This is a multicenter, open-label (all people involved know the identity of the intervention), single dose trial to evaluate the pharmacokinetic (PK) profile (how drugs are absorbed in the body, how are they distributed within the body and how are they removed from the body over time) in children aged from birth to less than 2 years after a surgical procedure that routinely produces moderate to severe acute post-surgical pain.

The trial will also evaluate the safety and tolerability of tapentadol oral solution in the population studied and the effect of tapentadol oral solution on pain.

This clinical trial has 3 phases: enrollment, treatment (15 hours) and follow up.

During the enrolment phase consent and eligibility will be determined. After surgery, the participant will be given routine pain medication as per standard of care in the hospital.

Treatment phase: When the participant has a functioning gastrointestinal tract after surgery, can tolerate medication administered orally or via a feeding tube, meets the inclusion criteria, and does not meet any exclusion criterion, the participant will be allocated to the investigational medicinal product (IMP). Evaluations will be performed over the next 15 hours, including the assessment of the amount of pain. During this time, 2 blood samples will be taken for testing of the amount of tapentadol and its main metabolites in the participant's blood.

A final follow-up visit is planned to take place up to 2 weeks after taking the trial medication.

Inclusion Criteria:

• The participant's parent(s) or legal guardian(s) have given written informed consent to participate.
• Participant is not obese (e.g., a body weight above the 97th percentile for children based on the World Health Organization weight charts) with a minimum body weight of 2.5 kg.
• Physical status rated not higher than P3 on the American Society of Anesthesiologists physical status classification in participants aged from 1 month to less than 2 years.
• Participant has undergone surgery that, in the investigator's opinion, would reliably produce moderate to severe pain requiring opioid treatment.
• At the time of allocation to IMP, participant has a sedation score that is not higher than 2 (moderately sedated) on the University of Michigan Sedation Scale with the exception of participants who are mechanically ventilated in age subgroup 3, has a functioning gastrointestinal tract after surgery, and can tolerate medication administered orally or via a feeding tube at the time of allocation to IMP.
• Participant has a reliable venous vascular access for pharmacokinetic blood sampling.

Exclusion Criteria:

• The participant's parent(s) or legal guardian(s) is an employee of the investigator or trial site, with direct involvement in this trial or other trials under the direction of that investigator or trial site, or the participant, or participant's parent(s), or legal guardian(s) is a family member of the employees or the investigator.

• Participant has been previously exposed to tapentadol.

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

• Concomitant participation in another interventional clinical trial for the duration of this trial.

• Participant has undergone brain surgery.

• Participant has undergone a surgery that is expected to affect the absorption of tapentadol (e.g., to the gastrointestinal tract).

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

  • Seizure disorder.
  • Traumatic or hypoxic brain injury, i.e. brain contusion, stroke, transient ischemic attack, intracranial bleeding or hematoma, brain neoplasm.

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

  • Moderate to severe renal impairment.
  • Moderate to severe hepatic impairment, congestive hepatopathy, or hepatic portosystemic shunting.
  • Clinically relevant abnormal pulmonary function or clinically relevant respiratory disease that in the opinion of the investigator would put the participant at risk for developing respiratory depression, unless the participant is mechanically ventilated in age subgroup 3.

• Participant has signs or symptoms of congestive heart failure (e.g., requiring more than minimal inotropic support, an abnormal lactic acid value greater than 2-times upper limit of normal), or hemorrhagic disorder following surgery.

• Minimal inotropic medication is defined as:

  • Dopamine less or equal to 5 microgram/kg per minute.
  • Epinephrine less or equal to 0.03 microgram/kg per minute (but not both dopamine and epinephrine).
  • Milrinone less or equal to 0.5 microgram/kg per minute or less.

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

• Participant has cognitive or developmental impairment such that trial participation may affect or compromise the participant's safety, or the participant's ability to comply with the protocol requirements (as appropriate for the participant's age), in the investigator's judgment. Otherwise, participant's with cognitive or developmental impairment may be enrolled in the trial.

• Participant has a clinically relevant history of hypersensitivity, allergy, or contraindication to tapentadol (or ingredients).

• Participant has:

  • Clinically relevant abnormal 12-lead ECG in the investigator's judgment.
  • Signs of pre-excitation syndrome.
  • Corrected QT (QTcF) interval greater than 460 ms. Participant may be allocated to Investigational Medicinal Product with values greater than 460 ms if, in the investigator's opinion, the value is a consequence of cardiac surgery and is not considered clinically significant.

• Participant has clinically relevant abnormal lab values from a sample obtained postoperatively and prior to allocation to study medication. The following specifications will apply:

  • Aspartate transaminase or alanine transaminase is greater than 2.5-times upper limit of normal.
  • Total bilirubin is greater than 2-times upper limit of normal and direct bilirubin is greater than 20% of the total bilirubin, and for participants in age subgroup 3, the presence of pathological jaundice in the opinion of the investigator.
  • Glomerular filtration rate (calculated according to Schwartz et al. 1984):
  • less than 20 mL/min/1.73 m2 for participants less than 1 week old.
  • less than 30 mL/min/1.73 m2 for participants 1 week to 8 weeks old.
  • less than 50 mL/min/1.73 m2 for participants more than 8 weeks old.
  • Other parameters (in the investigator's judgment).

• Signs or symptoms indicative of a systemic infection within 24 hours prior to allocation to study medication.

• Participant has been administered a prohibited medication.

• The mother of a newborn or the breastfeeding mother of a participant was administered a prohibited medication.

• At the time of dosing, in the investigator's judgment, the participant has either of the following:

  • Clinically unstable upper or lower airway conditions or respiratory depression (unless the participant is mechanically ventilated in age subgroup 3).
  • Clinically unstable systolic or diastolic blood pressure, heart rate, or respiratory rate.

• Participant has a peripheral oxygen saturation (SpO2) <92% for acyanotic participant, or <75% for cyanotic participant, with or without supplemental oxygen via nasal cannula or high flow nasal cannula, at the time of allocation to Investigational Medicinal Product.

• For age subgroup 1 and age subgroup 2, participant requires continuous positive airway pressure or mechanical ventilation, at the time of allocation to Investigational Medicinal Product.

Information available on the Grünenthal Group Web Site (see URL below for details); according to the European Federation of Pharmaceutical Industries and Associations (EFPIA) Data Sharing Principles.