An Open-label Study of Hydromorphone Oral Solution in Subjects Aged 28 Days to 16 Years for Postoperative Pain (Palladone)

A Multi-center, Open-label, Dose Titration Study Pharmacokinetics/Pharmacodynamics, Safety, and Efficacy of Hydromorphone Oral Solution in Subjects From 28 Days to 16 Years of Age, Who Require Opioid Analgesics for Postoperative Pain

The primary objective of this study is to characterize the pharmacokinetics and pharmacodynamics of hydromorphone oral solution in pediatric subjects aged 28 days to 16 years inclusive. The secondary objectives are to characterize the safety and efficacy of hydromorphone oral solution in pediatric subjects aged 28 days to 16 years inclusive.

Study Overview

• Status: Completed
• Conditions: Postoperative Pain
• Intervention / Treatment: Drug: Hydromorphone

Detailed Description

Hydromorphone is an opioid analgesic that has been used for decades as an alternative to morphine in the treatment of moderate to severe malignant and nonmalignant pain. Only a small number of analgesics have been studied in children. The benefits to the subjects include contribution of knowledge that will provide for appropriate dosing regimen recommendations for future pediatric subjects.

Treatment consisted of both parenteral and oral hydromorphone. For up to 48 hours immediately following surgery, subjects were administered hydromorphone by IV PCA pump. Dosing with the oral hydromorphone HCl began when the subject was ready to take clear oral liquid. Subjects were administered oral hydromorphone HCl every 6 hours for up to 9 doses. The investigator determined the timing of the first dose based on each subject's clinical condition.

The duration of the treatment phase was up to 102 hours (up to 48 hours for the Parenteral Treatment Period and up to 54 hours for the Oral Treatment Period).

Efficacy was based on the oral hydromorphone treatment. Adverse events were collected for both the oral and parenteral treatments.

• Study Type: Interventional
• Enrollment (Actual): 116
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72202
      • Arkansas Children's Hospital
  • California
    • Orange, California, United States, 92868
      • Children's Hospital of Orange County - Pediatric Subspecialty
    • Stanford, California, United States, 94305
      • Stanford University Medical Center
  • Colorado
    • Aurora, Colorado, United States, 80218
      • The Children's Hospital
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale-New Haven Children's Hospital
  • Florida
    • Miami, Florida, United States, 33136
      • Jackson Memorial Hospital
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospitals and Clinics
  • Missouri
    • St. Louis, Missouri, United States, 63104
      • Saint Louis University - Department of Neurology and Psychiatry
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599-7221
      • The University of North Carolina - CH
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Ohio
    • Akron, Ohio, United States, 44308
      • Children's Hospital Medical Center of Akron
  • Texas
    • Dallas, Texas, United States, 75235
      • Children's Medical Center
    • Houston, Texas, United States, 77030
      • Texas Children's Hospital / Baylor College of Medicine
    • Houston, Texas, United States, 77030
      • The University of Texas, Health Sciences Center at Houston

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 weeks to 16 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Pediatric subjects aged 28 days to 16 years,
• Prospective subjects anticipated to have postoperative pain requiring oral opioid analgesics for at least 24 hours (up to 48 hours) following postoperative parenteral analgesia (up to 48 hours),
• Prospective subjects have received no more than a total of 7 doses of opioids in the 30 days prior to surgery.

Exclusion Criteria:

• Prospective subjects with clinically significant hepatic or renal dysfunction and impaired cardiac and/or respiratory reserve,
• Prospective subjects who have received opioid analgesic therapy other than hydromorphone or morphine sulfate during the up to 48-hour postoperative period prior to administration of first dose of oral hydromorphone,
• Prospective subjects who have received regional anesthetic blockade OR analgesic treatment with nonopioid medication within 6 hours prior to administration of first dose of oral hydromorphone.

Other protocol-specific inclusion/exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ≥ 28 Days to < 13 Months; infant and toddler	Drug: Hydromorphone; Oral hydromorphone solution dosed every 6 hours up to 9 doses. Dose is determined based on the expected weight range for each age group.; Other Names: Infants and todlers;; Young child;; Older child;; Adolescent.
Experimental: ≥ 13 months to < 5 years; young child	Drug: Hydromorphone; Oral hydromorphone solution dosed every 6 hours up to 9 doses. Dose is determined based on the expected weight range for each age group.; Other Names: Infants and todlers;; Young child;; Older child;; Adolescent.
Experimental: ≥ 5 years to < 12 years; older child	Drug: Hydromorphone; Oral hydromorphone solution dosed every 6 hours up to 9 doses. Dose is determined based on the expected weight range for each age group.; Other Names: Infants and todlers;; Young child;; Older child;; Adolescent.
Experimental: ≥ 12 years to < 17 years; adolescent	Drug: Hydromorphone; Oral hydromorphone solution dosed every 6 hours up to 9 doses. Dose is determined based on the expected weight range for each age group.; Other Names: Infants and todlers;; Young child;; Older child;; Adolescent.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Population Pharmacokinetic/Pharmacodynamic (PK/PD) Model for Hydromorphone: Clearance (Cl)	Model was built using sparse blood samples: Sampling times: immediately predose, and between 0.25-0.75, 1-3, and 4-6 hours postdose for the first 2 doses of oral hydromorphone: predose for each dose of oral hydromorphone HCl thereafter; and at the end of study. Efficacy was based on Oral treatment only.	A maximum of 9 oral hydromorphone doses with potentially up to 54 hours duration.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean (SE) of Faces, Legs Activity, Cry, Consolability (FLACC) Pain Scores on Hydromorphone Alone (Oral/Supplemental) Over Time [Ages >=28 Days to <5 Years]	There are 5 categories in this pediatric pain measurement: face, legs, activity, cry, and consolability. Responses in each category are scored between 0 and 2 (0 = normal, relaxed to 2 = upset, agitated), for a maximum total score of 10. The FLACC scale was used for children under the age of 3 years and older children who have limited verbal skills.	Immediately prior to first oral dose, up to 54 hours
Mean (SE) of Faces Pain Scale-Revised (FPS-R) [Ages >= 5 Years-< 12 Years] Pain Scores on Hydromorphone Alone (Oral/Supplemental)Over Time	Faces Pain Scale-Revised (FPS-R) consists of 6 facial expressions. Each face is 25 x 35 mm with 13 mm between faces. Each subject was asked to point to the face that reflected his or her pain. The end points are 0 = no pain and 10 = very much pain. The FPS-R scale was used for children over the age of 5 up to 12 years who have appropriate verbal skills.	Immediately prior to first oral dose with potentially up to 54 hours duration.
Mean (SE) of Visual Analog Scale (VAS) [Ages 12-16] Pain Scores on Hydromorphone Alone (Oral/Supplemental) Over Time	The Visual Analog Scale (VAS), a 10-cm Color Analog Scale anchored by the descriptors of 0 = "no pain" and 10 = "most pain," was used by children ≥ 12 years of age.	Immediately prior to first oral dose, up to 54 hours

Collaborators and Investigators

• Sponsor: Purdue Pharma LP
• Investigators: Principal Investigator: Gregory B. Hammer, MD, Stanford University

Study record dates

Study Major Dates

• Study Start: April 1, 2007
• Primary Completion (Actual): May 1, 2009
• Study Completion (Actual): April 1, 2010

Study Registration Dates

• First Submitted: April 24, 2007
• First Submitted That Met QC Criteria: April 24, 2007
• First Posted (Estimate): April 25, 2007

Study Record Updates

• Last Update Posted (Estimate): November 18, 2015
• Last Update Submitted That Met QC Criteria: October 19, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Keywords: opioid; pharmacokinetics; pharmacodynamics; Postoperative pain; Hydromorphone oral solution
• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Pain, Postoperative; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Hydromorphone
• Other Study ID Numbers: HMP4009