E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Postoperative Pain in Children and Adolescents |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10036236 |
E.1.2 | Term | Postoperative pain relief |
E.1.2 | System Organ Class | 100000004865 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10054711 |
E.1.2 | Term | Postoperative pain |
E.1.2 | System Organ Class | 100000004863 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the pharmacokinetic profile of tapentadol and its major metabolite tapentadol-O-glucuronide after the administration of a single dose of tapentadol oral solution in children and adolescents aged from 2 years to less than 18 years after a surgical procedure that routinely produces acute severe post-surgical pain. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the safety of tapentadol oral solution in the population studied.
To explore the effect of tapentadol oral solution on pain intensity in the population studied. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• A maximum body weight of 85.0 kg.
• A minimum body weight of 10 kg for participants aged 2 years to less than 3 years old.
• If female and post-menarchal, or 12 years or older, the subject has a negative urine pregnancy test within 24 hours before surgery.
• Having completed either dental surgery or tonsillectomy with or without adenoidectomy surgery (age group: 6 to less than 18 years of age).
• Having completed ear, nose, or throat surgery (including but not limited to tonsillectomy (age group: 2 to less than 3 years of age).
• Participant aged 6 to less than 18 years has a post-operative pain intensity score greater than or equal to 4 on the Color Analog Scale (CAS) as a result of the surgical procedure or the participant has a pain level that the usual standard of care following the surgical procedure (which reliably produces moderate to severe pain) requires opioid treatment.
• Participant aged 2 years to less than 6 years has a pain level following a surgical procedure that reliably produces moderate to severe pain, for which the usual standard of care requires opioid treatment.
• Participant is alert, orientated, and able to follow commands and complete the post-operative required procedures.
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E.4 | Principal exclusion criteria |
• History of brain injury.
• Clinically relevant abnormal ECG.
• Clinically unstable vital signs and/or a saturation of oxygen saturation (SpO2) less than 93%. During surgery SpO2 may decrease <93%.
• Clinically relevant abnormal values for clinical chemistry, hematology, or urinalysis at enrollment.
• Body temperature above 38.5°C within 48 hours prior to dosing.
• Positive drugs of abuse test result.
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E.5 End points |
E.5.1 | Primary end point(s) |
Pharmacokinetic Profile of Serum Concentrations of Tapentadol and Tapentadol-O-glucuronide after a Single Dose of Tapentadol Oral Solution.
Non Compartmental Pharmacokinetic (PK) Parameter of Tapentadol and Tapentadol-O-glucuronide after a Single Dose of After a Single Dose of Tapentadol in Adolescent Participants (Age 12 to Less Than 18 Years). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Up to 15 hours after administration. |
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E.5.2 | Secondary end point(s) |
Pain Intensity Assessments Using the Visual Analog Scale (VAS) in Adolescent Participants (Aged 12 to Less Than 18 Years).
Pain Intensity Assessments Using the McGrath Color Analog Scale in Adolescent Participants and Older Children (Aged 6 to Less Than 18 Years).
Pain Intensity Assessments Using the Faces Pain Scale (Revised) in Children Age 3 to Less Than 12 Years.
Pain Intensity Assessment Using the Face, Legs, Activity, Cry, Consolability Scale in Young and Very Young Children (Age 2 to Less Than 6 Years).
Sum of Pain Intensity Differences (SPID) Over the 4 Hours After Dosing Derived From the Different Pain Scales and for All Age Groups.
Treatment Emergent Adverse Events by Intensity.
Intake of Additional Analgesic Medication During the Trial.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Pain Intensity Assessments in all age groups: 15 hours post dosing.
SPID: 4 hours post dosing.
Treatment Emergent Adverse Events: 48 hours post dosing.
Intake of additional analgesic medication: 15 hours post dosing. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
Will this trial be conducted at a single site globally?
| Yes |
E.8.4 | Will this trial be conducted at multiple sites globally? | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | Yes |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 4 |
E.8.9.2 | In all countries concerned by the trial days | 20 |