Safety and Pharmacokinetic Study of Oral Morphine Sulfate in Pediatric Subjects



Trial Phase

Phase 3

Trial Purpose and Description

Trial Purpose

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.

Participation Guidelines

2 Years - 17 Years

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

- 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.
Roxane Laboratories
April 2011
Last Updated:
April 2, 2012
Study HIC#:
1103008195 ID: NCT01322360