CompletedNCT00465647PalladoneUpdated Nov 18, 2015Results posted

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

A Phase 4 interventional study of Hydromorphone in Postoperative Pain, sponsored by Purdue Pharma LP. Completed at 14 sites in United States. Open to participants aged 28 Days to 16 Years. Per ClinicalTrials.gov, last updated 2015-11-18.

Sponsored by Purdue Pharma LP · Phase 4, Interventional, and Treatment

Phase: Phase 4
Study type: Interventional
Enrollment: 116
Allocation: Non-randomized
Ages: 28 Days to 16 Years
Sex: All

Study 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.

Read the 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.

Conditions studied

Postoperative Pain

Browse trials for

Pain, Postoperative 5,089

Keywords

Postoperative pain
Hydromorphone oral solution
opioid
pharmacokinetics
pharmacodynamics

In context

Pain, Postoperative

5,089 studies on the registry are indexed under Pain, Postoperative; 1,137 are open to participants now.

This study's enrollment of 116 is above the median of 75 across 4,341 interventional studies indexed under Pain, Postoperative.

Browse Pain, Postoperative studies →

Lead sponsor

Purdue Pharma LP is the lead sponsor of 58 studies on the registry; none are open to participants now.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 28 Days to 16 Years
Sexes eligible: All
Accepts healthy volunteers: No

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

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 design

Phase: Phase 4
Primary purpose: Treatment
Allocation: Non-randomized
Intervention model: Single group
Masking: None (open label)
Enrollment: 116 participants (actual)

Study arms

Experimental
≥ 28 Days to < 13 Months
infant and toddler
Drug: Hydromorphone
Experimental
≥ 13 months to < 5 years
young child
Drug: Hydromorphone
Experimental
≥ 5 years to < 12 years
older child
Drug: Hydromorphone
Experimental
≥ 12 years to < 17 years
adolescent
Drug: Hydromorphone

Interventions

DrugHydromorphone
Oral hydromorphone solution dosed every 6 hours up to 9 doses. Dose is determined based on the expected weight range for each age group.
Also known as: Infants and todlers;, Young child;, Older child;, Adolescent.

What researchers measure

Primary outcomes

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.
Time frame: A maximum of 9 oral hydromorphone doses with potentially up to 54 hours duration.

Secondary outcomes

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.
Time frame: 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.
Time frame: 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.
Time frame: Immediately prior to first oral dose, up to 54 hours

Results

Posted Mar 11, 2011

Participant flow

23-Apr-2007 (first subject, first visit) to 03-May-2009 (last subject, last visit). Multicenter study conducted at 18 sites in the United States (US).

Participant flow — Overall Study
Milestone	≥ 28 Days to < 13 Months	≥ 13 Months to < 5 Years	≥ 5 Years to <12 Years	≥ 12 Years to < 17 Years
Started	39	23	29	25
Completed	26	15	18	12
Not completed	13	8	11	13
Withdrew: Administrative	2	2	3	2
Withdrew: Adverse event	2	0	3	2
Withdrew: Withdrawal by subject	1	2	2	7
Withdrew: The "other" reasons included loss of iv	8	4	3	2

Outcome measures

PrimaryPopulation 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.

Time frame:: A maximum of 9 oral hydromorphone doses with potentially up to 54 hours duration.
Reported as:: Number · L/hour

Population Pharmacokinetic/Pharmacodynamic (PK/PD) Model for Hydromorphone: Clearance (Cl)
L/hour	All Patients
Population Pharmacokinetic/Pharmacodynamic (PK/PD) Model for Hydromorphone: Clearance (Cl)	114 (80.6 to 203)

SecondaryMean (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.

Time frame:: Immediately prior to first oral dose, up to 54 hours
Reported as:: Mean · units on a scale

Mean (SE) of Faces, Legs Activity, Cry, Consolability (FLACC) Pain Scores on Hydromorphone Alone (Oral/Supplemental) Over Time [Ages >=28 Days to <5 Years]
units on a scale	Oral ≥ 28 Days to < 13 Months	Oral ≥ 13 Months to < 5 Years	Oral ≥ 5 Years to < 12 Years	Oral ≥ 12 Years to < 17 Years
Predose	1.34 ± 0.388	2.67 ± 0.558	2.71 ± 0.522	—
Dose 1 (1 hour postdose)	1.13 ± 0.335	1.07 ± 0.483	2.17 ± 0.872	—
Dose 2 (1 hour postdose)	0.57 ± 0.223	0.67 ± 0.333	1.20 ± 0.583	—
Dose 3 (1 hour postdose)	0.27 ± 0.117	0.93 ± 0.715	0.75 ± 0.750	—
Dose 4 (1 hour postdose)	0.55 ± 0.274	0.85 ± 0.608	0.40 ± 0.400	—
Dose 5 (1 hour postdose)	0.70 ± 0.333	0.09 ± 0.091	1.00 ± 0.577	—
Dose 6 (1 hour postdose)	0.61 ± 0.465	1.20 ± 0.854	0.75 ± 0.479	—

SecondaryMean (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.

Time frame:: Immediately prior to first oral dose with potentially up to 54 hours duration.
Reported as:: Mean · units on a scale

Mean (SE) of Faces Pain Scale-Revised (FPS-R) [Ages >= 5 Years-< 12 Years] Pain Scores on Hydromorphone Alone (Oral/Supplemental)Over Time
units on a scale	Oral ≥ 28 Days to < 13 Months	Oral ≥ 13 Months to < 5 Years	Oral ≥ 5 Years to <12 Years	Oral ≥ 12 Years to < 17 Years
Predose	—	1.50 ± 0.957	2.59 ± 0.446	—
Dose 1 (1 hour postdose)	—	1.20 ± 1.200	2.25 ± 0.772	—
Dose 2 (1 hour postdose)	—	1.33 ± 1.333	0.92 ± 0.431	—
Dose 3 (1 hour postdose)	—	2.67 ± 0.667	1.54 ± 0.514	—
Dose 4 (1 hour postdose)	—	0 ± 0	1.86 ± 0.710	—
Dose 5 (1 hour postdose)	—	0 ± 0	1.64 ± 0.845	—
Dose 6 (1 hour postdose)	—	0 ± 0	0.40 ± 0.400	—

SecondaryMean (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.

Time frame:: Immediately prior to first oral dose, up to 54 hours
Reported as:: Mean · unit on a scale

Mean (SE) of Visual Analog Scale (VAS) [Ages 12-16] Pain Scores on Hydromorphone Alone (Oral/Supplemental) Over Time
unit on a scale	Oral ≥ 28 Days to < 13 Months	Oral ≥ 13 Months to < 5 Years	Oral ≥ 5 Years to <12 Years	Oral ≥ 12 Years to < 17 Years
Predose	—	—	—	4.04 ± 0.530
Dose 1 (1 hour postdose)	—	—	—	3.73 ± 0.629
Dose 2 (1 hour postdose)	—	—	—	3.95 ± 0.673
Dose 3 (1 hour postdose)	—	—	—	4.09 ± 0.569
Dose 4 (1 hour postdose)	—	—	—	4.13 ± 0.599
Dose 5 (1 hour postdose)	—	—	—	4.19 ± 0.945
Dose 6 (1 hour postdose)	—	—	—	3.25 ± 0.998

Adverse events

Collected over AEs that were ongoing or were reported during the 7 days following the subject's last dose of study drug were followed until resolution or for 30 days. SAEs were followed until the event resolved or the sequelae stabilized.. Non-serious events are listed at a 4.50% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Oral ≥ 28 Days to < 13 Months	—	2/39 (5.1%)	21/39 (53.8%)
Oral ≥ 13 Months to < 5 Years	—	2/23 (8.7%)	14/23 (60.9%)
Oral ≥ 5 Years to <12 Years	—	1/29 (3.4%)	15/29 (51.7%)
Oral ≥ 12 Years to < 17 Years	—	0/25 (0%)	6/25 (24%)
Parenteral ≥ 28 Days to < 13 Months	—	3/39 (7.7%)	27/39 (69.2%)
Parenteral ≥ 13 Months to < 5 Years	—	0/23 (0%)	16/23 (69.6%)
Parenteral ≥ 5 Years to < 12 Years	—	1/29 (3.4%)	19/29 (65.5%)
Parenteral ≥ 12 Years to < 17 Years	—	1/25 (4%)	17/25 (68%)

Most frequent serious events

Showing 10 of 12

Most frequent serious events
Event	Oral ≥ 28 Days to < 13 Months	Oral ≥ 13 Months to < 5 Years	Oral ≥ 5 Years to <12 Years	Oral ≥ 12 Years to < 17 Years	Parenteral ≥ 28 Days to < 13 Months	Parenteral ≥ 13 Months to < 5 Years	Parenteral ≥ 5 Years to < 12 Years	Parenteral ≥ 12 Years to < 17 Years
ChylothoraxRespiratory, thoracic and mediastinal disorders	0/39	2/23	0/29	0/25	0/39	0/23	0/29	0/25
Hypovolaemic shockVascular disorders	0/39	0/23	0/29	0/25	0/39	0/23	0/29	1/25
Disseminated intravascular coagulationBlood and lymphatic system disorders	0/39	0/23	1/29	0/25	0/39	0/23	0/29	0/25
Vascular procedure complication - DEATHInjury, poisoning and procedural complications	0/39	0/23	1/29	0/25	0/39	0/23	0/29	0/25
Acute respiratory failureRespiratory, thoracic and mediastinal disorders	0/39	0/23	0/29	0/25	0/39	0/23	1/29	0/25
Pericardial effusion - DEATHCardiac disorders	1/39	0/23	0/29	0/25	0/39	0/23	0/29	0/25
Laryngeal oedemaRespiratory, thoracic and mediastinal disorders	1/39	0/23	0/29	0/25	0/39	0/23	0/29	0/25
Streptococcus pneumoniaInfections and infestations	0/39	0/23	0/29	0/25	1/39	0/23	0/29	0/25
AtelectasisRespiratory, thoracic and mediastinal disorders	0/39	0/23	0/29	0/25	1/39	0/23	0/29	0/25
PneumothoraxRespiratory, thoracic and mediastinal disorders	0/39	0/23	0/29	0/25	1/39	0/23	0/29	0/25

Most frequent other events

Showing 10 of 32

Most frequent other events
Event	Oral ≥ 28 Days to < 13 Months	Oral ≥ 13 Months to < 5 Years	Oral ≥ 5 Years to <12 Years	Oral ≥ 12 Years to < 17 Years	Parenteral ≥ 28 Days to < 13 Months	Parenteral ≥ 13 Months to < 5 Years	Parenteral ≥ 5 Years to < 12 Years	Parenteral ≥ 12 Years to < 17 Years
NauseaGastrointestinal disorders	2/39	1/23	2/29	1/25	1/39	2/23	4/29	11/25
PruritusSkin and subcutaneous tissue disorders	3/39	3/23	4/29	1/25	10/39	5/23	6/29	8/25
Respiratory depressionRespiratory, thoracic and mediastinal disorders	12/39	4/23	0/29	2/25	5/39	1/23	0/29	0/25
AnxietyPsychiatric disorders	1/39	1/23	1/29	1/25	11/39	4/23	2/29	0/25
PyrexiaGeneral disorders	2/39	3/23	4/29	1/25	9/39	6/23	4/29	5/25
StridorRespiratory, thoracic and mediastinal disorders	0/39	0/23	0/29	0/25	8/39	3/23	0/29	0/25
VomitingGastrointestinal disorders	2/39	3/23	1/29	3/25	0/39	2/23	3/29	4/25
ConstipationGastrointestinal disorders	6/39	1/23	1/29	1/25	0/39	0/23	0/29	1/25
PneumothoraxRespiratory, thoracic and mediastinal disorders	1/39	1/23	4/29	1/25	2/39	1/23	0/29	0/25
AtelectasisRespiratory, thoracic and mediastinal disorders	1/39	3/23	2/29	0/25	4/39	3/23	3/29	1/25

Baseline characteristics

Age, Continuous
Age, Continuous(months)	≥ 28 Days to < 13 Months	≥ 13 Months to < 5 Years	≥ 5 Years to < 12 Years	≥ 12 Years to < 17 Years	Total
Mean	5.9 ± 2.76	33.6 ± 14.90	105.9 ± 27.06	178.3 ± 17.05	73.5 ± 69.32

Sex: Female, Male
Sex: Female, Male(Participants)	≥ 28 Days to < 13 Months	≥ 13 Months to < 5 Years	≥ 5 Years to < 12 Years	≥ 12 Years to < 17 Years	Total
Female	18	10	14	18	60
Male	21	13	15	7	56

Race/Ethnicity, Customized
Race/Ethnicity, Customized(participants)	≥ 28 Days to < 13 Months	≥ 13 Months to < 5 Years	≥ 5 Years to < 12 Years	≥ 12 Years to < 17 Years	Total
Asian	5	3	1	0	9
Native Hawaiian or Other Pacific Islander	0	1	0	0	1
Black or African American	6	2	10	5	23
White	28	16	18	20	82
Unknown or Not Reported	0	1	0	0	1

Study locations

14 sites

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

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Nov 18, 2015, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT00465647
Lead sponsor: Purdue Pharma LP
Responsible party: Sponsor
First posted: Apr 25, 2007
Start date: Apr 2007
Primary completion: May 2009
Completion: Apr 2010
Results posted: Mar 11, 2011
Last update: Nov 18, 2015

Study contacts

Gregory B. Hammer, MD

principal investigator · Stanford University

Oversight

Data monitoring committee: Yes

View the source record on ClinicalTrials.gov ↗

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