E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
acute pain in paediatric patients |
|
E.1.1.1 | Medical condition in easily understood language |
|
E.1.1.2 | Therapeutic area | Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Anesthesia and Analgesia [E03] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10066714 |
E.1.2 | Term | Acute pain |
E.1.2 | System Organ Class | 100000004867 |
|
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 efficacy of PENTHROX® (methoxyflurane) for the treatment of acute pain in paediatric patients presenting to an Emergency Department (ED) with minor trauma |
|
E.2.2 | Secondary objectives of the trial |
To evaluate the safety of PENTHROX® (methoxyflurane) for the treatment of acute pain in paediatric patients presenting to an ED with minor trauma. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Patients aged 6 to less than 18 years.
2.Attending ED following minor trauma.
3.Evidence of signed and dated informed consent/assent document indicating that the patient (and/or a parent/legal guardian) has been informed of all pertinent aspects of the study.
4.Pain scores 60 to 80 mm as measured using VAS or 6 to 8 using Wong Baker FACES® Pain Rating scale.
|
|
E.4 | Principal exclusion criteria |
1.Critical, life- or limb-threatening condition requiring immediate management.
2.Open fractures.
3.Patients with any other clinical condition that may, in the opinion of the Investigator, impact the patient’s ability to participate in the study, or the study results.
4.Patients deemed not cognitively capable of effectively self-administering the study drug using the PENTHROX® inhaler.
5. Treatment with any analgesic agent within 5 hours prior to presentation to ED, except Entonox (50% nitrous oxide and 50% oxygen mixture) which is prohibited within 30 minutes prior to arrival at ED, diclofenac which is prohibited within 8 hours prior to presentation to ED or oral morphine which is prohibited within 10 hours prior to presentation to ED.
6.Patients with chronic pain.
7.Patients having received an IMP in the preceding 3 months.
8.Known pregnancy or breastfeeding females.
9.Personal or familial hypersensitivity to PENTHROX® or any fluorinated anaesthetics.
10.Patients requiring oxygen therapy.
11.Patients with known or genetic susceptibility to malignant hyperthermia or a history of severe adverse reactions in either patient or relatives.
12.Clinically evident respiratory depression.
13.Previous use of methoxyflurane (including as an IMP).
14.History of signs of liver damage including after previous PENTHROX® (methoxyflurane) use or halogenated hydrocarbon anaesthesia.
15.Known significant renal impairment.
16.Altered level of consciousness due to any cause including head injury, drugs, or alcohol.
17.Known significant cardiovascular disease (e.g., pathological arrhythmia).
18.Inability to participate in telephonic follow-up on (Day 14 ± 2 days) as per study requirement.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
•Difference in pain intensity between active drug and placebo as measured by VAS from baseline to 15 minutes after the commencement of treatment |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
15 minutes after commencement of treatment |
|
E.5.2 | Secondary end point(s) |
•Responder analysis – number and percentage of responders, who achieve 30% reduction in VAS score compared to baseline, at 15 minutes.
•Responder analysis – exploratory: number and percentage of responders who achieve 30% reduction in VAS score compared to baseline at 5, 10 and 20 minutes.
•Change in pain intensity as measured using VAS from baseline to 5, 10, 15, 20 and 30 minutes, followed by a 30-minute interval thereafter until the point of ED discharge/in-patient admission decision.
•Rescue medication requested within 20 minutes of start of treatment and any time during treatment.
•The time to request for rescue medication.
•The time to first pain relief.
•The number of inhalations taken before first pain relief and whether the patient covered the hole in the Inhaler during inhalation.
•Global medication performance assessment by patient, clinician and research nurse: 0 = poor to 4 = excellent, measured after completion of treatment.
•Evaluation of adverse events (AEs) experienced during treatment, not associated with the underlying minor trauma.
•Evaluation for any change in vital signs and sedation score during treatment.
•Evaluation of AEs at 14 ± 2 days following ED discharge using follow-up questionnaire that includes high output nephrotoxicity.
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
As specified within the descriptions of the endpoints above. |
|
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 | No |
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
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 10 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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
|
once the last patient had had their telephonic follow up on Day 14+/2 |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 12 |
E.8.9.1 | In the Member State concerned days | 14 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 12 |
E.8.9.2 | In all countries concerned by the trial days | 14 |