E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
The management of acute postoperative pain in hospitalized paediatric patients. |
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E.1.1.1 | Medical condition in easily understood language |
A study to look at Tapentadol Oral Solution in Children and Adolescents in pain after Surgery
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E.1.1.2 | Therapeutic area | Diseases [C] - Symptoms and general pathology [C23] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.0 |
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 | 17.0 |
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 |
Efficacy of tapentadol oral solution, based on the total amount of supplemental opioid analgesic medication (morphine equivalents in mg/kg body weight) used within the first 24 hours after first IMP intake. |
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E.2.2 | Secondary objectives of the trial |
To assess the efficacy of tapentadol oral solution using multiple subjective and objective measures of the subject’s response to treatment. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Informed consent, and if applicable assent, given according to local regulations.
2. Male or female subject aged from birth to less than 18 years.
3. A female subject must be pre-menarchal, or surgically incapable of childbearing, or sexually abstinent, or if a female subject is sexually active, then she must be practicing an effective method of birth control (e.g., prescription hormonal contraceptives, intra-uterine devices used according to the product’s instruction, double-barrier methods) before trial entry and throughout the trial.
4. female subject must have a negative urine pregnancy test if aged 12 years or older, or is post-menarchal, or is sexually active.
5. Subject has undergone surgery (other than brain surgery or gastrointestinal surgery expected to affect the absorption of tapentadol [in the investigator’s judgment]) that, in the investigator’s opinion, would reliably produce moderate to severe pain requiring opioid treatment for at least 24 hours after allocation/randomization to IMP.
6. Subject has received post-operative morphine or hydromorphone by NCA/PCA, with or without a background infusion of the same opioid, according to standard of care prior to allocation/randomization to IMP and subject is expected to require this morphine or hydromorphone by NCA/PCA after starting IMP.
7. Subject is able to tolerate liquids at the time of allocation/randomization to IMP. |
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E.4 | Principal exclusion criteria |
1. Subject, parent or the legal representative is an employee of the investigator or trial site, with direct involvement in the proposed trial or other trials under the direction of that investigator or trial site, or family member of the employees or the investigator.
2. Subject has been previously exposed to tapentadol.
3. Subject has received an experimental drug or used an experimental medical device within 28 days before allocation/randomization to IMP, or within a period less than 10 times the drug’s half-life,
whichever is longer.
4. Subject has a history or current condition of any one of the following:
• Non-febrile seizure disorder.
• Epilepsy.
• Serotonin syndrome.
• Traumatic or hypoxic brain injury, brain contusion, stroke, transient ischemic attack, intracranial hematoma, post-traumatic amnesia, brain neoplasm, or episode(s) of unconsciousness of more than 24 hours.
5. Subject has a history or current condition of any one of the following:
• Moderate to severe renal or hepatic impairment.
• Abnormal pulmonary function or clinically relevant respiratory disease (e.g., acute or severe bronchial asthma, hypercapnia).
6. Subject has a concomitant disease or disorder (e.g., endocrine, metabolic, neurological, psychiatric, infection, febrile seizure, paralytic ileus) that in the opinion of the investigator may affect or compromise subject safety during the trial participation.
7. Subject has history of suicidal ideation or behavior.
8. Subject is obese, e.g., BMI above the 97th percentile for children based on the World Health Organization growth charts.
9. Subject has a clinically relevant history of hypersensitivity, allergy, or contraindication to the supplemental opioid analgesic medication or tapentadol, or the excipients, or naloxone.
10. Subject is not able to understand and comply with the protocol as appropriate for the age of the subject.
11. Subject has a history of alcohol and/or substance abuse in the investigator’s judgment based on subject’s history and physical examination.
12. Subject is taking forbidden concomitant medication.
13. Subject has received a long-acting opioid for the treatment of pain following surgery within 6 hours of allocation/randomization to IMP.
14. Subject has clinically relevant (in the investigator’s judgment) abnormal values for clinical chemistry or hematology (local laboratory sample taken after surgery).
A subject is excluded if the:
• Aspartate transaminase or alanine transaminase is >3-times upper limit of normal.
• Total bilirubin is >2-times upper limit of normal (except if the cause is due to Gilbert’s syndrome).
• Glomerular filtration rate <60 mL/min (calculated according to a formula that is appropriate for the respective age group).
15. Subject has:
• Clinically relevant abnormal ECG.
• Signs of pre-excitation syndrome.
• Brugada’s syndrome.
• QT or QTc interval >470 ms for children aged 6 years to less than 18 years old.
• QT or QTc interval >460 ms for children aged from birth to less than 6 years old.
16. Peri- or post-operative analgesia supplied by a continuous regional technique (i.e., nerve block) or subject controlled epidural analgesia that was terminated less than 6 hours before allocation/randomization to IMP.
17. Subject has post-operative clinically unstable systolic and diastolic blood pressure, heart rate, respiratory depression, or clinically unstable upper or lower airway conditions (in the investigator’s
judgment), or a saturation of peripheral oxygen (SpO2) <92% at the time of randomization (allocation/randomization to IMP). |
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E.5 End points |
E.5.1 | Primary end point(s) |
The total amount of supplemental opioid analgesic medication (morphine equivalents in mg/kg body weight) used after first IMP intake. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
EU: 24 hours
US: 12 hours |
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E.5.2 | Secondary end point(s) |
1. The total amount of supplemental opioid analgesic medication received during treatment with IMP over a maximum period of 48 hours after the first dose of IMP.
2. The total amount of non-opioid analgesics used.
3. Palatability and acceptability of the IMP.
4. Changes from baseline in pain intensity.
5. Clinician Global Impression of Change.
6. Patient Global Impression of Change.
7. Time to first and time to second NCA/PCA after first dose of IMP.
8. Time to first dose of IMP until IMP treatment discontinuation due to lack of efficacy.
9. Safety
• Percentage of subjects with TEAEs.
• Percentages of subjects who develop abnormal:
− Vital signs.
− Laboratory parameters.
− 12-lead ECG parameters.
• Changes from baseline in vital signs parameters.
• Changes from baseline in safety laboratory parameters.
• Changes from baseline in 12-lead ECG parameters.
• Percentage of subjects discontinuing the trial due to TEAEs and drug-related adverse events.
• Suicidal ideation/behavior in subjects aged 6 years or older using the C-SSRS scores before IMP and at the end of the trial. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Efficacy endpoints:
12 hours
24 hours
48 hours
Safety endpoints:
up to Day 14 |
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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 | Yes |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
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 | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 30 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Austria |
Croatia |
France |
Germany |
Poland |
Spain |
Sweden |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
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.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 1 |