Clinical trial NCT04851717: Investigation of Remimazolam in Children Undergoing Sedation for Medical Procedures
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: Pediatric ALL
Lead sponsor: Acacia Pharma Ltd
Sponsor class: INDUSTRY
Collaborators: name: Paion UK Ltd.
First posted: 2021-04-20
Enrollment: 100
Sex: ALL
Minimum age (years): 0
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: A Phase 2/3 prospective, open-label trial
Primary purpose: SUPPORTIVE_CARE

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

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 \[+3/-1 days\]).

Eligibility criteria: 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

Primary outcomes:
measure: Success of the procedure
timeFrame: 2 hours
Secondary outcomes:
measure: Target depth of sedation achieved
timeFrame: 2 hours
measure: Target range of sedation achieved during 80% of procedure duration
timeFrame: 2 hours
measure: Percentage of time within target range of sedation
timeFrame: 2 hours
measure: Adequacy of sedation
timeFrame: 2 hours
measure: Time to start of procedure
timeFrame: 2 hours
measure: Time to fully alert
timeFrame: 2 hours
measure: Time to ready for discharge
timeFrame: 2 hours
measure: Signs of re-sedation
timeFrame: 2 hours
measure: Procedure success excluding cases where the procedure could not be completed for non sedative reasons
timeFrame: 2 hours
measure: Safety: AEs
timeFrame: 4 days
measure: Safety: emergence of delirium
timeFrame: 2 hours
measure: Safety: need for ventilation
timeFrame: 2 hours
measure: Safety: need for reversal
timeFrame: 2 hours
measure: PK: assessment of plasma concentration-time relationship
timeFrame: 3.5 hours
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: Sacramento
country: United States
facility: University of California Davis Children's Hospital
state: California
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Minneapolis
country: United States
facility: University of Minnesota Masonic Children's Hospital
state: Minnesota
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center - Children's Hospital of Pittsburgh
state: Pennsylvania
city: Houston
country: United States
facility: Texas Children's Hospital
state: Texas
city: Copenhagen
country: Denmark
facility: Rigshospitalet
city: Odense
country: Denmark
facility: Odense Universitetshospital
Study officials:
References: