Pharmacokinetic Evaluation of MDZ028 (MIDAZOLAM)

Pharmacokinetic Evaluation of MDZ028 After Single Administration of a New Oral Form, at the Time of Anesthetic Premedication in Children.

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.

Study Overview

• Status: Completed
• Conditions: Midazolam
• Intervention / Treatment: Drug: Midazolam

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 Type: Observational
• Enrollment (Actual): 37

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

The planned enrollment is 36 children, stratified in two groups: 24 children between 6 months and 11 years, and 12 children between 12 and 17 years. Age is considered in years past by the date of inclusion. Children aged between 6 months and 11 years old should be homogenous in both age groups 6-23 months and 2-11 years. For example, at least 4 children in the 6-23 month age group will be recruited.

Children likely to be included will be hospitalized in the pediatric surgery department at Amiens University Hospital.

Children who will be included in this study will not be able to participate in another study within 3 months of their inclusion in this study.

Description

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 Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
6 - 23 months; 8 infants between 6 and 23 months received a single 0.3mg/kg midazolam dose of ADV6209	Drug: Midazolam; All subjects received a sigle 0.3mg/kg midazolam dose os ADV6209; Other Names: midazolam dose of ADV6209
2-11 years; 17 children between 2 and 11 years received a single 0.3mg/kg midazolam dose of ADV6209	Drug: Midazolam; All subjects received a sigle 0.3mg/kg midazolam dose os ADV6209; Other Names: midazolam dose of ADV6209
12-17 years; 12 adolescents between 12 and 17 years received a single 0.3mg/kg midazolam dose of ADV6209	Drug: Midazolam; All subjects received a sigle 0.3mg/kg midazolam dose os ADV6209; Other Names: midazolam dose of ADV6209

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic analysis of the oral solution of midazolam (ADV6209)	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.	1 day

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire, Amiens

Study record dates

Study Major Dates

• Study Start (Actual): June 23, 2011
• Primary Completion (Actual): November 30, 2017
• Study Completion (Actual): November 30, 2017

Study Registration Dates

• First Submitted: August 1, 2018
• First Submitted That Met QC Criteria: August 20, 2018
• First Posted (Actual): August 21, 2018

Study Record Updates

• Last Update Posted (Actual): August 21, 2018
• Last Update Submitted That Met QC Criteria: August 20, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: pharmacokinetics; child; cyclodextrin; moderate sedation
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Midazolam
• Other Study ID Numbers: PI10-PR-DUPONT

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: No
• Studies a U.S. FDA-regulated device product: No