E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Paediatric procedural sedation |
|
E.1.1.1 | Medical condition in easily understood language |
Sedation for procedures in children |
|
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 | 23.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10083924 |
E.1.2 | Term | Sedation procedure |
E.1.2 | System Organ Class | 100000004865 |
|
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 assess the efficacy of IV remimazolam in inducing and maintaining suitable sedation levels for paediatric patients undergoing diagnostic and/or therapeutic procedures. |
|
E.2.2 | Secondary objectives of the trial |
To evaluate the onset and offset characteristics, the safety, and the PK of IV remimazolam in paediatric patients undergoing diagnostic and/or therapeutic procedures, and to establish dose levels for the different age groups. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Signed informed consent form and/or assent (if applicable) and willingness of patient and parent(s) to participate in the trial. • In European sites: Paediatric male or female patients, aged full term birth to <18 years scheduled to undergo a diagnostic or therapeutic procedure, which is medically indicated and independent from the trial. ◦ Patient aged <2 years must not be dosed in European sites until adequate supporting data are available from juvenile toxicity studies. • Maximum planned duration of procedure: 2 hours • ASA Physical Status I-III • Planned spontaneous breathing during sedation • A female who is of child bearing potential (i.e. after menarche) and sexually active must use a highly effective method of birth control during the trial period (from the time of consent until all specified observations are completed) • Negative pregnancy test at screening and on treatment day. Only needs to be performed once if screening is on the same day as the treatment day. |
|
E.4 | Principal exclusion criteria |
• Emergency procedures • Condition/procedure that requires planned airway control via endotracheal tube or LMA/IGEL insertion • Cranio-facial malformation, which would severely limit the possibilities for emergency airway rescue • Other abnormalities relating to the airway (including large tonsils and anatomical abnormalities of upper airway or lower airway) which may compromise emergency airway rescue • Known hypersensitivity to benzodiazepines, flumazenil, dextran or any of the ingredients of the IMP • Known paradoxical reactions to benzodiazepines • History of sleep apnoea • Active respiratory failure • Active neuromuscular disease • Active cardiac failure • Active hepatic failure • Pregnant or Breast-feeding females • Prohibited medication: ◦ Any investigational drug when taken within 30 days or less than 7 half-lives (whichever is longer) before Treatment Day. ◦ Any medication given for sedative purposes other than nitrous oxide and IMP on the Treatment Day ◦ (For full list of prohibited medication after randomisation please see Protocol) • Any patient judged by the Principal Investigator (PI) or Sub-Investigator to be inappropriate for the trial for any other reason |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Success of the procedure, defined as all of the following: • Completion of the procedure AND • No requirement for a rescue sedative medication AND • No requirement for more than the permitted bolus/infusion regimen |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
- After dosing of first 5 patients - Cohort 1, after dosing of at least 20 patients - Cohort 2, after dosing of at least 20 patients - Cohort 3, on an ongoing basis |
|
E.5.2 | Secondary end point(s) |
• Target depth of sedation achieved (target depth of sedation on the UMSS will be predefined by investigator per patient based on the procedure and patient needs before the procedure.) • Target range of sedation achieved during 80% of procedure duration (target range of sedation on the UMSS will be predefined by investigator per patient based on the procedure and patient needs before the procedure.) • Percentage of time within target range of sedation during the procedure • Adequacy of sedation, assessed as NISS over time. • Time to target sedation level and start of procedure after first dose of IMP (minutes) • Time to fully alert (defined as the first of three consecutive UMSS scores of 0) after end of procedure and end of last dose of IMP [minutes] • Signs of re-sedation i.e. after reaching a UMSS of 0 after end of procedure, whether a UMSS score of >0 was seen in the time until discharge. • Time to fit for discharge after end of procedure and end of last dose of IMP [minutes] • Success of the procedure, excluding cases where the procedure could not be completed for non sedative reasons. Defined as all of the following: - Completion of the procedure AND - No requirement for a rescue sedative medication AND - No requirement for more than the permitted bolus or infusion regimen
Secondary safety endpoints: • Treatment-emergent adverse events (TEAEs) after initiation of IMP • Vital signs (heart rate, blood pressure, body temperature and SpO2) • Need for any manual or mechanical ventilation, including mask ventilation without insertion of LMA/IGEL/ETT • Need for the reversal agent flumazenil, including reasons/indication for use • Emergence Delirium (paediatric anaesthesia emergence delirium scale) after end of procedure until fit for discharge. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
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) | Yes |
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 |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 3 |
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 |
|
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
|
|
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 | 3 |
E.8.9.1 | In the Member State concerned days | 28 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 13 |