Safety and Pharmacokinetic Study of Oral Morphine Sulfate in Pediatric Subjects
Condition: Pain
Intervention: Morphine Sulfate
Intervention MeSH terms: Morphine
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 50.0
Sex: All
Minimum age: 2 Years
Maximum age: 17 Years
Healthy volunteers: No

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.
    

Eligibility criteria:

        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.