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

Depressive Disorder Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01491035
• Other study ID #: 12708A
• Secondary ID: 2010-020170-42
• Status: Completed
• Phase: Phase 2
• First received: November 23, 2011
• Last updated: January 29, 2016
• Start date: April 2012
• Est. completion date: June 2015

Study information

• Verified date: January 2016
• Source: H. Lundbeck A/S
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical DevicesUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 48
• Est. completion date: June 2015
• Est. primary completion date: December 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 7 Years to 17 Years

Eligibility

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.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Anxiety Disorder
• Anxiety Disorders
• Depression
• Depressive Disorder
• Disease

Intervention

Drug:
• Vortioxetine
5 mg tablets for 14 days; orally; once daily
• Vortioxetine
10 mg tablets for 14 days (initial up-titration with 5 mg/day for 2 days); orally; once daily
• Vortioxetine
15 mg tablets for 14 days (initial up-titration with 5 and 10 mg/day for a total of 4 days); orally; once daily
• Vortioxetine
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

Locations

Country	Name	City	State
Germany	DE002	Berlin
Germany	DE001	Mainz
Germany	DE003	Ulm
United States	US002	Cincinnatti	Ohio
United States	US001	Cleveland	Ohio
United States	US003	Washington	District of Columbia
United States	US004	Wichita	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
H. Lundbeck A/S

Countries where clinical trial is conducted

United States,  Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No