E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Sudden unexpected death in epilepsy (SUDEP) primarily affects young adults with drug-resistant epilepsy |
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E.1.1.1 | Medical condition in easily understood language |
Sudden unexpected death in epilepsy (SUDEP) primarily affects young adults with drug-resistant epilepsy |
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E.1.1.2 | Therapeutic area | Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Therapeutic techniques [E02] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10065336 |
E.1.2 | Term | Partial epilepsy |
E.1.2 | System Organ Class | 100000004852 |
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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 |
The main objective of the study is to evaluate the efficacy of 0.4 mg intravenous naloxone, versus placebo, administered in the immediate aftermath of a GTCS, in reducing the severity of the postictal central respiratory dysfunction occurring after the end of the seizure, as measured by pulse oximetry. |
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E.2.2 | Secondary objectives of the trial |
Assess the impact of naloxone on respiratory parameters such as the frequency of apneas (> 10 seconds) occurring after the end of the seizure.
Assess the impact of naloxone on 02 administration requirement and on cardiorespiratory rescue procedure requirement after the end of the seizure.
Assess the impact of naloxone on the postictal generalized EEG suppression, the duration of which is correlated with the risk of SUDEP, and the severity of which could also result from a seizure-related release of endogenous opioids.
Assess the impact of naloxone on the duration of the postictal coma following a GTCS, and the time required by the patient to recover preictal clinical condition. In the future, this clinical benefit might be enough significant to justify the systematic use of naloxone after GTCS in inpatients
Assess the frequency and severity of adverse events related to the treatment with naloxone, such as increased posictal pain and/or early recurrence of GCTS.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
For inclusion
Adult patient (≥ 18 years) suffering from drug-resistant partial epilepsy
Patient undergoing long-term video-EEG monitoring in one of the participating centre to record and characterize its seizure
Patient who gave its written informed consent to participate to the study
For randomization
Patient who suffers a secondary generalized tonic-clonic seizure during the long-term video-EEG monitoring while being supervised by a nurse or a physician
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E.4 | Principal exclusion criteria |
Age < 18 years
Pregnant or breastfeeding women
Hypersensitivity to naloxone
History of severe heart disease (myocardial infarction, heart failure disorder, arrhythmia
severe hypertension)
Ongoing opioïd treatment, including both pure agonists and partial agonists
Addiction to opioïds, heroin, or any similar substance
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E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of patients whose oxygen saturation (SpO2) is <90% during at least 5 seconds between 30 seconds and 5 minutes after onset of intravenous injection of the study drug in the immediate aftermath of a GTCS |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
-Other respiratory parameters
-Proportion of patients whose SpO2 is <85%, 80% and 70% during at least 5 seconds between 30 seconds and 5 minutes after onset of intravenous injection of the study drug in the immediate aftermath of a GTCS.
-Desaturation nadir between 30 seconds and 5 minutes after onset of intravenous injection of the study drug in the immediate aftermath of a GTCS
-Number of patients who show postictal apnea, defined as the absence of chest expansion during a period > 10 seconds between 30 seconds and 5 minutes after onset of intravenous injection of the study drug in the immediate aftermath of a GTCS.
-Number of patients in whom 02 administration is required within the ten minutes following the end of a GTCS.
-Number of patients in whom cardiorespiratory rescue procedure is required within the ten minutes following the end of a GTCS
-Total duration of the postictal generalized EEG suppression, defined as lack of detectable EEG activity >10 mV in amplitude on all leads.
-Total duration of the postictal coma, defined as the delay between the end of the seizure and the recovery of consciousness assessed by the ability to meet one single verbal command (handshake).
-Report of adverse events observed throughout the study
-Assessment of pain, using a visual analog scale, immediately after the recovery of consciousness following the postictal coma.
-Number of patients who have a second GCTS within 120 minutes after the intravenous injection.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | 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 | 14 |
E.8.5 | The trial involves multiple Member States | No |
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 | 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.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |