Pharmacokinetic Evaluation of MDZ028

Completed

• Conditions: Midazolam
• Interventions: Drug: Midazolam

• Registration Number: NCT03639428
• Lead Sponsor: Centre Hospitalier Universitaire, Amiens

Brief Summary

Plasma concentration data were collected from 37 paedriatic patients and 12 healthy adults recruited in a single dose, open-label phase II pharmacokinetic study and in a single dose, randomised, open-label two-peiod crossover bioavailability study, respectively. Data were analysed using non-linear mixed effect modeling.

Detailed Description

In the absence of a licensed formulation in many countries worldwide, ADV6209, an innovative 2mg/ml oral solution of midazolam containing cyclodextrin, has been developed for moderate sedation in paediatric patients. Population pharmacokinetics for ADV6209 is reported.

Plasma concentration data were collected from 37 paedriatic patients and 12 healthy adults recruited in a single dose, open-label phase II pharmacokinetic study and in a single dose, randomised, open-label two-peiod crossover bioavailability study, respectively. Data were analysed using non-linear mixed effect modeling. Plasma concentrations of midazolam were discribed by a two-compartement model. An additional one-compartement model was added for a α-hydroxymidazolam.

Study Timeline

• Study Start: 2011-06-23
• Primary Completion: 2017-11-30
• Study Completion: 2017-11-30
• Status Verified: 2018-08
• Study First Submitted: 2018-08-01
• Study First Submitted QC: 2018-08-20
• Last Update Submitted: 2018-08-20
• Study First Posted: 2018-08-21
• Last Update Posted: 2018-08-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 37

Inclusion Criteria

• Child (boy or girl) for whom surgery under general anesthesia is scheduled.
• Child aged 6 months to 17 years old.
• Child with a body mass index between the 3rd and 97th percentile.
• Child with ASA (American Society of Anesthesiology) status of I or II. Young girl of childbearing age (ie after puberty) and sexually active to have a result negative to the pregnancy test.
• Child whose parents / legal representative (s) agree to sign a consent form.
• Child whose opinion / agreement was / tried to be collected.
• Child and parents / legal representative (s) being ready and able to participate in the study, understanding and undertaking to respect the study procedures throughout the duration of the study.
• Child enrolled in a social security scheme.

Exclusion Criteria

• Child with midazolam allergy, benzodiazepine hypersensitivity or hypersensitivity known to one of the excipients of the formulation of the study.
• Child with respiratory disease (severe respiratory failure, acute respiratory depression).
• Child with heart disease.
• Child with gastrointestinal disorders that may affect absorption or gastroesophageal reflux.
• Child with growth disorders or abnormal weight-of-weight.
• Child taking Cytochrome P450 Interactions Within 60 Days of Inclusion in the study.
• Child with kidney failure, liver failure, history of myasthenia gravis, or neurological disease.
• Pregnant or lactating girl.
• Child who has a known human immunodeficiency virus (HIV) infection, or active hepatitis B, or active hepatitis C.
• A child who could present any condition that may prevent his participation in the study, according to the judgment of the investigator.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
2-11 years	Midazolam	17 children between 2 and 11 years received a single 0.3mg/kg midazolam dose of ADV6209
6 - 23 months	Midazolam	8 infants between 6 and 23 months received a single 0.3mg/kg midazolam dose of ADV6209
12-17 years	Midazolam	12 adolescents between 12 and 17 years received a single 0.3mg/kg midazolam dose of ADV6209

Primary Outcome Measures

Name	Time	Method
Pharmacokinetic analysis of the oral solution of midazolam (ADV6209)	1 day	The Aim of the study was to assess the pharmacokinetic analysis of an oral solution of midazolam (ADV6209) oral formulation in paedriatic patients from 6 months to 18 years ols in order to support dosing recommendations. All subjects received a single 0.3mg/kg midazolam dose of ADV6209, without exceeding a total dose of 10 mg.Population pharmacokinetic modelling was performed to characterise the concentration-time course of midazolam and its main active metabolite, and to evaluate the changes in clearance and volume of distibution in the different age groups.