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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Purdue Pharma LP
ClinicalTrials.gov Identifier:
NCT00465647
First received: April 24, 2007
Last updated: January 24, 2012
Last verified: January 2012
  Purpose

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.


Condition Intervention Phase
Postoperative Pain
Drug: Hydromorphone
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Purdue Pharma LP:

Primary Outcome Measures:
  • Population Pharmacokinetic/Pharmacodynamic (PK/PD) Model for Hydromorphone: Clearance (Cl) [ Time Frame: A maximum of 9 oral hydromorphone doses with potentially up to 54 hours duration. ] [ Designated as safety issue: No ]

    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.



Secondary Outcome Measures:
  • Mean (SE) of Faces, Legs Activity, Cry, Consolability (FLACC) Pain Scores on Hydromorphone Alone (Oral/Supplemental) Over Time [Ages >=28 Days to <5 Years] [ Time Frame: Immediately prior to first oral dose, up to 54 hours ] [ Designated as safety issue: Yes ]
    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.

  • Mean (SE) of Faces Pain Scale-Revised (FPS-R) [Ages >= 5 Years-< 12 Years] Pain Scores on Hydromorphone Alone (Oral/Supplemental)Over Time [ Time Frame: Immediately prior to first oral dose with potentially up to 54 hours duration. ] [ Designated as safety issue: Yes ]
    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.

  • Mean (SE) of Visual Analog Scale (VAS) [Ages 12-16] Pain Scores on Hydromorphone Alone (Oral/Supplemental) Over Time [ Time Frame: Immediately prior to first oral dose, up to 54 hours ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 116
Study Start Date: April 2007
Study Completion Date: April 2010
Primary Completion Date: May 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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.

  Eligibility

Ages Eligible for Study:   up to 16 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00465647

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

No publications provided

Responsible Party: Purdue Pharma LP
ClinicalTrials.gov Identifier: NCT00465647     History of Changes
Other Study ID Numbers: HMP4009
Study First Received: April 24, 2007
Results First Received: December 22, 2010
Last Updated: January 24, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Purdue Pharma LP:
Postoperative pain
Hydromorphone oral solution
opioid
pharmacokinetics
pharmacodynamics

Additional relevant MeSH terms:
Pain, Postoperative
Postoperative Complications
Pathologic Processes
Pain
Signs and Symptoms
Pharmaceutical Solutions
Hydromorphone
Therapeutic Uses
Pharmacologic Actions
Analgesics, Opioid
Narcotics
Central Nervous System Depressants
Physiological Effects of Drugs
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on September 30, 2014