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Safety and Pharmacokinetic Study of Oral Morphine Sulfate in Pediatric Subjects

Phase 4
Completed
Conditions
Pain
Interventions
Registration Number
NCT01322360
Lead Sponsor
Roxane Laboratories
Brief Summary

The purpose of this study is to evaluate the tolerability and safety of oral morphine sulfate in the treatment of postoperative pain in different pediatric age groups following multiple-dose administration.

To determine multiple-dose pharmacokinetics (PK) of morphine sulfate in pediatric subjects.

To compare plasma concentration of morphine sulfate in each age group of pediatric subjects with adult plasma morphine sulfate concentrations.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
50
Inclusion Criteria
  • parent or guardian provided written parental permission/informed consent, with subject assent (if required by local IRB).
  • The child is 2 years old through 17 years old, inclusive (at the time of informed consent signing).
  • A routine pediatric procedure is expected to require inpatient hospitalization postoperatively.
  • Must be an inpatient for the study treatment period.
  • Is expected by the investigator to require use of oral opioid for the treatment of postoperative pain.
  • Has the ability to read and understand the study procedures and has the ability to communicate meaningfully with the study investigator and staff (if the subject is of preverbal age or cannot read or communicate meaningfully, then the subject's parent or guardian must meet this criterion).
  • Child is expected to experience moderate to severe postoperative pain, in the investigator's opinion, during the immediate postoperative period after discontinuation of intermittent administration of IV opioid (preferably morphine) and is able to tolerate oral medications.
  • If female subject is of childbearing potential, she must have a negative pregnancy test result at screening (serum) and on the day of surgery prior to surgery (urine).
  • Must have vascular access to facilitate blood draws.
Exclusion Criteria
  • Has significant medical disease(s), laboratory abnormalities, or conditions(s) that in the investigator's judgment could compromise the subject's welfare, ability to communicate with study staff, complete study activities, or would otherwise contraindicate study participation. There is no minimum value for SpO2 for inclusion in the study; this should be based on the investigator's judgment.
  • Has used opioids chronically (e.g., codeine, morphine, oxycodone, or hydromorphone, for >7 calendar days) within the previous 30 days.
  • Has known hypersensitivity or contraindication to receiving oral opioid(s).
  • Has a current active enteral malabsorption disorder.
  • Has impaired liver function (e.g., alanine aminotransferase [ALT] ≥3 times the upper limit of normal [ULN], or bilirubin ≥3 times ULN), known active hepatic disease (e.g., hepatitis), evidence of clinically significant chronic liver disease or other condition affecting the liver (e.g., chronic hepatitis) that may suggest the potential for an increased susceptibility to hepatic toxicity with oral morphine exposure. Subjects with no previous history of liver function impairment may be enrolled prior to receipt of screening laboratory testing results.
  • Has significantly impaired renal function or disease, as evidenced by an estimated glomerular filtration rate (i.e., from creatinine levels using the Schwartz formula) calculated to be less than one-third of normal for the applicable age of this study population. Subjects with no previous history of kidney function impairment may be enrolled prior to receipt of screening laboratory testing results.
  • Has a history of substance abuse or there is evidence of current substance abuse, in the investigator's opinion.
  • Has received epidural or regional anesthesia within 12 hours prior to the first dose of oral morphine sulfate.
  • Has participated in an interventional clinical study (investigational or marketed product) within 30 days before screening, or plans to participate in another clinical trial in the next 30 days.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Morphine SulfateMorphine Sulfateoral solution (10 mg/5 mL or 20 mg/5 mL) or tablets (15 mg or 30 mg)given based on based on the current pediatric prescribing guidelines
Primary Outcome Measures
NameTimeMethod
Number of Subjects Who Experienced Adverse Events That Led to Study DiscontinuationUp to 21 days

The primary safety endpoints were the percentage of subjects who experienced any AEs that led to study discontinuation, percentage of subjects with SAEs and those with a sedation score of 4. Secondary safety endpoints included the percentage of subjects who experienced any AEs of special interest, which included sedation, respiratory depression, nausea, vomiting, and pruritus of moderate to severe intensity/grade.

Additional secondary endpoints were the incidence, type, relationship to study drug, and severity of AEs, and the percentage of subjects with clinically significant decreases in SpO2 and respiratory rate, as assessed by the investigator.

Secondary Outcome Measures
NameTimeMethod
Number of Subjects Who Experienced Adverse Events of Moderate to Severe Intensity / GradeUp to 21 days

Subjects who experienced any AEs of special interest, which included sedation, respiratory depression, nausea, vomiting, and pruritus of moderate to severe intensity/grade

Trial Locations

Locations (11)

University of Texas Southwestern Medical Center

🇺🇸

Dallas, Texas, United States

Stanford University Medical Center

🇺🇸

Stanford, California, United States

University of Texas Health Science Center of Houston

🇺🇸

Houston, Texas, United States

Maricopa Integrated Health System

🇺🇸

Phoenix, Arizona, United States

Arkansas Children's Hospital

🇺🇸

Little Rock, Arkansas, United States

Yale New Haven Children's Hospital

🇺🇸

New Haven, Connecticut, United States

Children's Hospital of Michigan

🇺🇸

Detroit, Michigan, United States

Children's National Medical Center

🇺🇸

Washington, District of Columbia, United States

Children's Hospital Medical Center of Akron d/b/a Akron Children's Hospital

🇺🇸

Akron, Ohio, United States

Monroe Carell Jr. Children's Hospital at Vanderbilt

🇺🇸

Nashville, Tennessee, United States

Penn State Milton S. Hershey Medical Center

🇺🇸

Hershey, Pennsylvania, United States

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