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

Phase 4

Completed

Brief Summary: 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.

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.

Recruitment & Eligibility

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.

Arm && Interventions

Primary Outcome Measures

Name	Time	Method
Population Pharmacokinetic/Pharmacodynamic (PK/PD) Model for Hydromorphone: Clearance (Cl)	A maximum of 9 oral hydromorphone doses with potentially up to 54 hours duration.	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

Name	Time	Method
Mean (SE) of Faces, Legs Activity, Cry, Consolability (FLACC) Pain Scores on Hydromorphone Alone (Oral/Supplemental) Over Time [Ages >=28 Days to <5 Years]	Immediately prior to first oral dose, up to 54 hours	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	Immediately prior to first oral dose with potentially up to 54 hours duration.	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	Immediately prior to first oral dose, up to 54 hours	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.

Locations (14): Children's Hospital Medical Center of Akron
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Akron, Ohio, United States
Children's Hospital of Orange County - Pediatric Subspecialty
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Orange, California, United States
Stanford University Medical Center
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Stanford, California, United States
The Children's Hospital
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Aurora, Colorado, United States
Yale-New Haven Children's Hospital
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New Haven, Connecticut, United States
University of Iowa Hospitals and Clinics
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Iowa City, Iowa, United States
The University of North Carolina - CH
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Chapel Hill, North Carolina, United States
Saint Louis University - Department of Neurology and Psychiatry
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St. Louis, Missouri, United States
Children's Medical Center
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Dallas, Texas, United States
The University of Texas, Health Sciences Center at Houston
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Houston, Texas, United States
Texas Children's Hospital / Baylor College of Medicine
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Houston, Texas, United States
Jackson Memorial Hospital
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Miami, Florida, United States
Duke University Medical Center
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Durham, North Carolina, United States
Arkansas Children's Hospital
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Little Rock, Arkansas, United States