Investigation of Remimazolam in Children Undergoing Sedation for Medical Procedures

Pediatric ALL Clinical Trial

Official title:

A Phase 2/3, Prospective, Open-label Trial Evaluating the Efficacy, Safety, and Pharmacokinetics of Remimazolam for Intravenous Sedation in Paediatric Patients Undergoing Diagnostic and/or Therapeutic Procedures

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04851717
• Other study ID #: DA10030
• Secondary ID: CNS7056-026
• Status: Active, not recruiting
• Phase: Phase 2/Phase 3
• Start date: November 15, 2021
• Est. completion date: December 2024

Study information

• Verified date: December 2022
• Source: Acacia Pharma Ltd
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To assess the efficacy of intravenous remimazolam in inducing and maintaining suitable sedation levels for paediatric patients undergoing diagnostic and/or therapeutic procedures

Description:

This trial is part of the European Paediatric Investigational Plan and the US Pediatric Study Plan and has been developed in line with guidance from the EMA Paediatric Committee and the US FDA.

The trial will commence with cohort 1 (aged ≥6 and <18 years) and proceed to lower age groups: cohort 2 (≥3 and <6 years); and, in European sites only, cohort 3 (full-term birth to <3 years). The Data Monitoring committee (DMC) may convene any time after at least half of the subjects in cohort 1 or 2 have completed the study, to review PK,safety and efficacy data. If there are no concerns, the DMC may recommend to initiate concurrent dosing in the next younger cohort (cohort 2 or 3) in parallel to dosing the remaining subjects in cohort 1 or 2 Dosing for cohort 3 will be predicted based on PK modelling as well as efficacy and safety outcomes of the older age groups. Enrolment of patients aged <2 years will not be permitted until supported by adequate juvenile toxicity data.

The trial will consist of three visits: Screening (Day -21 to day 1),Treatment (Day 1), and Follow-up (Day 4 [+3/-1 days]).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 100
• Est. completion date: December 2024
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 0 Years to 17 Years

Eligibility

Inclusion Criteria:

• Signed informed consent form and/or assent and willingness of patient and parent(s) to participate in the trial.

• In US sites: Paediatric male or female patients, aged =3 and <18 years scheduled to undergo a diagnostic or therapeutic procedure, which is medically indicated and independent from 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.

• 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 -

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 drug product

• Known paradoxical reactions to benzodiazepines

• History of sleep apnoea

• Active respiratory failure

• Active neuromuscular disease

• Active cardiac failure

• Active hepatic failure

• Breast feeding females

• Prohibited medication

• Any patient judged by the Principal Investigator (PI) or Sub-Investigator to be inappropriate for the trial for any other reason

Related Conditions & MeSH terms

• Pediatric ALL

Intervention

Drug:
• Remimazolam
Remimazolam for intravenous sedation

Locations

Country	Name	City	State
Denmark	Rigshospitalet	Copenhagen
Denmark	Odense Universitetshospital	Odense
United States	Boston Children's Hospital	Boston	Massachusetts
United States	Texas Children's Hospital	Houston	Texas
United States	University of Minnesota Masonic Children's Hospital	Minneapolis	Minnesota
United States	Stanford University	Palo Alto	California
United States	University of Pittsburgh Medical Center - Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania
United States	University of California Davis Children's Hospital	Sacramento	California

Sponsors (2)

Lead Sponsor	Collaborator
Acacia Pharma Ltd	Paion UK Ltd.

Countries where clinical trial is conducted

United States,  Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Success of the procedure	Success of the procedure defined as: Completion of the procedure AND no requirement for rescue sedative medication AND no requirement for more than the permitted bolus or infusion regimen	2 hours
Secondary	Target depth of sedation achieved	Proportion of patients achieving predefined target depth of sedation (assessed using University of Michigan Sedation Score [UMSS]) during procedure	2 hours
Secondary	Target range of sedation achieved during 80% of procedure duration	Proportion of patients in whom predefined target range of sedation (assessed using University of Michigan Sedation Score [UMSS]) was achieved during at least 80% of procedure duration	2 hours
Secondary	Percentage of time within target range of sedation	Percentage of time spent by patients within predefined target range of sedation (assessed using University of Michigan Sedation Score [UMSS]) during procedure	2 hours
Secondary	Adequacy of sedation	Depth of sedation (assessed using Nurse Interpretation of Sedation Scale [NISS]) of patients over time	2 hours
Secondary	Time to start of procedure	Time between initial administration of study drug and start of procedure	2 hours
Secondary	Time to fully alert	Time between last dose of study drug, end of procedure and full alertness, defined as the first of three consecutive sedation scores showing no sedation	2 hours
Secondary	Time to ready for discharge	Time between last dose of study drug, end of procedure and discharge readiness	2 hours
Secondary	Signs of re-sedation	Occurrence, after reaching a University of Michigan Sedation Score (UMSS) of 0 after end of procedure, of a UMSS greater than zero	2 hours
Secondary	Procedure success excluding cases where the procedure could not be completed for non sedative reasons	Success of the procedure defined as: Completion of the procedure AND no requirement for rescue sedative medication AND no requirement for more than the permitted bolus or infusion regimen; excluding any patients where procedure was not completed for reasons other than failure of sedation	2 hours
Secondary	Safety: AEs	Incidence of treatment-emergent adverse events	4 days
Secondary	Safety: emergence of delirium	Incidence of paediatric anaesthesia emergence delirium between end of procedure until fit for discharge	2 hours
Secondary	Safety: need for ventilation	Incidence of use of any manual or mechanical ventilation	2 hours
Secondary	Safety: need for reversal	Incidence of use of flumazenil for reversal of benzodiazepine effect	2 hours
Secondary	PK: assessment of plasma concentration-time relationship	Graphical description of plasma concentration over time and comparison to predicted concentration-time relationship as calculated from existing pharmacokinetic/pharmacodynamic model	3.5 hours