A Study to Look at Tapentadol Oral Solution in Children and Adolescents in Pain

The supplemental opioid medication reflecting the standard of care will be available as
patient or nurse controlled intravenous morphine or hydromorphone. This supplemental opioid
medication will be given to control pain, as needed, in both the treatment and placebo
groups.

Children and adolescents 6 months and older will be dosed with a dose regimen of 1.25 mg/kg
for the first 24 hours of treatment. 24 hours after the start of study medication (and based
on clinical judgment) a dose reduction to 1.0 mg/kg is allowed.

Participants 30 days to less than 6 months old will be dosed with a regimen of 0.5 mg/kg for
the first 24 hours of treatment. The dose of study drug (IMP) may be reduced after 24 hours
(if there is a reduced need for analgesia according to the investigator's judgment) to 0.3
mg/kg.

Participants aged from birth to less than 30 days old will be dosed with a regimen of 0.1
mg/kg for the first 24 hours of treatment. The dose of study drug (IMP) may be reduced after
24 hours (if there is a reduced need for analgesia according to the investigator's judgment)
to 0.075 mg/kg.

A decision to maintain or alter the dose will depend on the effectiveness of the analgesia
(pain killer) and the adverse event profile observed in each participant over the first 24
hour dosing period.

In exceptional cases, if a participant has unbearable pain despite using nurse/patient
controlled analgesia (NCA/PCA), an additional bolus (defined as a clinician bolus) of
morphine or hydromorphone may be administered. The clinician bolus can be given either using
the NCA/PCA pump system or by an intravenous bolus injection. The opioid given as a clinician
bolus or if the NCA/PCA intravenous line fails must be the same as that used in the NCA/PCA
pump system.

Dosing with Investigational Medicinal Product will be stopped if:

- A switch to exclusively oral opioid analgesic medication is indicated according to the
local standard of care.

- Opioid analgesic medication is no longer needed.

- Investigational Medicinal Product has been administered for 72 hours. Safety evaluations
will include assessment of adverse events, vital signs, laboratory parameters,
electrocardiogram, and specific scale to assess suicidal ideation. The maximum study
duration for each participant will be 42 days.

Inclusion Criteria:

1. Informed consent, and if applicable assent, given according to local regulations.

2. Male or female participant aged from birth (37 weeks gestational age) to less than 18
years.

3. A female subject must be pre-menarchal, or surgically incapable of childbearing, or
sexually abstinent, or if a female subject is sexually active, then she must be
practicing an effective method of birth control (e.g., prescription hormonal
contraceptives, intra-uterine devices used according to the product's instruction,
double-barrier methods) before trial entry and throughout the trial.

4. A female subject must have a negative pregnancy test if aged 12 years or older, or is
post-menarchal, or is sexually active.

5. Participant has undergone surgery (other than brain surgery or gastrointestinal
surgery expected to affect the absorption of tapentadol [in the investigator's
judgment]) that, in the investigator's opinion, would reliably produce moderate to
severe pain requiring opioid treatment for at least 24 hours after first dose of
Investigational Medicinal Product. Participants must remain hospitalized until the End
of Treatment Visit.

6. Participant has received post-operative morphine or hydromorphone by NCA (Nurse
Controlled Analgesia)/PCA (Patient Controlled Analgesia), with or without a background
infusion of the same opioid, according to standard of care prior to
allocation/randomization to Investigational Medicinal Product and participant is
expected to require this morphine or hydromorphone by NCA/PCA after starting
Investigational Medicinal Product.

7. Participant is able to tolerate liquids at the time of allocation/randomization to
Investigational Medicinal Product.

Exclusion Criteria:

1. Participant, parent or the legal representative is an employee of the investigator or
trial site, with direct involvement in the proposed trial or other trials under the
direction of that investigator or trial site, or family member of the employees or the
investigator.

2. Participant has been previously exposed to tapentadol.

3. Participant has received an experimental drug or used an experimental medical device
within 28 days before allocation/randomization to IMP, or within a period less than 10
times the drug's half-life, whichever is longer.

4. Participant has a history or current condition of any one of the following:

- Non-febrile seizure disorder.

- Epilepsy.

- Serotonin syndrome.

- Traumatic or hypoxic brain injury, brain contusion, stroke, transient ischemic
attack, intracranial hematoma, post-traumatic amnesia, brain neoplasm, or
episode(s) of unconsciousness of more than 24 hours.

5. Participant has a history or current condition of any one of the following:

- Moderate to severe renal or hepatic impairment.

- Abnormal pulmonary function or clinically relevant respiratory disease (e.g.,
acute or severe bronchial asthma, hypercapnia).

6. Participant has a concomitant disease or disorder (e.g., endocrine, metabolic,
neurological, psychiatric, infection, febrile seizure, paralytic ileus) that in the
opinion of the investigator may affect or compromise participant safety during the
study participation.

7. Participant has history of suicidal ideation or behavior.

8. Participant is obese in the investigator's judgment. Obesity can be determined based
on appropriate BMI charts or tables; e.g., a BMI above the 97th percentile for
children based on the World Health Organization growth charts or the participant's
weight is less than 2500 gram.

9. Participant has a clinically relevant history of hypersensitivity, allergy, or
contraindication to the supplemental opioid analgesic medication or tapentadol, or the
excipients, or naloxone.

10. Participant is not able to understand and comply with the protocol as appropriate for
the age of the participant or participant is cognitively impaired in the
investigator's judgment such that they cannot comply with the protocol

11. Participant has a history of alcohol and/or substance abuse in the investigator's
judgment based on participant's history and physical examination.

12. Participant is taking prohibited concomitant medication.

13. Participant has received a long-acting opioid for the treatment of pain following
surgery within 6 hours of allocation/randomization to Investigational Medicinal
Product.

14. Participant has clinically relevant (in the investigator's judgment) abnormal values
for clinical chemistry or hematology (local laboratory sample taken after surgery).

- A participant is excluded if the:

- Aspartate transaminase or alanine transaminase is greater 3-times upper limit of
normal.

- Total bilirubin is greater 2-times upper limit of normal (except if the cause is
due to Gilbert's syndrome).

- Glomerular filtration rate less than 60 mL/min.

A subject aged from birth to less than 6 months old is excluded if:

- Aspartate transaminase or alanine transaminase is >3-times upper limit of normal.

- There is pathological jaundice in the opinion of the investigator.

- Glomerular filtration rate (calculated according to Schwartz et al. 1984) is:

- <20 mL/min/1.73 m2 for subjects <1 week postpartum.

- <30 mL/min/1.73 m2 for subjects 1 week to 8 weeks post-partum.

- <50 mL/min/1.73 m2 for subjects >8 weeks postpartum to <6 months old.

15. Participant has:

- Clinically relevant abnormal ECG.

- Signs of pre-excitation syndrome.

- Brugada's syndrome.

- QT or corrected QT interval (QTc) interval >470 ms for children aged 6 years to
less than 18 years old.

- QT or QTc interval >460 ms for children aged from birth to less than 6 years old.

16. Peri- or post-operative analgesia supplied by a continuous regional technique (e.g.,
nerve block, wound infiltration catheter) or subject controlled epidural analgesia
that was terminated less than 6 hours before allocation/randomization to
Investigational Medicinal Product.

17. Participant has post-operative clinically unstable systolic and diastolic blood
pressure, heart rate, respiratory depression, or clinically unstable upper or lower
airway conditions (in the investigator's judgment), or a saturation of peripheral
oxygen (SpO2) <92% at the time of randomization (allocation/randomization to
Investigational Medicinal Product).

18. Female participant is breast-feeding a child.

19. Participant requires continuous positive airway pressure or mechanical ventilation, at
the time of allocation to Investigational Medicinal Product.

20. The mother of a newborn subject or the breastfeeding mother of a subject was
administered a prohibited medication.