Pharmacokinetics and Tolerability Study of Tapentadol for Postsurgical Pain in Children and Adolescents

This is a multicenter, open-label (all people involved know the identity of the
intervention), single-dose study to evaluate the pharmacokinetic (PK) profile (how drugs are
absorbed in the body, how they are distributed within the body and how they are removed from
the body over time), safety and tolerability of tapentadol 1 mg/kg oral solution (OS) in
children aged from 6 to less than 18 years after scheduled surgical procedures that
routinely produce acute, moderate to severe postsurgical pain. A screening phase, as per
standard of care but not exceeding 30 days, will include the preoperative evaluation, the
surgical procedure and its immediate post recovery, and will be followed by the open-label
treatment phase and end-of-study assessments. Study drug administration will take place
after the surgery has been completed, when the patient is alert, orientated, able to follow
commands and complete the required postoperative procedures, and able to tolerate fluid and
medication orally. Confinement to the study center for a patient will be as per standard of
care, and will include the surgery, the entire 15-hour postdose evaluation period and the
end-of-study evaluations. Children with a body weight less than 20 kg will be dosed with a
single dose of tapentadol 4 mg/mL OS and children with a body weight of 20 kg or greater
will be dosed with a single dose of tapentadol 20 mg/mL OS.

Inclusion Criteria:

- Parent(s) or the legal guardian(s) of the patient signed an informed consent document
indicating that they understand the purpose of the study, the risks and benefits of
the procedures required for the study and give permission for their child to
participate in the study

- Physical status rated as I or II on the American Society of Anesthesiologists (ASA)
rating scale

- Patient is alert, oriented, able to follow commands, able to understand the study
requirements and procedures, and able to communicate intelligibly with the health
care provider (taking into account his/her age)

- As per investigator's medical evaluation, patient is able to drink and tolerate oral
fluids and medication

- Patient has a postoperative pain intensity score >=4 on the McGrath Color Analog
Scale (CAS) as a result of a scheduled surgical procedure

Exclusion Criteria:

- History of seizure disorder or epilepsy, or serotonin syndrome, or mild or moderate
traumatic brain injury, stroke, transient ischemic attack, or brain neoplasm within 1
year of screening, or severe traumatic brain injury within 15 years of screening, or
any traumatic or hypoxic brain injury resulting in ongoing sequelae suggesting
transient changes in consciousness

- Moderate to severe renal or hepatic impairment

- Requires concomitant use of sedatives, other than those used during surgery

- Has received dextromethorphan within 2 days before the scheduled study drug
administration.