A Study of Oral Codeine Sulfate in Pediatric Patients With Post-procedural Pain

Eligible pediatric subjects will complete all screening procedures within 14 days before the
scheduled procedure. Screening will be permitted on the day of the procedure. At screening,
the subject's parent or guardian will provide written parental permission/informed consent to
participate in the study and subjects will provide assent (if required by the local
Institutional Review Board [IRB]) before any protocol-specified procedures or assessments are
performed.

Subjects may be inpatients, outpatients, or day-surgery patients at the study site who will
undergo procedures expected to result in at least mild to moderate post-procedure pain with
the day of the procedure noted as Day 0, and will be followed until discharge from the study
site.

Inclusion Criteria:

1. Has a parent or guardian providing written parental permission/informed consent, with
subject assent (if required by local IRB).

2. Is a child 2 years old through 17 years old, inclusive (at the time of informed
consent signing).

3. Has a routine pediatric procedure that is expected to cause at least mild to moderate
pain.

4. Is expected by the investigator to require a minimum of one (1) dose of oral codeine
for the treatment of mild to moderate post-procedural pain.

5. 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).

6. If female subject is of childbearing potential, she must have a negative urine or
serum pregnancy test result on the day of the scheduled procedure prior to the
procedure. In this population, female of childbearing potential is defined by the
onset of menarche, that is, menstruation, whether at irregular or regular intervals
(periods).

7. Must have vascular access to facilitate multiple blood draws.

Exclusion Criteria:

1. Is currently lactating.

2. 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.

3. Weighs less than 10.5 kg. (see Table 4 Maximum Number of Doses of Study Drug by Weight
for details)

4. Has weight ≤ 5th or ≥ 95th percentile for age based on CDC Growth Charts. (see
Appendix 6)

5. Has received codeine, hydrocodone, morphine or oxycodone in any form in the previous
seven (7) days.

6. Has used opioids chronically (e.g., codeine, morphine, oxycodone, hydrocodone, or
hydromorphone) for >7 calendar days within the previous 30 days before surgery.

7. Has known hypersensitivity or contraindication to receiving oral opioid(s).

8. Has an active enteral malabsorption disorder.

9. 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
conditions affecting the liver (e.g., chronic hepatitis) that may suggest the
potential for an increased susceptibility to hepatic toxicity with oral codeine
exposure. NOTE: Subjects with no previous history of liver function impairment may be
enrolled before results are available from screening laboratory samples.

10. 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 (1/3) of normal for the applicable age of this
study population. NOTE: Subjects with no previous history of kidney function
impairment may be enrolled before results are available from screening laboratory
samples.

11. Is undergoing a procedure as treatment for acute burns.

12. Has a history of substance abuse or there is evidence of current substance abuse, in
the investigator's opinion.

13. 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.