The Use of ADV6209 for Premedication in Pediatric Anesthesia
Condition: Preanesthetic Medication
Study type: Interventional
Phase: Phase 4

Summary: 
      To evaluate the effect of ADV6209, a new oral Midazolam formulation, on preoperative anxiety
      and sedation levels in paediatric anaesthesia Primary Objective: Sedation score (mYPAS) 30
      min after administration of the premedication drug Secondary Objective: Acceptance of
      anaesthesia mask induction Acceptance of oral administration of the premedication drug
    

Detailed description: 
      Premedication represents an important part in the perioperative management of children and is
      used to reduce pre-operative stress as well as to facilitate induction of inhaled
      anaesthesia. Midazolam is the drug most often used for premedication in infants and children
      because it provides good sedation, anxiolytic and amnestic effects and few side effects. Oral
      intake of the drug is the most preferred route of administration by paediatric patients,
      whereas the majority of existing oral Midazolam solutions involve the use of i.v. Midazolam
      formulation given orally, unregistered or off-label. Moreover i.v. Midazolam solutions are
      often not well accepted by children because of their bitter taste. Considering the lack of
      available oral medications for moderate sedation in children in most European countries,
      ADV6209, an innovative 0.2% (w/v) oral solution of Midazolam for children from six months of
      age, was developed. The formation of a γ-Cyclodextrin -Midazolam complex, representing a new
      chemical formula, was used to improve the solubility and the palatability of the Midazolam
      formulation. A pharmacokinetic (PK) study has been executed in adults, children and
      adolescents, whereas ADV6209 showed improvements to current extemporaneous oral solutions of
      midazolam (EOM) preparations in terms of taste and easiness of use while presenting a similar
      PK profile. Satisfying sedation, measured with the Observer Assessment of Alertness/Sedation
      Scale (OAA score / S≤17) was observed in 78.4% of paediatric patients 30 minutes after
      ADV6209 administration. Anxiety score (modified Yale Preoperative Anxiety Scale - mYPAS) was
      decreased by 18.3% on average over baseline, 30 minutes after ADV6209 with a more pronounced
      effect in the youngest children who were also the most anxious prior to administration of the
      drug. In general the treatment was well accepted by all children and did not induce more
      crying and nausea / vomiting than before Midazolam. ADV6209 seems a very promising
      premedication drug. It has been licensed by the EU regulatory authorities to become the first
      licensed paediatric sedative in the EU (September 2018). It may help to avoid unregistered
      and off label use of EOM. Consequently, we want to evaluate the efficacy and safety of
      ADV6209 on preoperative anxiety and sedation levels in paediatric anaesthesia in daily
      clinical routine in this randomized, controlled, double blinded study.
    

Intervention name(s): ADV6209 (=gamma-cyclodextrin-Midazolam); Midazolam
Intervention type(s): Drug; Drug
Intervention description(s): 30 min. before anesthesia children have to swallow the anxiolytic drug (ADV6209); 30 min. before anesthesia children have to swallow the anxiolytic drug Midazolam
Other intervention name(s): Ozalin (registered Tradename); Dormicum (Tradename)
Intervention MeSH terms: Midazolam
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: A controlled, randomized, double blinded study Study group 1 (40 children) ADV6209 0.25 mg/kg p.o. Study group 2 (40 children) Midazolam (in orange flavoured syrup) 0.25 mg/kg p.o.
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment