Moderate to Severe Acute Postoperative Pain
Conditions
Keywords
Post-surgical pain, Opioid
Brief summary
This is a multicenter, open-label (all people involved know the identity of the intervention), single dose trial to evaluate the pharmacokinetic (PK) profile (how drugs are absorbed in the body, how are they distributed within the body and how are they removed from the body over time) in children aged from birth to less than 2 years after a surgical procedure that routinely produces moderate to severe acute post-surgical pain. The trial will also evaluate the safety and tolerability of tapentadol oral solution in the population studied and the effect of tapentadol oral solution on pain.
Detailed description
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.
Interventions
DRUGTapentadol
Sponsors
Depomed
Grünenthal GmbH
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Days to 23 Months
Healthy volunteers
No
Inclusion criteria
* The participant's parent(s) or legal guardian(s) have given written informed consent to participate. * Participant is not obese (e.g., a body weight above the 97th percentile for children based on the World Health Organization weight charts) with a minimum body weight of 2.5 kg. * Physical status rated not higher than P3 on the American Society of Anesthesiologists physical status classification in participants aged from 1 month to less than 2 years. * Participant has undergone surgery that, in the investigator's opinion, would reliably produce moderate to severe pain requiring opioid treatment. * At the time of allocation to IMP, participant has a sedation score that is not higher than 2 (moderately sedated) on the University of Michigan Sedation Scale with the exception of participants who are mechanically ventilated in age subgroup 3, has a functioning gastrointestinal tract after surgery, and can tolerate medication administered orally or via a feeding tube at the time of allocation to IMP. * Participant has a reliable venous vascular access for pharmacokinetic blood sampling.
Exclusion criteria
* The participant's parent(s) or legal guardian(s) is an employee of the investigator or trial site, with direct involvement in this trial or other trials under the direction of that investigator or trial site, or the participant, or participant's parent(s), or legal guardian(s) is a family member of the employees or the investigator. * Participant has been previously exposed to tapentadol. * Participant has received an experimental drug or used an experimental medical device within 28 days before allocation to study medication, or within a period less than 10 times the drug's half-life, whichever is longer. * Concomitant participation in another interventional clinical trial for the duration of this trial. * Participant has undergone brain surgery. * Participant has undergone a surgery that is expected to affect the absorption of tapentadol (e.g., to the gastrointestinal tract). * Participant has a history or current condition of any one of the following: * Seizure disorder. * Traumatic or hypoxic brain injury, i.e. brain contusion, stroke, transient ischemic attack, intracranial bleeding or hematoma, brain neoplasm. * Participant has a history or current condition of any one of the following: * Moderate to severe renal impairment. * Moderate to severe hepatic impairment, congestive hepatopathy, or hepatic portosystemic shunting. * Clinically relevant abnormal pulmonary function or clinically relevant respiratory disease that in the opinion of the investigator would put the participant at risk for developing respiratory depression, unless the participant is mechanically ventilated in age subgroup 3. * Participant has signs or symptoms of congestive heart failure (e.g., requiring more than minimal inotropic support, an abnormal lactic acid value greater than 2-times upper limit of normal), or hemorrhagic disorder following surgery. * Minimal inotropic medication is defined as: * Dopamine less or equal to 5 microgram/kg per minute. * Epinephrine less or equal to 0.03 microgram/kg per minute (but not both dopamine and epinephrine). * Milrinone less or equal to 0.5 microgram/kg per minute or less. * Participant has a concomitant disease or disorder (e.g., endocrine, metabolic, neurological, or psychiatric disorder, or a febrile seizure or paralytic ileus) that in the opinion of the investigator may affect or compromise participant's safety during the trial participation. * Participant has cognitive or developmental impairment such that trial participation may affect or compromise the participant's safety, or the participant's ability to comply with the protocol requirements (as appropriate for the participant's age), in the investigator's judgment. Otherwise, participant's with cognitive or developmental impairment may be enrolled in the trial. * Participant has a clinically relevant history of hypersensitivity, allergy, or contraindication to tapentadol (or ingredients). * Participant has: * Clinically relevant abnormal 12-lead ECG in the investigator's judgment. * Signs of pre-excitation syndrome. * Corrected QT (QTcF) interval greater than 460 ms. Participant may be allocated to Investigational Medicinal Product with values greater than 460 ms if, in the investigator's opinion, the value is a consequence of cardiac surgery and is not considered clinically significant. * Participant has clinically relevant abnormal lab values from a sample obtained postoperatively and prior to allocation to study medication. The following specifications will apply: * Aspartate transaminase or alanine transaminase is greater than 2.5-times upper limit of normal. * Total bilirubin is greater than 2-times upper limit of normal and direct bilirubin is greater than 20% of the total bilirubin, and for participants in age subgroup 3, the presence of pathological jaundice in the opinion of the investigator. * Glomerular filtration rate (calculated according to Schwartz et al. 1984): * less than 20 mL/min/1.73 m2 for participants less than 1 week old. * less than 30 mL/min/1.73 m2 for participants 1 week to 8 weeks old. * less than 50 mL/min/1.73 m2 for participants more than 8 weeks old. * Other parameters (in the investigator's judgment). * Signs or symptoms indicative of a systemic infection within 24 hours prior to allocation to study medication. * Participant has been administered a prohibited medication. * The mother of a newborn or the breastfeeding mother of a participant was administered a prohibited medication. * At the time of dosing, in the investigator's judgment, the participant has either of the following: * Clinically unstable upper or lower airway conditions or respiratory depression (unless the participant is mechanically ventilated in age subgroup 3). * Clinically unstable systolic or diastolic blood pressure, heart rate, or respiratory rate. * Participant has a peripheral oxygen saturation (SpO2) \<92% for acyanotic participant, or \<75% for cyanotic participant, with or without supplemental oxygen via nasal cannula or high flow nasal cannula, at the time of allocation to Investigational Medicinal Product. * For age subgroup 1 and age subgroup 2, participant requires continuous positive airway pressure or mechanical ventilation, at the time of allocation to Investigational Medicinal Product.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Up to 8 hours after IMP | 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. |
| 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 | Up to 8 hours after IMP administration | 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. |
| 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 | Up to 8 hours after IMP administration | 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. |
| 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 | Up to 8 hours after IMP | 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. |
| 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 | Up to 8 hours after IMP | 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. |
| 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 | Up to 8 hours after IMP | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline (Visit 1, After Surgery) in Pain Intensity | Baseline; up to 15 hours after study medication | 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. |
Countries
Poland, United Kingdom, United States
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.
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. 21 patients were enrolled but not allocated.
Participants by arm
| Arm | Count |
|---|---|
| Participants Aged 6 Months to Less Than 2 Years 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.
Infants aged 6 months to less than 2 years received a dose of 0.75 mg/kg. | 8 |
| Participants Aged 1 Month to Less Than 6 Months 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.
Infants aged 1 month to less than 6 months received a dose of 0.60 mg/kg. | 6 |
| Participants Aged From Birth to Less Than 1 Month Neonates aged less than 1 month at the time of allocation to IMP (must be ≥37 weeks gestational age).
Participants received a single dose of tapentadol oral solution postoperatively. The dose administered depended on the age of the subject and the body weight.
Neonates aged less than 1 month received a dose of 0.50 mg/kg. | 5 |
| Total | 19 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Participants Aged 6 Months to Less Than 2 Years | Participants Aged 1 Month to Less Than 6 Months | Participants Aged From Birth to Less Than 1 Month | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 8 Participants | 6 Participants | 5 Participants | 19 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 420.0 days STANDARD_DEVIATION 147.8 | 92.8 days STANDARD_DEVIATION 37.9 | 14.6 days STANDARD_DEVIATION 8.5 | 210.0 days STANDARD_DEVIATION 209 |
| Baseline Pain Intensity using the FLACC Scale | 2.8 units on a scale STANDARD_DEVIATION 2.9 | 3.8 units on a scale STANDARD_DEVIATION 3.9 | 1.6 units on a scale STANDARD_DEVIATION 1.5 | 2.8 units on a scale STANDARD_DEVIATION 3 |
| Body Mass Index (BMI) | 17.11 kilogram per square meter STANDARD_DEVIATION 1.36 | 15.28 kilogram per square meter STANDARD_DEVIATION 1.31 | 13.36 kilogram per square meter STANDARD_DEVIATION 2.49 | 15.55 kilogram per square meter STANDARD_DEVIATION 2.24 |
| Height | 73.3 centimeter STANDARD_DEVIATION 5.2 | 62.0 centimeter STANDARD_DEVIATION 4.3 | 53.4 centimeter STANDARD_DEVIATION 4.4 | 64.5 centimeter STANDARD_DEVIATION 9.5 |
| Region of Enrollment Poland | 0 participants | 0 participants | 3 participants | 3 participants |
| Region of Enrollment United Kingdom | 1 participants | 0 participants | 0 participants | 1 participants |
| Region of Enrollment United States | 7 participants | 6 participants | 2 participants | 15 participants |
| Sex: Female, Male Female | 4 Participants | 2 Participants | 3 Participants | 9 Participants |
| Sex: Female, Male Male | 4 Participants | 4 Participants | 2 Participants | 10 Participants |
| Weight | 9.21 kilogram STANDARD_DEVIATION 1.5 | 5.92 kilogram STANDARD_DEVIATION 1.18 | 3.78 kilogram STANDARD_DEVIATION 0.66 | 6.74 kilogram STANDARD_DEVIATION 2.59 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 6 | 0 / 5 |
| other Total, other adverse events | 3 / 8 | 3 / 6 | 2 / 5 |
| serious Total, serious adverse events | 0 / 8 | 0 / 6 | 0 / 5 |
Outcome results
Primary
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
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.
Time frame: Up to 8 hours after IMP administration
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).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Participants Aged 6 Months to Less Than 2 Years - PK Set | 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 | 30 minutes after administration | 8.3 nanogram per milliliter | Standard Deviation 6.3 |
| Participants Aged 6 Months to Less Than 2 Years - PK Set | 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 | 1 hour after administration | 35.27 nanogram per milliliter | — |
| Participants Aged 6 Months to Less Than 2 Years - PK Set | 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 | 2 hours after administration | 27.3 nanogram per milliliter | Standard Deviation 0.81 |
| Participants Aged 6 Months to Less Than 2 Years - PK Set | 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 | 4 hours after administration | 25.9 nanogram per milliliter | Standard Deviation 10.33 |
| Participants Aged 6 Months to Less Than 2 Years - PK Set | 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 | 6 hours after administration | 32.75 nanogram per milliliter | — |
| Participants Aged 6 Months to Less Than 2 Years - PK Set | 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 | 8 hours after administration | 5.6 nanogram per milliliter | Standard Deviation 1.81 |
Primary
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
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.
Time frame: Up to 8 hours after IMP administration
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).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Participants Aged 6 Months to Less Than 2 Years - PK Set | 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 | 30 minutes after administration | 9.8 nanogram per milliliter | Standard Deviation 5.21 |
| Participants Aged 6 Months to Less Than 2 Years - PK Set | 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 | 1 hour after administration | 18.79 nanogram per milliliter | — |
| Participants Aged 6 Months to Less Than 2 Years - PK Set | 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 | 2 hours after administration | 32.2 nanogram per milliliter | Standard Deviation 14.92 |
| Participants Aged 6 Months to Less Than 2 Years - PK Set | 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 | 4 hours after administration | 11.1 nanogram per milliliter | Standard Deviation 5.97 |
| Participants Aged 6 Months to Less Than 2 Years - PK Set | 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 | 6 hours after administration | 14.85 nanogram per milliliter | — |
| Participants Aged 6 Months to Less Than 2 Years - PK Set | 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 | 8 hours after administration | 10.7 nanogram per milliliter | Standard Deviation 4.15 |
Primary
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
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.
Time frame: Up to 8 hours after IMP
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).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Participants Aged 6 Months to Less Than 2 Years - PK Set | 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 | 30 minutes after administration | 26.62 nanogram per milliliter | — |
| Participants Aged 6 Months to Less Than 2 Years - PK Set | 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 | 1 hour after administration | 43.63 nanogram per milliliter | — |
| Participants Aged 6 Months to Less Than 2 Years - PK Set | 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 | 2 hours after administration | 19.9 nanogram per milliliter | Standard Deviation 7.67 |
| Participants Aged 6 Months to Less Than 2 Years - PK Set | 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 | 4 hours after administration | 15.0 nanogram per milliliter | Standard Deviation 8.92 |
| Participants Aged 6 Months to Less Than 2 Years - PK Set | 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 | 6 hours after administration | 18.82 nanogram per milliliter | — |
| Participants Aged 6 Months to Less Than 2 Years - PK Set | 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 | 8 hours after administration | 14.6 nanogram per milliliter | Standard Deviation 6.26 |
Primary
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
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.
Time frame: Up to 8 hours after IMP
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).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Participants Aged 6 Months to Less Than 2 Years - PK Set | 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 | 30 minutes after administration | 128.8 nanogram per milliliter | — |
| Participants Aged 6 Months to Less Than 2 Years - PK Set | 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 | 1 hour after administration | 136.3 nanogram per milliliter | — |
| Participants Aged 6 Months to Less Than 2 Years - PK Set | 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 | 2 hours after administration | 324.9 nanogram per milliliter | Standard Deviation 116.61 |
| Participants Aged 6 Months to Less Than 2 Years - PK Set | 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 | 4 hours after administration | 449.7 nanogram per milliliter | Standard Deviation 7.42 |
| Participants Aged 6 Months to Less Than 2 Years - PK Set | 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 | 6 hours after administration | 253.3 nanogram per milliliter | — |
| Participants Aged 6 Months to Less Than 2 Years - PK Set | 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 | 8 hours after administration | 92.2 nanogram per milliliter | Standard Deviation 63.83 |
Primary
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
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.
Time frame: Up to 8 hours after IMP
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).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Participants Aged 6 Months to Less Than 2 Years - PK Set | 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 | 30 minutes after administration | 105.7 nanogram per milliliter | Standard Deviation 125 |
| Participants Aged 6 Months to Less Than 2 Years - PK Set | 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 | 1 hour after administration | 430.7 nanogram per milliliter | — |
| Participants Aged 6 Months to Less Than 2 Years - PK Set | 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 | 2 hours after administration | 468.0 nanogram per milliliter | Standard Deviation 248.41 |
| Participants Aged 6 Months to Less Than 2 Years - PK Set | 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 | 4 hours after administration | 348.7 nanogram per milliliter | Standard Deviation 228.22 |
| Participants Aged 6 Months to Less Than 2 Years - PK Set | 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 | 6 hours after administration | 370.2 nanogram per milliliter | — |
| Participants Aged 6 Months to Less Than 2 Years - PK Set | 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 | 8 hours after administration | 285.1 nanogram per milliliter | Standard Deviation 107.06 |
Primary
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
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.
Time frame: Up to 8 hours after IMP
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).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Participants Aged 6 Months to Less Than 2 Years - PK Set | 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 | 4 hours after administration | 147.6 nanogram per milliliter | Standard Deviation 53.74 |
| Participants Aged 6 Months to Less Than 2 Years - PK Set | 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 | 6 hours after administration | 224.8 nanogram per milliliter | — |
| Participants Aged 6 Months to Less Than 2 Years - PK Set | 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 | 8 hours after administration | 174.1 nanogram per milliliter | Standard Deviation 11.03 |
| Participants Aged 6 Months to Less Than 2 Years - PK Set | 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 | 30 minutes after administration | 74.38 nanogram per milliliter | — |
| Participants Aged 6 Months to Less Than 2 Years - PK Set | 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 | 1 hour after administration | 209 nanogram per milliliter | — |
| Participants Aged 6 Months to Less Than 2 Years - PK Set | 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 | 2 hours after administration | 98.5 nanogram per milliliter | Standard Deviation 2.62 |
Other Pre-specified
Change From Baseline (Visit 1, After Surgery) in Pain Intensity
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.
Time frame: Baseline; up to 15 hours after study medication
Population: For the Arm/Group Participants aged 6 months to less than 2 years only 7 values were available at the timepoint 6 hours after administration.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Participants Aged 6 Months to Less Than 2 Years - PK Set | Change From Baseline (Visit 1, After Surgery) in Pain Intensity | 2 hours after administration | -2.8 units on a scale | Standard Deviation 2.9 |
| Participants Aged 6 Months to Less Than 2 Years - PK Set | Change From Baseline (Visit 1, After Surgery) in Pain Intensity | 15 hours after administration | -2.1 units on a scale | Standard Deviation 3.5 |
| Participants Aged 6 Months to Less Than 2 Years - PK Set | Change From Baseline (Visit 1, After Surgery) in Pain Intensity | 6 hours after administration | -1.9 units on a scale | Standard Deviation 3.1 |
| Participants Aged 6 Months to Less Than 2 Years - PK Set | Change From Baseline (Visit 1, After Surgery) in Pain Intensity | 4 hours after administration | -1.6 units on a scale | Standard Deviation 3.4 |
| Participants Aged 6 Months to Less Than 2 Years - PK Set | Change From Baseline (Visit 1, After Surgery) in Pain Intensity | 15 minutes after administration | -0.8 units on a scale | Standard Deviation 3.1 |
| Participants Aged 6 Months to Less Than 2 Years - PK Set | Change From Baseline (Visit 1, After Surgery) in Pain Intensity | 12 hours after administration | -2.4 units on a scale | Standard Deviation 2.8 |
| Participants Aged 6 Months to Less Than 2 Years - PK Set | Change From Baseline (Visit 1, After Surgery) in Pain Intensity | 1 hour after administration | -2.0 units on a scale | Standard Deviation 3.6 |
| Participants Aged 6 Months to Less Than 2 Years - PK Set | Change From Baseline (Visit 1, After Surgery) in Pain Intensity | 30 minutes after administration | -1.1 units on a scale | Standard Deviation 2.6 |
| Participants Aged 6 Months to Less Than 2 Years - PK Set | Change From Baseline (Visit 1, After Surgery) in Pain Intensity | 8 hours after administration | -2.5 units on a scale | Standard Deviation 2.5 |
| Participants Aged 1 Month to Less Than 6 Months. | Change From Baseline (Visit 1, After Surgery) in Pain Intensity | 4 hours after administration | -2.2 units on a scale | Standard Deviation 3.3 |
| Participants Aged 1 Month to Less Than 6 Months. | Change From Baseline (Visit 1, After Surgery) in Pain Intensity | 15 minutes after administration | -1.3 units on a scale | Standard Deviation 2.8 |
| Participants Aged 1 Month to Less Than 6 Months. | Change From Baseline (Visit 1, After Surgery) in Pain Intensity | 30 minutes after administration | -3.0 units on a scale | Standard Deviation 3.6 |
| Participants Aged 1 Month to Less Than 6 Months. | Change From Baseline (Visit 1, After Surgery) in Pain Intensity | 1 hour after administration | -2.7 units on a scale | Standard Deviation 4.5 |
| Participants Aged 1 Month to Less Than 6 Months. | Change From Baseline (Visit 1, After Surgery) in Pain Intensity | 2 hours after administration | -3.0 units on a scale | Standard Deviation 3.9 |
| Participants Aged 1 Month to Less Than 6 Months. | Change From Baseline (Visit 1, After Surgery) in Pain Intensity | 6 hours after administration | -1.7 units on a scale | Standard Deviation 4.8 |
| Participants Aged 1 Month to Less Than 6 Months. | Change From Baseline (Visit 1, After Surgery) in Pain Intensity | 8 hours after administration | -3.0 units on a scale | Standard Deviation 3.2 |
| Participants Aged 1 Month to Less Than 6 Months. | Change From Baseline (Visit 1, After Surgery) in Pain Intensity | 12 hours after administration | -3.5 units on a scale | Standard Deviation 3.8 |
| Participants Aged 1 Month to Less Than 6 Months. | Change From Baseline (Visit 1, After Surgery) in Pain Intensity | 15 hours after administration | -3.8 units on a scale | Standard Deviation 3.9 |
| Participants Aged From Birth to Less Than 1 Month. | Change From Baseline (Visit 1, After Surgery) in Pain Intensity | 1 hour after administration | 0.0 units on a scale | Standard Deviation 3.7 |
| Participants Aged From Birth to Less Than 1 Month. | Change From Baseline (Visit 1, After Surgery) in Pain Intensity | 15 minutes after administration | -1.6 units on a scale | Standard Deviation 1.5 |
| Participants Aged From Birth to Less Than 1 Month. | Change From Baseline (Visit 1, After Surgery) in Pain Intensity | 8 hours after administration | -1.2 units on a scale | Standard Deviation 1.1 |
| Participants Aged From Birth to Less Than 1 Month. | Change From Baseline (Visit 1, After Surgery) in Pain Intensity | 30 minutes after administration | -1.4 units on a scale | Standard Deviation 1.5 |
| Participants Aged From Birth to Less Than 1 Month. | Change From Baseline (Visit 1, After Surgery) in Pain Intensity | 15 hours after administration | -1.0 units on a scale | Standard Deviation 2.1 |
| Participants Aged From Birth to Less Than 1 Month. | Change From Baseline (Visit 1, After Surgery) in Pain Intensity | 4 hours after administration | -0.4 units on a scale | Standard Deviation 2.3 |
| Participants Aged From Birth to Less Than 1 Month. | Change From Baseline (Visit 1, After Surgery) in Pain Intensity | 2 hours after administration | -0.4 units on a scale | Standard Deviation 2.6 |
| Participants Aged From Birth to Less Than 1 Month. | Change From Baseline (Visit 1, After Surgery) in Pain Intensity | 12 hours after administration | -1.4 units on a scale | Standard Deviation 1.5 |
| Participants Aged From Birth to Less Than 1 Month. | Change From Baseline (Visit 1, After Surgery) in Pain Intensity | 6 hours after administration | -0.4 units on a scale | Standard Deviation 2.3 |