Use of Tapentadol Oral Solution for Pain After Surgery in Children From Newborn to Less Than 2 Years Old
Condition: Moderate to Severe Acute Postoperative Pain
MeSH terms: Pain, Postoperative
Intervention: Tapentadol
Intervention MeSH terms: Tapentadol
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 40.0
Sex: All
Minimum age: 1 Day
Maximum age: 23 Months
Healthy volunteers: No
Keywords: Post-surgical pain; Opioid

Summary:

      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.
    

Eligibility criteria:

        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.