A Multicenter, Open-Label, Safety and Pharmacokinetic Study of Oral Codeine Sulfate Administration in Pediatric Subjects 2 years old through 17 years old with Post-procedural Pain
This is a multicenter, open-label study to evaluate the safety and PK of oral codeine sulfate in pediatric subjects with mild to moderate post-procedural pain.
Eligible pediatric subjects will complete all screening procedures within 14 days before the scheduled procedure. Screening is permitted on the day of the procedure. At screening, the subject[Right Quote]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 IRB) before any protocol-specified procedures or assessments are performed.
Subjects may be inpatients, outpatient, 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 surgical center or six (6) hours after the last dose of oral codeine, whichever comes first.
On Day 0, local practice anesthesia will be established, after which subjects will undergo the scheduled procedure. Once subjects are able to tolerate oral medication after the procedure and, in the opinion of the investigator, the subject is experiencing mild to moderate pain, they will receive an initial dose of oral codeine sulfate. In order to receive study drug, subjects ≤7 years old must be assessed by the Faces, Legs, Activity, Cry, Consolability (FLACC) scale and have a score ≥1 and ≤6.The initial dose range of study drug will be based on the subjects[Right Quote] body weight. The calendar date and exact 24-hour clock time, dose, and formulation of oral codeine sulfate administered will be recorded.
Complete vital signs will be recorded after the subject has been in a sitting or resting position for 5 minutes at screening and, if screening was on a day prior to Day 0, will be repeated before the procedure on Day 0. In addition, a subset of vital signs will be measured immediately before administration of the study drug as well as at 30 minutes, 1 hour, and 2 hours after administration. Complete vital signs will also be measured immediately prior to discharge or 4 hours after the last dose of study drug, whichever occurs first.
To assess sedation/arousal, the University of Michigan Sedation Scale (UMSS) will be administered immediately before administration of study drug as well as at 30 minutes, 1 hour, and 2 hours after administration of study drug. The UMSS will also be measured immediately prior to discharge or 4 hours after the last dose of study drug prior to discharge, whichever occurs first.
Adverse events (AEs) will be monitored and recorded from the time parental permission/informed consent is obtained until discharge. The status of ongoing AEs at discharge and any serious adverse events (SAEs), which have occurred subsequent to discharge, will be gathered during the Day 30 +7 Follow-up Phone Call.
Pharmacokinetic blood samples will be collected from subjects at scheduled times per the study protocol.
If the child remains in the clinic setting and the investigator determines that additional dose(s) of codeine are indicated as part of the site[Right Quote]s standard of care, additional doses may be administered and the PK and safety assessments will continue according to the above schedule.
If the subject[Right Quote]s pain is not controlled by the study drug, rescue medication will be provided according to local practice although morphine and codeine should not be used as r
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
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.