Introduction Lisdexamfetamine is a centrally acting sympathomimetic. It is a prodrug of dexamphetamine, which is a central nervous system stimulant. The lisdexamfetamine parent compound does not bind to the sites responsible for the reuptake of noradrenaline and dopamine in vitro and is not thought to contribute to the pharmacological effects. After oral administration, lisdexamfetamine is rapidly absorbed from the gastrointestinal tract and hydrolysed primarily in whole blood to d-amphetamine, which is thought to be responsible for all of the drug’s activity. Amphetamines are non-catecholamine sympathomimetic amines with CNS stimulant activity. The mode of therapeutic action of amphetamine in Attention Deficit Hyperactivity Disorder (ADHD) is not fully established. However it is thought to be due to its ability to block the reuptake of noradrenaline and dopamine into the presynaptic neuron and increase the release of these monoamines into the extraneuronal space. The proposed indication is: Vyvanse is indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in: Children Adolescents Adults Clinical rationale ADHD is a common condition in childhood and has a significant burden through interference with regular activities and with socialisation. Lisdexamfetamine is proposed to have PK properties similar to a controlled release formulation. The advantage of such properties is that of once daily dosing with improved compliance and decreased stigmatisation. Formulation The formulation proposed for marketing is that used in the Pivotal studies. Contents of the clinical dossier of the clinical dossier The submission contained the following clinical information: Module 5 15 clinical pharmacology studies, including 13 that provided pharmacokinetic data and a further two that provided pharmacodynamic data. No population pharmacokinetic analyses. Nine pivotal efficacy/safety studies. Four other efficacy/safety studies. Three integrated summaries Module 1
Introduction Lisdexamfetamine is a centrally acting sympathomimetic. It is a prodrug of dexamphetamine, which is a central nervous system stimulant. The lisdexamfetamine parent compound does not bind to the sites responsible for the reuptake of noradrenaline and dopamine in vitro and is not thought to contribute to the pharmacological effects. After oral administration, lisdexamfetamine is rapidly absorbed from the gastrointestinal tract and hydrolysed primarily in whole blood to d-amphetamine, which is thought to be responsible for all of the drug’s activity. Amphetamines are non-catecholamine sympathomimetic amines with CNS stimulant activity. The mode of therapeutic action of amphetamine in Attention Deficit Hyperactivity Disorder (ADHD) is not fully established. However it is thought to be due to its ability to block the reuptake of noradrenaline and dopamine into the presynaptic neuron and increase the release of these monoamines into the extraneuronal space. The proposed indication is: Vyvanse is indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in: Children Adolescents Adults Clinical rationale ADHD is a common condition in childhood and has a significant burden through interference with regular activities and with socialisation. Lisdexamfetamine is proposed to have PK properties similar to a controlled release formulation. The advantage of such properties is that of once daily dosing with improved compliance and decreased stigmatisation. Formulation The formulation proposed for marketing is that used in the Pivotal studies. Contents of the clinical dossier of the clinical dossier The submission contained the following clinical information: Module 5 15 clinical pharmacology studies, including 13 that provided pharmacokinetic data and a further two that provided pharmacodynamic data. No population pharmacokinetic analyses. Nine pivotal efficacy/safety studies. Four other efficacy/safety studies. Three integrated summaries Module 1
auspar-lisdexamfetamine-dimesilate-131023-cer.docx