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

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

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

Study Overview

• Status: Completed
• Conditions: Depressive Disorder; Anxiety Disorder
• Intervention / Treatment: Drug: Vortioxetine; Drug: Vortioxetine; Drug: Vortioxetine; Drug: Vortioxetine

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 10249
    • DE002
  • Mainz, Germany, 55122
    • DE001
  • Ulm, Germany, 89075
    • DE003
• United States
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • US003
  • Kansas
    • Wichita, Kansas, United States, 67214
      • US004
  • Ohio
    • Cincinnatti, Ohio, United States, 45219
      • US002
    • Cleveland, Ohio, United States, 44106
      • US001

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years to 15 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort CC1, 6 children	Drug: Vortioxetine; 5 mg tablets for 14 days; orally; once daily; Other Names: Brintellix; Drug: Vortioxetine; 10 mg tablets for 14 days (initial up-titration with 5 mg/day for 2 days); orally; once daily; Other Names: Brintellix; Drug: 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; Other Names: Brintellix; Drug: 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; Other Names: Brintellix
Experimental: Cohort CC2, 6 children	Drug: Vortioxetine; 5 mg tablets for 14 days; orally; once daily; Other Names: Brintellix; Drug: Vortioxetine; 10 mg tablets for 14 days (initial up-titration with 5 mg/day for 2 days); orally; once daily; Other Names: Brintellix; Drug: 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; Other Names: Brintellix; Drug: 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; Other Names: Brintellix
Experimental: Cohort CC3, 6 children	Drug: Vortioxetine; 5 mg tablets for 14 days; orally; once daily; Other Names: Brintellix; Drug: Vortioxetine; 10 mg tablets for 14 days (initial up-titration with 5 mg/day for 2 days); orally; once daily; Other Names: Brintellix; Drug: 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; Other Names: Brintellix; Drug: 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; Other Names: Brintellix
Experimental: Cohort CC4, 6 children	Drug: Vortioxetine; 5 mg tablets for 14 days; orally; once daily; Other Names: Brintellix; Drug: Vortioxetine; 10 mg tablets for 14 days (initial up-titration with 5 mg/day for 2 days); orally; once daily; Other Names: Brintellix; Drug: 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; Other Names: Brintellix; Drug: 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; Other Names: Brintellix
Experimental: Cohort AC1, 6 adolescents	Drug: Vortioxetine; 5 mg tablets for 14 days; orally; once daily; Other Names: Brintellix; Drug: Vortioxetine; 10 mg tablets for 14 days (initial up-titration with 5 mg/day for 2 days); orally; once daily; Other Names: Brintellix; Drug: 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; Other Names: Brintellix; Drug: 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; Other Names: Brintellix
Experimental: Cohort AC2, 6 adolescents	Drug: Vortioxetine; 5 mg tablets for 14 days; orally; once daily; Other Names: Brintellix; Drug: Vortioxetine; 10 mg tablets for 14 days (initial up-titration with 5 mg/day for 2 days); orally; once daily; Other Names: Brintellix; Drug: 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; Other Names: Brintellix; Drug: 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; Other Names: Brintellix
Experimental: Cohort AC3, 6 adolescents	Drug: Vortioxetine; 5 mg tablets for 14 days; orally; once daily; Other Names: Brintellix; Drug: Vortioxetine; 10 mg tablets for 14 days (initial up-titration with 5 mg/day for 2 days); orally; once daily; Other Names: Brintellix; Drug: 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; Other Names: Brintellix; Drug: 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; Other Names: Brintellix
Experimental: Cohort AC4, 6 adolescents	Drug: Vortioxetine; 5 mg tablets for 14 days; orally; once daily; Other Names: Brintellix; Drug: Vortioxetine; 10 mg tablets for 14 days (initial up-titration with 5 mg/day for 2 days); orally; once daily; Other Names: Brintellix; Drug: 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; Other Names: Brintellix; Drug: 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; Other Names: Brintellix

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: H. Lundbeck A/S

Publications and helpful links

General Publications

• Findling RL, Robb AS, DelBello MP, Huss M, McNamara NK, Sarkis EH, Scheffer RE, Poulsen LH, Chen G, Lemming OM, Auby P. A 6-Month Open-Label Extension Study of Vortioxetine in Pediatric Patients with Depressive or Anxiety Disorders. J Child Adolesc Psychopharmacol. 2018 Feb;28(1):47-54. doi: 10.1089/cap.2017.0047. Epub 2017 Oct 16.

Helpful Links

• EMA EudraCT Results: 2010-020170-42

Study record dates

Study Major Dates

• Study Start: April 1, 2012
• Primary Completion (Actual): December 1, 2014
• Study Completion (Actual): June 1, 2015

Study Registration Dates

• First Submitted: November 23, 2011
• First Submitted That Met QC Criteria: December 9, 2011
• First Posted (Estimate): December 13, 2011

Study Record Updates

• Last Update Posted (Actual): March 16, 2017
• Last Update Submitted That Met QC Criteria: February 8, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Keywords: Adolescents; Children; Pharmacokinetic; Pharmacodynamic
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Mood Disorders; Depressive Disorder; Disease; Anxiety Disorders; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Tranquilizing Agents; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Serotonin 5-HT1 Receptor Agonists; Serotonin Receptor Agonists; Serotonin Antagonists; Anti-Anxiety Agents; Serotonin 5-HT3 Receptor Antagonists; Vortioxetine
• Other Study ID Numbers: 12708A; 2010-020170-42 (EudraCT Number)