<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02221674</url>
  </required_header>
  <id_info>
    <org_study_id>KF5503-72</org_study_id>
    <secondary_id>2014-000623-24</secondary_id>
    <secondary_id>U1111-1153-1662</secondary_id>
    <secondary_id>R331333PAI2007</secondary_id>
    <nct_id>NCT02221674</nct_id>
  </id_info>
  <brief_title>Use of Tapentadol Oral Solution for Pain After Surgery in Children From Newborn to Less Than 2 Years Old</brief_title>
  <official_title>Open-label Evaluation of the Population Pharmacokinetic Profile, Safety, Tolerability, and Efficacy of Tapentadol Oral Solution for the Treatment of Post-surgical Pain in Children Aged From Birth to Less Than 2 Years</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Grünenthal GmbH</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Depomed</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Grünenthal GmbH</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a multicenter, open-label (all people involved know the identity of the&#xD;
      intervention), single dose trial to evaluate the pharmacokinetic (PK) profile (how drugs are&#xD;
      absorbed in the body, how are they distributed within the body and how are they removed from&#xD;
      the body over time) in children aged from birth to less than 2 years after a surgical&#xD;
      procedure that routinely produces moderate to severe acute post-surgical pain.&#xD;
&#xD;
      The trial will also evaluate the safety and tolerability of tapentadol oral solution in the&#xD;
      population studied and the effect of tapentadol oral solution on pain.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This clinical trial has 3 phases: enrollment, treatment (15 hours) and follow up.&#xD;
&#xD;
      During the enrolment phase consent and eligibility will be determined. After surgery, the&#xD;
      participant will be given routine pain medication as per standard of care in the hospital.&#xD;
&#xD;
      Treatment phase: When the participant has a functioning gastrointestinal tract after surgery,&#xD;
      can tolerate medication administered orally or via a feeding tube, meets the inclusion&#xD;
      criteria, and does not meet any exclusion criterion, the participant will be allocated to the&#xD;
      investigational medicinal product (IMP). Evaluations will be performed over the next 15&#xD;
      hours, including the assessment of the amount of pain. During this time, 2 blood samples will&#xD;
      be taken for testing of the amount of tapentadol and its main metabolites in the&#xD;
      participant's blood.&#xD;
&#xD;
      A final follow-up visit is planned to take place up to 2 weeks after taking the trial&#xD;
      medication.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <start_date type="Actual">November 5, 2014</start_date>
  <completion_date type="Actual">November 3, 2016</completion_date>
  <primary_completion_date type="Actual">October 14, 2016</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Pharmacokinetic Evaluation Based on Serum Concentrations of Tapentadol After a Single Dose of Tapentadol Oral Solution in Participants Aged 6 Months to Less Than 2 Years</measure>
    <time_frame>Up to 8 hours after IMP administration</time_frame>
    <description>The pharmacokinetic profile of Tapentadol and its major metabolite tapentadol-O-glucuronide was evaluated to enable data based recommendations for the use of Tapentadol in children of different ages.&#xD;
Each participant had a single pharmacokinetic sample taken at up to 2 different pre-defined time points.&#xD;
Serum was analyzed using liquid chromatography-tandem mass spectrometry. Mean and Standard Deviation of Serum Concentrations of Tapentadol were calculated.&#xD;
Summary statistics at a given time point were only determined if at least 2 participants had observations above the lower limit of quantification (LLOQ).&#xD;
If overall only a single sample was available at one of the pre-defined time points, the measured value is presented and the standard deviation is given as N/A.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetic Evaluation Based on Serum Concentrations of Tapentadol After a Single Dose of Tapentadol Oral Solution in Participants Aged 1 Month to Less Than 6 Months</measure>
    <time_frame>Up to 8 hours after IMP administration</time_frame>
    <description>The pharmacokinetic profile of Tapentadol and its major metabolite tapentadol-O-glucuronide was evaluated to enable data based recommendations for the use of Tapentadol in children of different ages.&#xD;
Each participant had a single pharmacokinetic sample taken at up to 2 different pre-defined time points.&#xD;
Serum was analyzed using liquid chromatography-tandem mass spectrometry. Mean and Standard Deviation of Serum Concentrations of Tapentadol were calculated.&#xD;
Summary statistics at a given time point were only determined if at least 2 participants had observations above the lower limit of quantification (LLOQ).&#xD;
If overall only a single sample was available at one of the pre-defined time points, the measured value is presented and the standard deviation is given as N/A.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetic Evaluation Based on Serum Concentrations of Tapentadol After a Single Dose of Tapentadol Oral Solution in Participants Aged From Birth to Less Than 1 Month</measure>
    <time_frame>Up to 8 hours after IMP</time_frame>
    <description>The pharmacokinetic profile of Tapentadol and its major metabolite tapentadol-O-glucuronide was evaluated to enable data based recommendations for the use of Tapentadol in children of different ages.&#xD;
Each participant had a single pharmacokinetic sample taken at up to 2 different pre-defined time points.&#xD;
Serum was analyzed using liquid chromatography-tandem mass spectrometry. Mean and Standard Deviation of Serum Concentrations of Tapentadol were calculated.&#xD;
Summary statistics at a given time point were only determined if at least 2 participants had observations above the lower limit of quantification (LLOQ).&#xD;
If overall only a single sample was available at one of the pre-defined time points, the measured value is presented and the standard deviation is given as N/A.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetic Profile of Serum Concentrations of Tapentadol-O-glucuronide After a Single Dose of Tapentadol Oral Solution in Participants Aged 6 Months to Less Than 2 Years</measure>
    <time_frame>Up to 8 hours after IMP</time_frame>
    <description>The pharmacokinetic profile of Tapentadol and its major metabolite tapentadol-O-glucuronide was evaluated to enable data based recommendations for the use of Tapentadol in children of different ages.&#xD;
Each participant had a single pharmacokinetic sample taken at up to 2 different pre-defined time points.&#xD;
Serum was analyzed using liquid chromatography-tandem mass spectrometry. Mean and Standard Deviation of Serum Concentrations of tapentadol-O-glucuronide were calculated.&#xD;
Summary statistics at a given time point were only determined if at least 2 participants had observations above the lower limit of quantification (LLOQ).&#xD;
If overall only a single sample was available at one of the pre-defined time points, the measured value is presented and the standard deviation is given as N/A.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetic Profile of Serum Concentrations of Tapentadol-O-glucuronide After a Single Dose of Tapentadol Oral Solution in Participants Aged 1 Month to Less Than 6 Months</measure>
    <time_frame>Up to 8 hours after IMP</time_frame>
    <description>The pharmacokinetic profile of Tapentadol and its major metabolite tapentadol-O-glucuronide was evaluated to enable data based recommendations for the use of Tapentadol in children of different ages.&#xD;
Each participant had a single pharmacokinetic sample taken at up to 2 different pre-defined time points.&#xD;
Serum was analyzed using liquid chromatography-tandem mass spectrometry. Mean and Standard Deviation of Serum Concentrations of tapentadol-O-glucuronide were calculated.&#xD;
Summary statistics at a given time point were only determined if at least 2 participants had observations above the lower limit of quantification (LLOQ).&#xD;
If overall only a single sample was available at one of the pre-defined time points, the measured value is presented and the standard deviation is given as N/A.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetic Profile of Serum Concentrations of Tapentadol-O-glucuronide After a Single Dose of Tapentadol Oral Solution in Participants Aged From Birth to Less Than 1 Month</measure>
    <time_frame>Up to 8 hours after IMP</time_frame>
    <description>The pharmacokinetic profile of Tapentadol and its major metabolite tapentadol-O-glucuronide was evaluated to enable data based recommendations for the use of Tapentadol in children of different ages.&#xD;
Each participant had a single pharmacokinetic sample taken at up to 2 different pre-defined time points.&#xD;
Serum was analyzed using liquid chromatography-tandem mass spectrometry. Mean and Standard Deviation of Serum Concentrations of tapentadol-O-glucuronide were calculated.&#xD;
Summary statistics at a given time point were only determined if at least 2 participants had observations above the lower limit of quantification (LLOQ).&#xD;
If overall only a single sample was available at one of the pre-defined time points, the measured value is presented and the standard deviation is given as N/A.</description>
  </primary_outcome>
  <other_outcome>
    <measure>Change From Baseline (Visit 1, After Surgery) in Pain Intensity</measure>
    <time_frame>Baseline; up to 15 hours after study medication</time_frame>
    <description>The change from baseline in pain intensity using the Face, Legs, Activity, Cry, Consolability Scale (FLACC Scale) at 15 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, 8 hours, 12 hours, and 15 hours after a single dose of tapentadol.&#xD;
The FLACC Scale is a behavioral scale for scoring postoperative pain in young children. It includes five categories of pain behaviors, including facial expression, leg movement, activity, cry, and consolability. The scale is scored in a range of 0-10 with 0 representing no pain.&#xD;
The pain intensity scores were summarized descriptively per scheduled time point.</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">40</enrollment>
  <condition>Moderate to Severe Acute Postoperative Pain</condition>
  <arm_group>
    <arm_group_label>Tapentadol</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Tapentadol 4 mg/mL immediate release oral solution, single dose post-operatively.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tapentadol</intervention_name>
    <arm_group_label>Tapentadol</arm_group_label>
    <other_name>Palexia®</other_name>
    <other_name>Nucynta®</other_name>
    <other_name>Yantil®</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  The participant's parent(s) or legal guardian(s) have given written informed consent&#xD;
             to participate.&#xD;
&#xD;
          -  Participant is not obese (e.g., a body weight above the 97th percentile for children&#xD;
             based on the World Health Organization weight charts) with a minimum body weight of&#xD;
             2.5 kg.&#xD;
&#xD;
          -  Physical status rated not higher than P3 on the American Society of Anesthesiologists&#xD;
             physical status classification in participants aged from 1 month to less than 2 years.&#xD;
&#xD;
          -  Participant has undergone surgery that, in the investigator's opinion, would reliably&#xD;
             produce moderate to severe pain requiring opioid treatment.&#xD;
&#xD;
          -  At the time of allocation to IMP, participant has a sedation score that is not higher&#xD;
             than 2 (moderately sedated) on the University of Michigan Sedation Scale with the&#xD;
             exception of participants who are mechanically ventilated in age subgroup 3, has a&#xD;
             functioning gastrointestinal tract after surgery, and can tolerate medication&#xD;
             administered orally or via a feeding tube at the time of allocation to IMP.&#xD;
&#xD;
          -  Participant has a reliable venous vascular access for pharmacokinetic blood sampling.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  The participant's parent(s) or legal guardian(s) is an employee of the investigator or&#xD;
             trial site, with direct involvement in this trial or other trials under the direction&#xD;
             of that investigator or trial site, or the participant, or participant's parent(s), or&#xD;
             legal guardian(s) is a family member of the employees or the investigator.&#xD;
&#xD;
          -  Participant has been previously exposed to tapentadol.&#xD;
&#xD;
          -  Participant has received an experimental drug or used an experimental medical device&#xD;
             within 28 days before allocation to study medication, or within a period less than 10&#xD;
             times the drug's half-life, whichever is longer.&#xD;
&#xD;
          -  Concomitant participation in another interventional clinical trial for the duration of&#xD;
             this trial.&#xD;
&#xD;
          -  Participant has undergone brain surgery.&#xD;
&#xD;
          -  Participant has undergone a surgery that is expected to affect the absorption of&#xD;
             tapentadol (e.g., to the gastrointestinal tract).&#xD;
&#xD;
          -  Participant has a history or current condition of any one of the following:&#xD;
&#xD;
               -  Seizure disorder.&#xD;
&#xD;
               -  Traumatic or hypoxic brain injury, i.e. brain contusion, stroke, transient&#xD;
                  ischemic attack, intracranial bleeding or hematoma, brain neoplasm.&#xD;
&#xD;
          -  Participant has a history or current condition of any one of the following:&#xD;
&#xD;
               -  Moderate to severe renal impairment.&#xD;
&#xD;
               -  Moderate to severe hepatic impairment, congestive hepatopathy, or hepatic&#xD;
                  portosystemic shunting.&#xD;
&#xD;
               -  Clinically relevant abnormal pulmonary function or clinically relevant&#xD;
                  respiratory disease that in the opinion of the investigator would put the&#xD;
                  participant at risk for developing respiratory depression, unless the participant&#xD;
                  is mechanically ventilated in age subgroup 3.&#xD;
&#xD;
          -  Participant has signs or symptoms of congestive heart failure (e.g., requiring more&#xD;
             than minimal inotropic support, an abnormal lactic acid value greater than 2-times&#xD;
             upper limit of normal), or hemorrhagic disorder following surgery.&#xD;
&#xD;
          -  Minimal inotropic medication is defined as:&#xD;
&#xD;
               -  Dopamine less or equal to 5 microgram/kg per minute.&#xD;
&#xD;
               -  Epinephrine less or equal to 0.03 microgram/kg per minute (but not both dopamine&#xD;
                  and epinephrine).&#xD;
&#xD;
               -  Milrinone less or equal to 0.5 microgram/kg per minute or less.&#xD;
&#xD;
          -  Participant has a concomitant disease or disorder (e.g., endocrine, metabolic,&#xD;
             neurological, or psychiatric disorder, or a febrile seizure or paralytic ileus) that&#xD;
             in the opinion of the investigator may affect or compromise participant's safety&#xD;
             during the trial participation.&#xD;
&#xD;
          -  Participant has cognitive or developmental impairment such that trial participation&#xD;
             may affect or compromise the participant's safety, or the participant's ability to&#xD;
             comply with the protocol requirements (as appropriate for the participant's age), in&#xD;
             the investigator's judgment. Otherwise, participant's with cognitive or developmental&#xD;
             impairment may be enrolled in the trial.&#xD;
&#xD;
          -  Participant has a clinically relevant history of hypersensitivity, allergy, or&#xD;
             contraindication to tapentadol (or ingredients).&#xD;
&#xD;
          -  Participant has:&#xD;
&#xD;
               -  Clinically relevant abnormal 12-lead ECG in the investigator's judgment.&#xD;
&#xD;
               -  Signs of pre-excitation syndrome.&#xD;
&#xD;
               -  Corrected QT (QTcF) interval greater than 460 ms. Participant may be allocated to&#xD;
                  Investigational Medicinal Product with values greater than 460 ms if, in the&#xD;
                  investigator's opinion, the value is a consequence of cardiac surgery and is not&#xD;
                  considered clinically significant.&#xD;
&#xD;
          -  Participant has clinically relevant abnormal lab values from a sample obtained&#xD;
             postoperatively and prior to allocation to study medication. The following&#xD;
             specifications will apply:&#xD;
&#xD;
               -  Aspartate transaminase or alanine transaminase is greater than 2.5-times upper&#xD;
                  limit of normal.&#xD;
&#xD;
               -  Total bilirubin is greater than 2-times upper limit of normal and direct&#xD;
                  bilirubin is greater than 20% of the total bilirubin, and for participants in age&#xD;
                  subgroup 3, the presence of pathological jaundice in the opinion of the&#xD;
                  investigator.&#xD;
&#xD;
               -  Glomerular filtration rate (calculated according to Schwartz et al. 1984):&#xD;
&#xD;
               -  less than 20 mL/min/1.73 m2 for participants less than 1 week old.&#xD;
&#xD;
               -  less than 30 mL/min/1.73 m2 for participants 1 week to 8 weeks old.&#xD;
&#xD;
               -  less than 50 mL/min/1.73 m2 for participants more than 8 weeks old.&#xD;
&#xD;
               -  Other parameters (in the investigator's judgment).&#xD;
&#xD;
          -  Signs or symptoms indicative of a systemic infection within 24 hours prior to&#xD;
             allocation to study medication.&#xD;
&#xD;
          -  Participant has been administered a prohibited medication.&#xD;
&#xD;
          -  The mother of a newborn or the breastfeeding mother of a participant was administered&#xD;
             a prohibited medication.&#xD;
&#xD;
          -  At the time of dosing, in the investigator's judgment, the participant has either of&#xD;
             the following:&#xD;
&#xD;
               -  Clinically unstable upper or lower airway conditions or respiratory depression&#xD;
                  (unless the participant is mechanically ventilated in age subgroup 3).&#xD;
&#xD;
               -  Clinically unstable systolic or diastolic blood pressure, heart rate, or&#xD;
                  respiratory rate.&#xD;
&#xD;
          -  Participant has a peripheral oxygen saturation (SpO2) &lt;92% for acyanotic participant,&#xD;
             or &lt;75% for cyanotic participant, with or without supplemental oxygen via nasal&#xD;
             cannula or high flow nasal cannula, at the time of allocation to Investigational&#xD;
             Medicinal Product.&#xD;
&#xD;
          -  For age subgroup 1 and age subgroup 2, participant requires continuous positive airway&#xD;
             pressure or mechanical ventilation, at the time of allocation to Investigational&#xD;
             Medicinal Product.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>1 Day</minimum_age>
    <maximum_age>23 Months</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Clinical Trial Director</last_name>
    <role>Study Director</role>
    <affiliation>Grünenthal GmbH</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>US001</name>
      <address>
        <city>Palo Alto</city>
        <state>California</state>
        <zip>94305</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>US002</name>
      <address>
        <city>Louisville</city>
        <state>Kentucky</state>
        <zip>40202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>US006</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27710</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>US004</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>PL004</name>
      <address>
        <city>Toruń</city>
        <zip>87-100</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>PL001</name>
      <address>
        <city>Łódź</city>
        <zip>93-338</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GB001</name>
      <address>
        <city>Sheffield</city>
        <zip>S10 2TH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Poland</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2018</verification_date>
  <study_first_submitted>August 19, 2014</study_first_submitted>
  <study_first_submitted_qc>August 19, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 20, 2014</study_first_posted>
  <results_first_submitted>August 22, 2017</results_first_submitted>
  <results_first_submitted_qc>November 8, 2017</results_first_submitted_qc>
  <results_first_posted type="Actual">December 12, 2017</results_first_posted>
  <last_update_submitted>January 3, 2018</last_update_submitted>
  <last_update_submitted_qc>January 3, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">January 29, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Post-surgical pain</keyword>
  <keyword>Opioid</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pain, Postoperative</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tapentadol</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>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.</ipd_description>
    <ipd_url>http://www.grunenthal.com/grt-web/Grunenthal_Group/Research_Development/Grunenthal_Clinical_Trials/Data_Sharing/296200025.jsp</ipd_url>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <recruitment_details>The first patient signed the informed consent on 05 Nov 2014. The last patient completed the trial on 03 Nov 2016. The trial followed a staggered recruitment by age, starting with the recruitment of patients in the oldest age group. Exposure and safety of at least 2 patients has been assessed before opening enrollment in the next younger age group.</recruitment_details>
      <pre_assignment_details>Consent was obtained for 40 participants in the trial. 19 participants were allocated and received study drug (investigational medicinal product). Pharmacokinetic data was obtained for 18 participants.&#xD;
21 patients were enrolled but not allocated.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Participants Aged 6 Months to Less Than 2 Years</title>
          <description>Infants aged 6 months to less than 2 years at the time of allocation to IMP (investigational medicinal product).&#xD;
Participants received a single dose of tapentadol oral solution postoperatively. The dose administered depended on the age of the subject and the body weight.&#xD;
Infants aged 6 months to less than 2 years received a dose of 0.75 mg/kg.</description>
        </group>
        <group group_id="P2">
          <title>Participants Aged 1 Month to Less Than 6 Months</title>
          <description>Infants aged 1 month to less than 6 months at the time of allocation to IMP. Participants received a single dose of tapentadol oral solution postoperatively. The dose administered depended on the age of the subject and the body weight.&#xD;
Infants aged 1 month to less than 6 months received a dose of 0.60 mg/kg.</description>
        </group>
        <group group_id="P3">
          <title>Participants Aged From Birth to Less Than 1 Month</title>
          <description>Neonates aged less than 1 month at the time of allocation to IMP (must be ≥37 weeks gestational age).&#xD;
Participants received a single dose of tapentadol oral solution postoperatively. The dose administered depended on the age of the subject and the body weight.&#xD;
Neonates aged less than 1 month received a dose of 0.50 mg/kg.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
                <participants group_id="P2" count="6"/>
                <participants group_id="P3" count="5"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
                <participants group_id="P2" count="6"/>
                <participants group_id="P3" count="5"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>The baseline analysis population is based on the participants allocated to IMP.</population>
      <group_list>
        <group group_id="B1">
          <title>Participants Aged 6 Months to Less Than 2 Years</title>
          <description>Infants aged 6 months to less than 2 years at the time of allocation to IMP. Participants received a single dose of tapentadol oral solution postoperatively. The dose administered depended on the age of the subject and the body weight.&#xD;
Infants aged 6 months to less than 2 years received a dose of 0.75 mg/kg.</description>
        </group>
        <group group_id="B2">
          <title>Participants Aged 1 Month to Less Than 6 Months</title>
          <description>Infants aged 1 month to less than 6 months at the time of allocation to IMP. Participants received a single dose of tapentadol oral solution postoperatively. The dose administered depended on the age of the subject and the body weight.&#xD;
Infants aged 1 month to less than 6 months received a dose of 0.60 mg/kg.</description>
        </group>
        <group group_id="B3">
          <title>Participants Aged From Birth to Less Than 1 Month</title>
          <description>Neonates aged less than 1 month at the time of allocation to IMP (must be ≥37 weeks gestational age).&#xD;
Participants received a single dose of tapentadol oral solution postoperatively. The dose administered depended on the age of the subject and the body weight.&#xD;
Neonates aged less than 1 month received a dose of 0.50 mg/kg.</description>
        </group>
        <group group_id="B4">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="8"/>
            <count group_id="B2" value="6"/>
            <count group_id="B3" value="5"/>
            <count group_id="B4" value="19"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="5"/>
                    <measurement group_id="B4" value="19"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>days</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="420.0" spread="147.8"/>
                    <measurement group_id="B2" value="92.8" spread="37.9"/>
                    <measurement group_id="B3" value="14.6" spread="8.5"/>
                    <measurement group_id="B4" value="210.0" spread="209.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Poland</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>United Kingdom</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Height</title>
          <units>centimeter</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="73.3" spread="5.2"/>
                    <measurement group_id="B2" value="62.0" spread="4.3"/>
                    <measurement group_id="B3" value="53.4" spread="4.4"/>
                    <measurement group_id="B4" value="64.5" spread="9.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Weight</title>
          <units>kilogram</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="9.21" spread="1.50"/>
                    <measurement group_id="B2" value="5.92" spread="1.18"/>
                    <measurement group_id="B3" value="3.78" spread="0.66"/>
                    <measurement group_id="B4" value="6.74" spread="2.59"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Body Mass Index (BMI)</title>
          <units>kilogram per square meter</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="17.11" spread="1.36"/>
                    <measurement group_id="B2" value="15.28" spread="1.31"/>
                    <measurement group_id="B3" value="13.36" spread="2.49"/>
                    <measurement group_id="B4" value="15.55" spread="2.24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Baseline Pain Intensity using the FLACC Scale</title>
          <description>Pain intensity using the Face, Legs, Activity, Cry, Consolability Scale (FLACC Scale) at baseline visit.&#xD;
The FLACC Scale is a behavioral scale for scoring postoperative pain in young children. It includes five categories of pain behaviors, including facial expression, leg movement, activity, cry, and consolability. The scale is scored in a range of 0-10 with 0 representing no pain.</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2.8" spread="2.9"/>
                    <measurement group_id="B2" value="3.8" spread="3.9"/>
                    <measurement group_id="B3" value="1.6" spread="1.5"/>
                    <measurement group_id="B4" value="2.8" spread="3.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Pharmacokinetic Evaluation Based on Serum Concentrations of Tapentadol After a Single Dose of Tapentadol Oral Solution in Participants Aged 6 Months to Less Than 2 Years</title>
        <description>The pharmacokinetic profile of Tapentadol and its major metabolite tapentadol-O-glucuronide was evaluated to enable data based recommendations for the use of Tapentadol in children of different ages.&#xD;
Each participant had a single pharmacokinetic sample taken at up to 2 different pre-defined time points.&#xD;
Serum was analyzed using liquid chromatography-tandem mass spectrometry. Mean and Standard Deviation of Serum Concentrations of Tapentadol were calculated.&#xD;
Summary statistics at a given time point were only determined if at least 2 participants had observations above the lower limit of quantification (LLOQ).&#xD;
If overall only a single sample was available at one of the pre-defined time points, the measured value is presented and the standard deviation is given as N/A.</description>
        <time_frame>Up to 8 hours after IMP administration</time_frame>
        <population>The trial used sparse sampling for the assessment of Pharmacokinetic. Overall, there were 6 time points for sampling. Participants were allocated to 2 different time points for a blood sample to be taken. Some participants only had one sample taken. Some samples were below the Lower limit of quantification (LLOQ).</population>
        <group_list>
          <group group_id="O1">
            <title>Participants Aged 6 Months to Less Than 2 Years - PK Set</title>
            <description>Infants aged 6 months to less than 2 years at the time of allocation to IMP who had quantifiable serum concentrations.</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetic Evaluation Based on Serum Concentrations of Tapentadol After a Single Dose of Tapentadol Oral Solution in Participants Aged 6 Months to Less Than 2 Years</title>
          <description>The pharmacokinetic profile of Tapentadol and its major metabolite tapentadol-O-glucuronide was evaluated to enable data based recommendations for the use of Tapentadol in children of different ages.&#xD;
Each participant had a single pharmacokinetic sample taken at up to 2 different pre-defined time points.&#xD;
Serum was analyzed using liquid chromatography-tandem mass spectrometry. Mean and Standard Deviation of Serum Concentrations of Tapentadol were calculated.&#xD;
Summary statistics at a given time point were only determined if at least 2 participants had observations above the lower limit of quantification (LLOQ).&#xD;
If overall only a single sample was available at one of the pre-defined time points, the measured value is presented and the standard deviation is given as N/A.</description>
          <population>The trial used sparse sampling for the assessment of Pharmacokinetic. Overall, there were 6 time points for sampling. Participants were allocated to 2 different time points for a blood sample to be taken. Some participants only had one sample taken. Some samples were below the Lower limit of quantification (LLOQ).</population>
          <units>nanogram per milliliter</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>30 minutes after administration</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.8" spread="5.21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>1 hour after administration</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18.79" spread="NA">One sample was used at this specified time point.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>2 hours after administration</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="32.2" spread="14.92"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>4 hours after administration</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.1" spread="5.97"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>6 hours after administration</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14.85" spread="NA">One sample was used at this specified time point.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>8 hours after administration</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.7" spread="4.15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Pharmacokinetic Evaluation Based on Serum Concentrations of Tapentadol After a Single Dose of Tapentadol Oral Solution in Participants Aged 1 Month to Less Than 6 Months</title>
        <description>The pharmacokinetic profile of Tapentadol and its major metabolite tapentadol-O-glucuronide was evaluated to enable data based recommendations for the use of Tapentadol in children of different ages.&#xD;
Each participant had a single pharmacokinetic sample taken at up to 2 different pre-defined time points.&#xD;
Serum was analyzed using liquid chromatography-tandem mass spectrometry. Mean and Standard Deviation of Serum Concentrations of Tapentadol were calculated.&#xD;
Summary statistics at a given time point were only determined if at least 2 participants had observations above the lower limit of quantification (LLOQ).&#xD;
If overall only a single sample was available at one of the pre-defined time points, the measured value is presented and the standard deviation is given as N/A.</description>
        <time_frame>Up to 8 hours after IMP administration</time_frame>
        <population>The trial used sparse sampling for the assessment of Pharmacokinetic. Overall, there were 6 time points for sampling. Participants were allocated to 2 different time points for a blood sample to be taken. Some participants only had one sample taken. Some samples were below the Lower limit of quantification (LLOQ).</population>
        <group_list>
          <group group_id="O1">
            <title>Participants Aged 1 Month to Less Than 6 Months - PK Set</title>
            <description>Infants aged 1 month to less than 6 months at the time of allocation to IMP who had quantifiable serum concentrations.</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetic Evaluation Based on Serum Concentrations of Tapentadol After a Single Dose of Tapentadol Oral Solution in Participants Aged 1 Month to Less Than 6 Months</title>
          <description>The pharmacokinetic profile of Tapentadol and its major metabolite tapentadol-O-glucuronide was evaluated to enable data based recommendations for the use of Tapentadol in children of different ages.&#xD;
Each participant had a single pharmacokinetic sample taken at up to 2 different pre-defined time points.&#xD;
Serum was analyzed using liquid chromatography-tandem mass spectrometry. Mean and Standard Deviation of Serum Concentrations of Tapentadol were calculated.&#xD;
Summary statistics at a given time point were only determined if at least 2 participants had observations above the lower limit of quantification (LLOQ).&#xD;
If overall only a single sample was available at one of the pre-defined time points, the measured value is presented and the standard deviation is given as N/A.</description>
          <population>The trial used sparse sampling for the assessment of Pharmacokinetic. Overall, there were 6 time points for sampling. Participants were allocated to 2 different time points for a blood sample to be taken. Some participants only had one sample taken. Some samples were below the Lower limit of quantification (LLOQ).</population>
          <units>nanogram per milliliter</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>30 minutes after administration</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.3" spread="6.30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>1 hour after administration</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="35.27" spread="NA">One sample was used at this specified time point.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>2 hours after administration</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="27.3" spread="0.81"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>4 hours after administration</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="25.9" spread="10.33"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>6 hours after administration</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="32.75" spread="NA">One sample was used at this specified time point.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>8 hours after administration</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.6" spread="1.81"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Pharmacokinetic Evaluation Based on Serum Concentrations of Tapentadol After a Single Dose of Tapentadol Oral Solution in Participants Aged From Birth to Less Than 1 Month</title>
        <description>The pharmacokinetic profile of Tapentadol and its major metabolite tapentadol-O-glucuronide was evaluated to enable data based recommendations for the use of Tapentadol in children of different ages.&#xD;
Each participant had a single pharmacokinetic sample taken at up to 2 different pre-defined time points.&#xD;
Serum was analyzed using liquid chromatography-tandem mass spectrometry. Mean and Standard Deviation of Serum Concentrations of Tapentadol were calculated.&#xD;
Summary statistics at a given time point were only determined if at least 2 participants had observations above the lower limit of quantification (LLOQ).&#xD;
If overall only a single sample was available at one of the pre-defined time points, the measured value is presented and the standard deviation is given as N/A.</description>
        <time_frame>Up to 8 hours after IMP</time_frame>
        <population>The trial used sparse sampling for the assessment of Pharmacokinetic. Overall, there were 6 time points for sampling. Participants were allocated to 2 different time points for a blood sample to be taken. Some participants only had one sample taken. Some samples were below the Lower limit of quantification (LLOQ).</population>
        <group_list>
          <group group_id="O1">
            <title>Participants Aged From Birth to Less Than 1 Month - PK Set</title>
            <description>Neonates aged less than 1 month (must be ≥37 weeks gestational age) at the time of allocation to IMP who had quantifiable serum concentrations.</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetic Evaluation Based on Serum Concentrations of Tapentadol After a Single Dose of Tapentadol Oral Solution in Participants Aged From Birth to Less Than 1 Month</title>
          <description>The pharmacokinetic profile of Tapentadol and its major metabolite tapentadol-O-glucuronide was evaluated to enable data based recommendations for the use of Tapentadol in children of different ages.&#xD;
Each participant had a single pharmacokinetic sample taken at up to 2 different pre-defined time points.&#xD;
Serum was analyzed using liquid chromatography-tandem mass spectrometry. Mean and Standard Deviation of Serum Concentrations of Tapentadol were calculated.&#xD;
Summary statistics at a given time point were only determined if at least 2 participants had observations above the lower limit of quantification (LLOQ).&#xD;
If overall only a single sample was available at one of the pre-defined time points, the measured value is presented and the standard deviation is given as N/A.</description>
          <population>The trial used sparse sampling for the assessment of Pharmacokinetic. Overall, there were 6 time points for sampling. Participants were allocated to 2 different time points for a blood sample to be taken. Some participants only had one sample taken. Some samples were below the Lower limit of quantification (LLOQ).</population>
          <units>nanogram per milliliter</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>30 minutes after administration</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="26.62" spread="NA">One sample was used at this specified time point.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>1 hour after administration</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="43.63" spread="NA">One sample was used at this specified time point.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>2 hours after administration</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="19.9" spread="7.67"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>4 hours after administration</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15.0" spread="8.92"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>6 hours after administration</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18.82" spread="NA">One sample was used at this specified time point.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>8 hours after administration</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14.6" spread="6.26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Pharmacokinetic Profile of Serum Concentrations of Tapentadol-O-glucuronide After a Single Dose of Tapentadol Oral Solution in Participants Aged 6 Months to Less Than 2 Years</title>
        <description>The pharmacokinetic profile of Tapentadol and its major metabolite tapentadol-O-glucuronide was evaluated to enable data based recommendations for the use of Tapentadol in children of different ages.&#xD;
Each participant had a single pharmacokinetic sample taken at up to 2 different pre-defined time points.&#xD;
Serum was analyzed using liquid chromatography-tandem mass spectrometry. Mean and Standard Deviation of Serum Concentrations of tapentadol-O-glucuronide were calculated.&#xD;
Summary statistics at a given time point were only determined if at least 2 participants had observations above the lower limit of quantification (LLOQ).&#xD;
If overall only a single sample was available at one of the pre-defined time points, the measured value is presented and the standard deviation is given as N/A.</description>
        <time_frame>Up to 8 hours after IMP</time_frame>
        <population>The trial used sparse sampling for the assessment of Pharmacokinetic. Overall, there were 6 time points for sampling. Participants were allocated to 2 different time points for a blood sample to be taken. Some participants only had one sample taken. Some samples were below the Lower limit of quantification (LLOQ).</population>
        <group_list>
          <group group_id="O1">
            <title>Participants Aged 6 Months to Less Than 2 Years - PK Set</title>
            <description>Infants aged 6 months to less than 2 years at the time of allocation to IMP who had quantifiable serum concentrations.</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetic Profile of Serum Concentrations of Tapentadol-O-glucuronide After a Single Dose of Tapentadol Oral Solution in Participants Aged 6 Months to Less Than 2 Years</title>
          <description>The pharmacokinetic profile of Tapentadol and its major metabolite tapentadol-O-glucuronide was evaluated to enable data based recommendations for the use of Tapentadol in children of different ages.&#xD;
Each participant had a single pharmacokinetic sample taken at up to 2 different pre-defined time points.&#xD;
Serum was analyzed using liquid chromatography-tandem mass spectrometry. Mean and Standard Deviation of Serum Concentrations of tapentadol-O-glucuronide were calculated.&#xD;
Summary statistics at a given time point were only determined if at least 2 participants had observations above the lower limit of quantification (LLOQ).&#xD;
If overall only a single sample was available at one of the pre-defined time points, the measured value is presented and the standard deviation is given as N/A.</description>
          <population>The trial used sparse sampling for the assessment of Pharmacokinetic. Overall, there were 6 time points for sampling. Participants were allocated to 2 different time points for a blood sample to be taken. Some participants only had one sample taken. Some samples were below the Lower limit of quantification (LLOQ).</population>
          <units>nanogram per milliliter</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>30 minutes after administration</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="105.7" spread="125.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>1 hour after administration</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="430.7" spread="NA">One sample was used at this specified time point.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>2 hours after administration</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="468.0" spread="248.41"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>4 hours after administration</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="348.7" spread="228.22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>6 hours after administration</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="370.2" spread="NA">One sample was used at this specified time point.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>8 hours after administration</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="285.1" spread="107.06"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Pharmacokinetic Profile of Serum Concentrations of Tapentadol-O-glucuronide After a Single Dose of Tapentadol Oral Solution in Participants Aged 1 Month to Less Than 6 Months</title>
        <description>The pharmacokinetic profile of Tapentadol and its major metabolite tapentadol-O-glucuronide was evaluated to enable data based recommendations for the use of Tapentadol in children of different ages.&#xD;
Each participant had a single pharmacokinetic sample taken at up to 2 different pre-defined time points.&#xD;
Serum was analyzed using liquid chromatography-tandem mass spectrometry. Mean and Standard Deviation of Serum Concentrations of tapentadol-O-glucuronide were calculated.&#xD;
Summary statistics at a given time point were only determined if at least 2 participants had observations above the lower limit of quantification (LLOQ).&#xD;
If overall only a single sample was available at one of the pre-defined time points, the measured value is presented and the standard deviation is given as N/A.</description>
        <time_frame>Up to 8 hours after IMP</time_frame>
        <population>The trial used sparse sampling for the assessment of Pharmacokinetic. Overall, there were 6 time points for sampling. Participants were allocated to 2 different time points for a blood sample to be taken. Some participants only had one sample taken. Some samples were below the Lower limit of quantification (LLOQ).</population>
        <group_list>
          <group group_id="O1">
            <title>Participants Aged 1 Month to Less Than 6 Months - PK Set</title>
            <description>Infants aged 1 month to less than 6 months at the time of allocation to IMP who had quantifiable serum concentrations.</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetic Profile of Serum Concentrations of Tapentadol-O-glucuronide After a Single Dose of Tapentadol Oral Solution in Participants Aged 1 Month to Less Than 6 Months</title>
          <description>The pharmacokinetic profile of Tapentadol and its major metabolite tapentadol-O-glucuronide was evaluated to enable data based recommendations for the use of Tapentadol in children of different ages.&#xD;
Each participant had a single pharmacokinetic sample taken at up to 2 different pre-defined time points.&#xD;
Serum was analyzed using liquid chromatography-tandem mass spectrometry. Mean and Standard Deviation of Serum Concentrations of tapentadol-O-glucuronide were calculated.&#xD;
Summary statistics at a given time point were only determined if at least 2 participants had observations above the lower limit of quantification (LLOQ).&#xD;
If overall only a single sample was available at one of the pre-defined time points, the measured value is presented and the standard deviation is given as N/A.</description>
          <population>The trial used sparse sampling for the assessment of Pharmacokinetic. Overall, there were 6 time points for sampling. Participants were allocated to 2 different time points for a blood sample to be taken. Some participants only had one sample taken. Some samples were below the Lower limit of quantification (LLOQ).</population>
          <units>nanogram per milliliter</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>30 minutes after administration</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="128.8" spread="NA">One sample was used at this specified time point.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>1 hour after administration</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="136.3" spread="NA">One sample was used at this specified time point.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>2 hours after administration</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="324.9" spread="116.61"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>4 hours after administration</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="449.7" spread="7.42"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>6 hours after administration</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="253.3" spread="NA">One sample was used at this specified time point.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>8 hours after administration</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="92.2" spread="63.83"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Pharmacokinetic Profile of Serum Concentrations of Tapentadol-O-glucuronide After a Single Dose of Tapentadol Oral Solution in Participants Aged From Birth to Less Than 1 Month</title>
        <description>The pharmacokinetic profile of Tapentadol and its major metabolite tapentadol-O-glucuronide was evaluated to enable data based recommendations for the use of Tapentadol in children of different ages.&#xD;
Each participant had a single pharmacokinetic sample taken at up to 2 different pre-defined time points.&#xD;
Serum was analyzed using liquid chromatography-tandem mass spectrometry. Mean and Standard Deviation of Serum Concentrations of tapentadol-O-glucuronide were calculated.&#xD;
Summary statistics at a given time point were only determined if at least 2 participants had observations above the lower limit of quantification (LLOQ).&#xD;
If overall only a single sample was available at one of the pre-defined time points, the measured value is presented and the standard deviation is given as N/A.</description>
        <time_frame>Up to 8 hours after IMP</time_frame>
        <population>The trial used sparse sampling for the assessment of Pharmacokinetic. Overall, there were 6 time points for sampling. Participants were allocated to 2 different time points for a blood sample to be taken. Some participants only had one sample taken. Some samples were below the Lower limit of quantification (LLOQ).</population>
        <group_list>
          <group group_id="O1">
            <title>Participants Aged From Birth to Less Than 1 Month - PK Set</title>
            <description>Neonates aged less than 1 month (must be ≥37 weeks gestational age) at the time of allocation to IMP who had quantifiable serum concentrations.</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetic Profile of Serum Concentrations of Tapentadol-O-glucuronide After a Single Dose of Tapentadol Oral Solution in Participants Aged From Birth to Less Than 1 Month</title>
          <description>The pharmacokinetic profile of Tapentadol and its major metabolite tapentadol-O-glucuronide was evaluated to enable data based recommendations for the use of Tapentadol in children of different ages.&#xD;
Each participant had a single pharmacokinetic sample taken at up to 2 different pre-defined time points.&#xD;
Serum was analyzed using liquid chromatography-tandem mass spectrometry. Mean and Standard Deviation of Serum Concentrations of tapentadol-O-glucuronide were calculated.&#xD;
Summary statistics at a given time point were only determined if at least 2 participants had observations above the lower limit of quantification (LLOQ).&#xD;
If overall only a single sample was available at one of the pre-defined time points, the measured value is presented and the standard deviation is given as N/A.</description>
          <population>The trial used sparse sampling for the assessment of Pharmacokinetic. Overall, there were 6 time points for sampling. Participants were allocated to 2 different time points for a blood sample to be taken. Some participants only had one sample taken. Some samples were below the Lower limit of quantification (LLOQ).</population>
          <units>nanogram per milliliter</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>30 minutes after administration</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="74.38" spread="NA">One sample was used at this specified time point.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>1 hour after administration</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="209" spread="NA">One sample was used at this specified time point.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>2 hours after administration</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="98.5" spread="2.62"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>4 hours after administration</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="147.6" spread="53.74"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>6 hours after administration</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="224.8" spread="NA">One sample was used at this specified time point.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>8 hours after administration</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="174.1" spread="11.03"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Change From Baseline (Visit 1, After Surgery) in Pain Intensity</title>
        <description>The change from baseline in pain intensity using the Face, Legs, Activity, Cry, Consolability Scale (FLACC Scale) at 15 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, 8 hours, 12 hours, and 15 hours after a single dose of tapentadol.&#xD;
The FLACC Scale is a behavioral scale for scoring postoperative pain in young children. It includes five categories of pain behaviors, including facial expression, leg movement, activity, cry, and consolability. The scale is scored in a range of 0-10 with 0 representing no pain.&#xD;
The pain intensity scores were summarized descriptively per scheduled time point.</description>
        <time_frame>Baseline; up to 15 hours after study medication</time_frame>
        <population>For the Arm/Group &quot;Participants aged 6 months to less than 2 years&quot; only 7 values were available at the timepoint &quot;6 hours after administration&quot;.</population>
        <group_list>
          <group group_id="O1">
            <title>Participants Aged 6 Months to Less Than 2 Years.</title>
            <description>Infants aged 6 months to less than 2 years at the time of allocation to IMP. Participants received a single dose of tapentadol oral solution postoperatively. The dose administered depended on the age of the subject and the body weight.&#xD;
Infants aged 6 months to less than 2 years received a dose of 0.75 mg/kg.</description>
          </group>
          <group group_id="O2">
            <title>Participants Aged 1 Month to Less Than 6 Months.</title>
            <description>Infants aged 1 month to less than 6 months at the time of allocation to IMP. Participants received a single dose of tapentadol oral solution postoperatively. The dose administered depended on the age of the subject and the body weight.&#xD;
Infants aged 1 month to less than 6 months received a dose of 0.60 mg/kg.</description>
          </group>
          <group group_id="O3">
            <title>Participants Aged From Birth to Less Than 1 Month.</title>
            <description>Neonates aged less than 1 month at the time of allocation to IMP (must be ≥37 weeks gestational age).&#xD;
Participants received a single dose of tapentadol oral solution postoperatively. The dose administered depended on the age of the subject and the body weight.&#xD;
Neonates aged less than 1 month received a dose of 0.50 mg/kg.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline (Visit 1, After Surgery) in Pain Intensity</title>
          <description>The change from baseline in pain intensity using the Face, Legs, Activity, Cry, Consolability Scale (FLACC Scale) at 15 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, 8 hours, 12 hours, and 15 hours after a single dose of tapentadol.&#xD;
The FLACC Scale is a behavioral scale for scoring postoperative pain in young children. It includes five categories of pain behaviors, including facial expression, leg movement, activity, cry, and consolability. The scale is scored in a range of 0-10 with 0 representing no pain.&#xD;
The pain intensity scores were summarized descriptively per scheduled time point.</description>
          <population>For the Arm/Group &quot;Participants aged 6 months to less than 2 years&quot; only 7 values were available at the timepoint &quot;6 hours after administration&quot;.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>15 minutes after administration</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                    <count group_id="O2" value="6"/>
                    <count group_id="O3" value="5"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.8" spread="3.1"/>
                    <measurement group_id="O2" value="-1.3" spread="2.8"/>
                    <measurement group_id="O3" value="-1.6" spread="1.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>30 minutes after administration</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                    <count group_id="O2" value="6"/>
                    <count group_id="O3" value="5"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.1" spread="2.6"/>
                    <measurement group_id="O2" value="-3.0" spread="3.6"/>
                    <measurement group_id="O3" value="-1.4" spread="1.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>1 hour after administration</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                    <count group_id="O2" value="6"/>
                    <count group_id="O3" value="5"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.0" spread="3.6"/>
                    <measurement group_id="O2" value="-2.7" spread="4.5"/>
                    <measurement group_id="O3" value="0.0" spread="3.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>2 hours after administration</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                    <count group_id="O2" value="6"/>
                    <count group_id="O3" value="5"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.8" spread="2.9"/>
                    <measurement group_id="O2" value="-3.0" spread="3.9"/>
                    <measurement group_id="O3" value="-0.4" spread="2.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>4 hours after administration</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                    <count group_id="O2" value="6"/>
                    <count group_id="O3" value="5"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.6" spread="3.4"/>
                    <measurement group_id="O2" value="-2.2" spread="3.3"/>
                    <measurement group_id="O3" value="-0.4" spread="2.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>6 hours after administration</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                    <count group_id="O2" value="6"/>
                    <count group_id="O3" value="5"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.9" spread="3.1"/>
                    <measurement group_id="O2" value="-1.7" spread="4.8"/>
                    <measurement group_id="O3" value="-0.4" spread="2.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>8 hours after administration</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                    <count group_id="O2" value="6"/>
                    <count group_id="O3" value="5"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.5" spread="2.5"/>
                    <measurement group_id="O2" value="-3.0" spread="3.2"/>
                    <measurement group_id="O3" value="-1.2" spread="1.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>12 hours after administration</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                    <count group_id="O2" value="6"/>
                    <count group_id="O3" value="5"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.4" spread="2.8"/>
                    <measurement group_id="O2" value="-3.5" spread="3.8"/>
                    <measurement group_id="O3" value="-1.4" spread="1.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>15 hours after administration</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                    <count group_id="O2" value="6"/>
                    <count group_id="O3" value="5"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.1" spread="3.5"/>
                    <measurement group_id="O2" value="-3.8" spread="3.9"/>
                    <measurement group_id="O3" value="-1.0" spread="2.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Any Adverse Events (AE) that started on the intake of the IMP (investigational medicinal product) up to the end of the therapeutic reach of the IMP. Any pre-treatment AE which worsened (change in intensity, frequency or quality) after IMP administration compared to the complaint present before IMP intake have been recorded as a new AE.</time_frame>
      <desc>The therapeutic reach is the time after IMP intake that a subject is still considered to be potentially affected by a study drug. For tapentadol oral solution, the therapeutic reach is defined as 48 hours after (last) IMP intake.</desc>
      <group_list>
        <group group_id="E1">
          <title>Participants Aged 6 Months to Less Than 2 Years.</title>
          <description>Infants aged 6 months to less than 2 years at the time of allocation to IMP. Participants received a single dose of tapentadol oral solution postoperatively. The dose administered depended on the age of the subject and the body weight.&#xD;
Infants aged 6 months to less than 2 years received a dose of 0.75 mg/kg.</description>
        </group>
        <group group_id="E2">
          <title>Participants Aged 1 Month to Less Than 6 Months.</title>
          <description>Infants aged 1 month to less than 6 months at the time of allocation to IMP. Participants received a single dose of tapentadol oral solution postoperatively. The dose administered depended on the age of the subject and the body weight.&#xD;
Infants aged 1 month to less than 6 months received a dose of 0.60 mg/kg.</description>
        </group>
        <group group_id="E3">
          <title>Participants Aged From Birth to Less Than 1 Month.</title>
          <description>Neonates aged less than 1 month at the time of allocation to IMP (must be ≥37 weeks gestational age).&#xD;
Participants received a single dose of tapentadol oral solution postoperatively. The dose administered depended on the age of the subject and the body weight.&#xD;
Neonates aged less than 1 month received a dose of 0.50 mg/kg.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA (19.1)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Junctional ectopic tachycardia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal distension</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="2" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Stoma site erythema</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Wound dehiscence</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Blood creatine phosphokinase increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Blood potassium decreased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Oxygen saturation decreased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="3" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Renal failure</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Tachypnoea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>The sponsor reserves the right to review any publication pertaining to the trial before it is submitted for publication. Neither party has the right to prohibit publication unless publication can be shown to affect possible patent rights.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Director of Clinical Trials</name_or_title>
      <organization>Grünenthal GmbH</organization>
      <phone>+49 241 569 ext 3223</phone>
      <email>Clinical-Trials@grunenthal.com</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02221674
org study id: KF5503-72
secondary id: 2014-000623-24
secondary id: U1111-1153-1662
secondary id: R331333PAI2007
nct id: NCT02221674
lead sponsor: 
collaborator: 
has dmc: Yes
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.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Pharmacokinetic Evaluation Based on Serum Concentrations of Tapentadol After a Single Dose of Tapentadol Oral Solution in Participants Aged 6 Months to Less Than 2 Years
time frame: Up to 8 hours after IMP administration
description: The pharmacokinetic profile of Tapentadol and its major metabolite tapentadol-O-glucuronide was evaluated to enable data based recommendations for the use of Tapentadol in children of different ages.
Each participant had a single pharmacokinetic sample taken at up to 2 different pre-defined time points.
Serum was analyzed using liquid chromatography-tandem mass spectrometry. Mean and Standard Deviation of Serum Concentrations of Tapentadol were calculated.
Summary statistics at a given time point were only determined if at least 2 participants had observations above the lower limit of quantification (LLOQ).
If overall only a single sample was available at one of the pre-defined time points, the measured value is presented and the standard deviation is given as N/A.
measure: Pharmacokinetic Evaluation Based on Serum Concentrations of Tapentadol After a Single Dose of Tapentadol Oral Solution in Participants Aged 1 Month to Less Than 6 Months
time frame: Up to 8 hours after IMP administration
description: The pharmacokinetic profile of Tapentadol and its major metabolite tapentadol-O-glucuronide was evaluated to enable data based recommendations for the use of Tapentadol in children of different ages.
Each participant had a single pharmacokinetic sample taken at up to 2 different pre-defined time points.
Serum was analyzed using liquid chromatography-tandem mass spectrometry. Mean and Standard Deviation of Serum Concentrations of Tapentadol were calculated.
Summary statistics at a given time point were only determined if at least 2 participants had observations above the lower limit of quantification (LLOQ).
If overall only a single sample was available at one of the pre-defined time points, the measured value is presented and the standard deviation is given as N/A.
measure: Pharmacokinetic Evaluation Based on Serum Concentrations of Tapentadol After a Single Dose of Tapentadol Oral Solution in Participants Aged From Birth to Less Than 1 Month
time frame: Up to 8 hours after IMP
description: The pharmacokinetic profile of Tapentadol and its major metabolite tapentadol-O-glucuronide was evaluated to enable data based recommendations for the use of Tapentadol in children of different ages.
Each participant had a single pharmacokinetic sample taken at up to 2 different pre-defined time points.
Serum was analyzed using liquid chromatography-tandem mass spectrometry. Mean and Standard Deviation of Serum Concentrations of Tapentadol were calculated.
Summary statistics at a given time point were only determined if at least 2 participants had observations above the lower limit of quantification (LLOQ).
If overall only a single sample was available at one of the pre-defined time points, the measured value is presented and the standard deviation is given as N/A.
measure: Pharmacokinetic Profile of Serum Concentrations of Tapentadol-O-glucuronide After a Single Dose of Tapentadol Oral Solution in Participants Aged 6 Months to Less Than 2 Years
time frame: Up to 8 hours after IMP
description: The pharmacokinetic profile of Tapentadol and its major metabolite tapentadol-O-glucuronide was evaluated to enable data based recommendations for the use of Tapentadol in children of different ages.
Each participant had a single pharmacokinetic sample taken at up to 2 different pre-defined time points.
Serum was analyzed using liquid chromatography-tandem mass spectrometry. Mean and Standard Deviation of Serum Concentrations of tapentadol-O-glucuronide were calculated.
Summary statistics at a given time point were only determined if at least 2 participants had observations above the lower limit of quantification (LLOQ).
If overall only a single sample was available at one of the pre-defined time points, the measured value is presented and the standard deviation is given as N/A.
measure: Pharmacokinetic Profile of Serum Concentrations of Tapentadol-O-glucuronide After a Single Dose of Tapentadol Oral Solution in Participants Aged 1 Month to Less Than 6 Months
time frame: Up to 8 hours after IMP
description: The pharmacokinetic profile of Tapentadol and its major metabolite tapentadol-O-glucuronide was evaluated to enable data based recommendations for the use of Tapentadol in children of different ages.
Each participant had a single pharmacokinetic sample taken at up to 2 different pre-defined time points.
Serum was analyzed using liquid chromatography-tandem mass spectrometry. Mean and Standard Deviation of Serum Concentrations of tapentadol-O-glucuronide were calculated.
Summary statistics at a given time point were only determined if at least 2 participants had observations above the lower limit of quantification (LLOQ).
If overall only a single sample was available at one of the pre-defined time points, the measured value is presented and the standard deviation is given as N/A.
measure: Pharmacokinetic Profile of Serum Concentrations of Tapentadol-O-glucuronide After a Single Dose of Tapentadol Oral Solution in Participants Aged From Birth to Less Than 1 Month
time frame: Up to 8 hours after IMP
description: The pharmacokinetic profile of Tapentadol and its major metabolite tapentadol-O-glucuronide was evaluated to enable data based recommendations for the use of Tapentadol in children of different ages.
Each participant had a single pharmacokinetic sample taken at up to 2 different pre-defined time points.
Serum was analyzed using liquid chromatography-tandem mass spectrometry. Mean and Standard Deviation of Serum Concentrations of tapentadol-O-glucuronide were calculated.
Summary statistics at a given time point were only determined if at least 2 participants had observations above the lower limit of quantification (LLOQ).
If overall only a single sample was available at one of the pre-defined time points, the measured value is presented and the standard deviation is given as N/A.
measure: Change From Baseline (Visit 1, After Surgery) in Pain Intensity
time frame: Baseline; up to 15 hours after study medication
description: The change from baseline in pain intensity using the Face, Legs, Activity, Cry, Consolability Scale (FLACC Scale) at 15 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, 8 hours, 12 hours, and 15 hours after a single dose of tapentadol.
The FLACC Scale is a behavioral scale for scoring postoperative pain in young children. It includes five categories of pain behaviors, including facial expression, leg movement, activity, cry, and consolability. The scale is scored in a range of 0-10 with 0 representing no pain.
The pain intensity scores were summarized descriptively per scheduled time point.
arm group label: Tapentadol
arm group type: Experimental
description: Tapentadol 4 mg/mL immediate release oral solution, single dose post-operatively.
intervention type: Drug
intervention name: Tapentadol
arm group label: Tapentadol
other name: Palexia®
other name: Nucynta®
other name: Yantil®
criteria: 
gender: All
minimum age: 1 Day
maximum age: 23 Months
healthy volunteers: No
last name: Clinical Trial Director
role: Study Director
affiliation: Grünenthal GmbH
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Poland
country: United Kingdom
country: United States
responsible party type: Sponsor
mesh term: Pain, Postoperative
mesh term: Tapentadol
sharing ipd: Yes
ipd description: 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.
ipd url: http://www.grunenthal.com/grt-web/Grunenthal_Group/Research_Development/Grunenthal_Clinical_Trials/Data_Sharing/296200025.jsp
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 