Pharmacokinetics and Tolerability of Vortioxetine (Lu AA21004) in Child and Adolescent Patients With Depressive or Anxiety Disorder

Study Overview
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Brief Summary
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The objective of the study is to evaluate the pharmacokinetics of vortioxetine and its metabolites in connection with multiple oral dosing in child and adolescent patients with a DSM-IV-TR diagnosis of Depressive or Anxiety Disorder

Detailed Description
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The study will be conducted in the US and in Europe and will include paediatric patients diagnosed with depressive or anxiety disorders of two age populations; children aged 7-11 years and adolescents of the age 12-17 years. It is an open study to allow pharmacokinetic (PK) sampling of all patients and four dose levels will be tested. Following lower initial doses for 2 to 6 days, the patients will be treated once daily at the assigned dose levels for 14 days, and it is expected that patients may benefit from treatment during this period. As the treatment duration is not sufficient according to treatment guidelines, if judged or indicated by the investigator, the patients are offered to continue in an extension treatment of up to six months to allow possibility for therapeutic satisfaction. Preferably, the cohorts will be dosed in the following order: AC1, AC2, CC1, AC3, CC2, AC4, CC3, and CC4. An external data safety monitoring board (DSMB) will be established to evaluate safety, tolerability and preliminary PK data from the dosed cohort(s) prior to any dosing of subsequent cohort (s). The dose regimen may be adjusted based on the recommendation of the DSMB. Adolescents will be exposed to a certain dose of vortioxetine before children receive the same dose.

Official Title
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An Open-label Study Evaluating the Pharmacokinetics and Tolerability of [Vortioxetine] Lu AA21004 in Connection With Multiple Oral Dosing of [Vortioxetine] Lu AA21004 in Child and Adolescent Patients With a DSM-IV Diagnosis of Depressive or Anxiety Disorder

Conditions
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Depressive Disorder, Anxiety Disorder

Intervention / Treatment
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* Drug: Vortioxetine
* Drug: Vortioxetine
* Drug: Vortioxetine
* Drug: Vortioxetine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with a DSM-IV-TR diagnosis of Depressive or Anxiety Disorder. The patient and parent(s)/legal representative(s) are able to comprehend and satisfactorily comply with the protocol requirements. Treatment with antidepressant therapy is warranted, as judged by the investigator. Exclusion Criteria: The patient is pregnant or breast-feeding. The patient presents or has a history of an Axis I (DSM-IV-TR) diagnosis of Bipolar Disorder, Post Traumatic Stress Disorder (PTSD), Autism, Pervasive Developmental Disorder (PDD), Obsessive Compulsive Disorder (OCD) or Schizophrenia or Schizoaffective Disorder. The patient has not maintained a stable dose of a methylphenidate or amphetamine for their treatment of attention-deficit/hyperactivity disorder (ADHD) for a minimum of 4 weeks prior to the study treatment. The patient has a known mental retardation, or clinical evidence or known social or school history indicative of mental retardation. The patient is at significant risk of committing suicide based on history (for example previous suicide attempt) or according to the investigator's experience, or based on active suicidal ideation, intent or plan, item 4 or 5 of the Columbia-Suicide Severity Rating Scale (C-SSRS). The subject has any concurrent illness that may affect the particular target or absorption, distribution, and elimination of the investigational medicinal product (IMP). The patient meets DSM-IV-TR criteria for any psychoactive substance or alcohol use disorder. Other inclusion and exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 7 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort CC1, 6 children<br> | Drug: Vortioxetine<br>* 5 mg tablets for 14 days; orally; once daily<br>* Other names: Brintellix;|
| Experimental: Cohort CC2, 6 children<br> | Drug: Vortioxetine<br>* 10 mg tablets for 14 days (initial up-titration with 5 mg/day for 2 days); orally; once daily<br>* Other names: Brintellix;|
| Experimental: Cohort CC3, 6 children<br> | Drug: Vortioxetine<br>* 15 mg tablets for 14 days (initial up-titration with 5 and 10 mg/day for a total of 4 days); orally; once daily<br>* Other names: Brintellix;|
| Experimental: Cohort CC4, 6 children<br> | Drug: Vortioxetine<br>* 20 mg tablets for 14 days (initial up-titration with 5, 10, and 15 mg/day for a total of 6 days); orally; once daily<br>* Other names: Brintellix;|
| Experimental: Cohort AC1, 6 adolescents<br> | Drug: Vortioxetine<br>* 5 mg tablets for 14 days; orally; once daily<br>* Other names: Brintellix;|
| Experimental: Cohort AC2, 6 adolescents<br> | Drug: Vortioxetine<br>* 10 mg tablets for 14 days (initial up-titration with 5 mg/day for 2 days); orally; once daily<br>* Other names: Brintellix;|
| Experimental: Cohort AC3, 6 adolescents<br> | Drug: Vortioxetine<br>* 15 mg tablets for 14 days (initial up-titration with 5 and 10 mg/day for a total of 4 days); orally; once daily<br>* Other names: Brintellix;|
| Experimental: Cohort AC4, 6 adolescents<br> | Drug: Vortioxetine<br>* 20 mg tablets for 14 days (initial up-titration with 5, 10, and 15 mg/day for a total of 6 days); orally; once daily<br>* Other names: Brintellix;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax of Vortioxetine | Maximum plasma concentration of vortioxetine | Pre-dose and 1, 3, 5, 8, 12 and 24 hours post-dose on Day 14, 16, 18, or 20, depending on assigned dose level | 
| AUC(0-24h) of Vortioxetine | Area under the vortioxetine plasma concentration-time curve from 0 to 24 hours | Pre-dose and 1, 3, 5, 8, 12 and 24 hours post-dose on Day 14, 16, 18 or 20, depending on assigned dose level | 
| t½ of Vortioxetine | Half-life of vortioxetine in plasma | Pre-dose and 1, 3, 5, 8, 12 and 24 hours post-dose on Day 14, 16, 18 or 20, depending on assigned dose level | 
| Cmax of Lu AA34443 | Maximum plasma concentration of the major, inactive metabolite Lu AA34443 | Pre-dose and 1, 3, 5, 8, 12 and 24 hours post-dose on Day 14, 16, 18, or 20, depending on assigned dose level | 
| AUC(0-24h) of Lu AA34443 | Area under the plasma concentration-time curve from 0 to 24 hours for the major, inactive metabolite Lu AA34443 | Pre-dose and 1, 3, 5, 8, 12 and 24 hours post-dose on Day 14, 16, 18 or 20, depending on assigned dose level | 
| t½ of Lu AA34443 | Half-life of the major, inactive metabolite Lu AA34443 in plasma | Pre-dose and 1, 3, 5, 8, 12 and 24 hours post-dose on Day 14, 16, 18 or 20, depending on assigned dose level | 
| Oral Clearance (CL/F) of Vortioxetine | Oral clearance expressed as a function of bioavailability | Pre-dose and 1, 3, 5, 8, 12 and 24 hours post-dose on Day 14, 16, 18 or 20, depending on assigned dose level | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Children, Adolescents, Pharmacokinetic, Pharmacodynamic