Investigation of Remimazolam in Children Undergoing Sedation for Medical Procedures

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

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

Study Overview

• Status: Active, not recruiting
• Conditions: Pediatric ALL
• Intervention / Treatment: Drug: Remimazolam

Detailed 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]).

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen, Denmark
    • Rigshospitalet
  • Odense, Denmark
    • Odense Universitetshospital
• United States
  • California
    • Palo Alto, California, United States, 94306
      • Stanford University
    • Sacramento, California, United States, 95817
      • University of California Davis Children's Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Boston Children's Hospital
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota Masonic Children's Hospital
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15224
      • University of Pittsburgh Medical Center - Children's Hospital of Pittsburgh
  • Texas
    • Houston, Texas, United States, 77030
      • Texas Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 second to 17 years (Child)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: All Patients; All paediatric patients undergoing diagnostic and/or therapeutic procedures	Drug: Remimazolam; Remimazolam for intravenous sedation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
Adequacy of sedation	Depth of sedation (assessed using Nurse Interpretation of Sedation Scale [NISS]) of patients over time	2 hours
Time to start of procedure	Time between initial administration of study drug and start of procedure	2 hours
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
Time to ready for discharge	Time between last dose of study drug, end of procedure and discharge readiness	2 hours
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
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
Safety: AEs	Incidence of treatment-emergent adverse events	4 days
Safety: emergence of delirium	Incidence of paediatric anaesthesia emergence delirium between end of procedure until fit for discharge	2 hours
Safety: need for ventilation	Incidence of use of any manual or mechanical ventilation	2 hours
Safety: need for reversal	Incidence of use of flumazenil for reversal of benzodiazepine effect	2 hours
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

Collaborators and Investigators

• Sponsor: Acacia Pharma Ltd
• Collaborators: Paion UK Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): November 15, 2021
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): October 1, 2027

Study Registration Dates

• First Submitted: April 14, 2021
• First Submitted That Met QC Criteria: April 17, 2021
• First Posted (Actual): April 20, 2021

Study Record Updates

• Last Update Posted (Estimated): July 1, 2025
• Last Update Submitted That Met QC Criteria: June 27, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Other Study ID Numbers: DA10030; CNS7056-026 (Other Identifier: PAION)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No