Dose/(AUC0-inf * λn)
29. 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 [ Time Frame: 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 ]
    Cmax: Maximum plasma concentration; the highest concentration observed during a dosage interval
30. 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 [ Time Frame: 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 ]
    Tmax: The time at which Cmax was observed
31. 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 [ Time Frame: 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 ]
    Clast: Minimum plasma concentration; the last concentration observed during a dosage interval
32. 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 [ Time Frame: 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 ]
    Tlast: The time at which Clast was observed
33. 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 [ Time Frame: 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 ]
    AUC0-t: Area under the concentration versus time curve from time 0 to the last measured concentration (Clast) calculated by linear trapezoidal rule
34. 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 [ Time Frame: 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 ]
    AUC0-inf: Area under the concentration versus time curve from time 0 to infinity, calculated as AUC0-t + Clast/λn
35. 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 [ Time Frame: 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 ]
    AUC0-24: Area under the concentration versus time curve from time 0 to 24 hours calculated by linear trapezoidal rule
36. 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 [ Time Frame: 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 ]
    t1/2: Terminal half-life, calculated as λn/(ln 2)

Eligibility Criteria

• Ages Eligible for Study: up to 12 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. 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
2. Subjects must be at least 10 kg and BMI ≤30
3. 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
4. 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
5. 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)
6. Able to provide pain assessment evaluations using an age-appropriate instrument provided in the protocol
7. 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)
8. Demonstrated the ability to tolerate clear fluids following surgery according to the SOC at each institution
9. Informed of the nature of the study and written informed consent has been obtained from the legally responsible parent(s)/legal guardian(s)
10. Provided assent in accordance with IRB requirements
11. Line in place for blood sampling

Exclusion Criteria:

1. Known allergies or sensitivities to oxymorphone or other opioid analgesics
2. Known sensitivity to any component of the study drug
3. Life expectancy <4 weeks
4. Positive pregnancy test at screening (females of reproductive age only)
5. Pregnant and/or lactating
6. Cyanotic heart disease
7. Respiratory, hepatic, renal, neurological, psychological disease, or any other clinically significant condition that would, in the Investigator's opinion, preclude participation in the study
8. Preoperative opioids administered for a period of more than 72 hours in duration
9. Abdominal trauma that would interfere with absorption of study drug
10. Increased intracranial pressure
11. Respiratory condition requiring intubation
12. History of uncontrolled seizures that are not being managed with anticonvulsants
13. Significant prior history of substance abuse or alcohol abuse
14. 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
15. Received a monoamine oxidase inhibitor (MAOI) within 14 days prior to the start of study drug
16. Received oxycodone or oxymorphone within 48 hours prior to study start
17. Investigator anticipates that the subject and/or parent(s)/legal guardian(s) would be unable to comply with the protocol
18. Subject (and/or parent[s]/legal guardian[s]) is(are) unable to communicate effectively with study personnel at an age-appropriate level

Contacts and Locations

Locations

United States, Arizona

Endo Clinical Trial Site #19

Tucson, Arizona, United States, 85724

United States, Arkansas

Endo Clinical Trial Site #1

Little Rock, Arkansas, United States, 72202

United States, Colorado

Endo Clinical Trial Site #3

Aurora, Colorado, United States, 80045

United States, Indiana

Endo Clinical Trial Site #6

Indianapolis, Indiana, United States, 46202

United States, Oklahoma

Endo Clinical Trial Site #11

Oklahoma City, Oklahoma, United States, 73104

United States, Pennsylvania

Endo Clinical Trial Site #12

Pittsburgh, Pennsylvania, United States, 15224

United States, Tennessee

Endo Clinical Trial Site #13

Nashville, Tennessee, United States, 37232

United States, Texas

Endo Clinical Trial Site #14

Dallas, Texas, United States, 75235

Sponsors and Collaborators

Endo Pharmaceuticals

  Study Documents (Full-Text)

Documents provided by Endo Pharmaceuticals:

Study Protocol and Statistical Analysis Plan  [PDF] August 21, 2013

More Information

• Responsible Party: Endo Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01210352
• Other Study ID Numbers: EN3319-302
• First Posted: September 28, 2010
• Results First Posted: May 7, 2019
• Last Update Posted: May 7, 2019
• Last Verified: May 2019

Keywords provided by Endo Pharmaceuticals:

surgical pain; acute pain; Acute Post Surgical Pain

Additional relevant MeSH terms:

Pain, Postoperative; Postoperative Complications; Pathologic Processes; Pain; Neurologic Manifestations; Oxymorphone; Analgesics, Opioid; Narcotics; Central Nervous System Depressants; Physiological Effects of Drugs; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Adjuvants, Anesthesia