Clinical trial NCT01491035: Pharmacokinetics and Tolerability of Vortioxetine (Lu AA21004) in Child and Adolescent Patients With Depressive or Anxiety Disorder
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Depressive Disorder
Anxiety Disorder
Keywords: Children
Adolescents
Pharmacokinetic
Pharmacodynamic
Lead sponsor: H. Lundbeck A/S
Sponsor class: INDUSTRY
First posted: 2011-12-13
Enrollment: 48
Sex: ALL
Minimum age (years): 7
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Cmax of Vortioxetine
timeFrame: 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
measure: AUC(0-24h) of Vortioxetine
timeFrame: 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
measure: t½ of Vortioxetine
timeFrame: 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
measure: Cmax of Lu AA34443
timeFrame: 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
measure: AUC(0-24h) of Lu AA34443
timeFrame: 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
measure: t½ of Lu AA34443
timeFrame: 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
measure: Oral Clearance (CL/F) of Vortioxetine
timeFrame: 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
Secondary outcomes:
Other outcomes:
Locations:
city: Washington
country: United States
facility: US003
state: District of Columbia
city: Wichita
country: United States
facility: US004
state: Kansas
city: Cincinnatti
country: United States
facility: US002
state: Ohio
city: Cleveland
country: United States
facility: US001
state: Ohio
city: Berlin
country: Germany
facility: DE002
city: Mainz
country: Germany
facility: DE001
city: Ulm
country: Germany
facility: DE003
Study officials:
affiliation: LundbeckClinicalTrials@lundbeck.com
name: Email contact via H. Lundbeck A/S
role: STUDY_DIRECTOR
References:
citation: 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.