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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

Status
Completed
Phases
Phase 2
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT01491035
Enrollment
48
Registered
2011-12-13
Start date
2012-04-30
Completion date
2015-06-30
Last updated
2017-03-16

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Anxiety Disorder, Depressive Disorder

Keywords

Children, Adolescents, Pharmacokinetic, Pharmacodynamic

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.

Interventions

DRUGVortioxetine

5 mg tablets for 14 days; orally; once daily

Sponsors

H. Lundbeck A/S
Lead SponsorINDUSTRY

Study design

Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
7 Years to 17 Years
Healthy volunteers
No

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

Design outcomes

Primary

MeasureTime frameDescription
Cmax of VortioxetinePre-dose and 1, 3, 5, 8, 12 and 24 hours post-dose on Day 14, 16, 18, or 20, depending on assigned dose levelMaximum plasma concentration of vortioxetine
AUC(0-24h) of VortioxetinePre-dose and 1, 3, 5, 8, 12 and 24 hours post-dose on Day 14, 16, 18 or 20, depending on assigned dose levelArea under the vortioxetine plasma concentration-time curve from 0 to 24 hours
t½ of VortioxetinePre-dose and 1, 3, 5, 8, 12 and 24 hours post-dose on Day 14, 16, 18 or 20, depending on assigned dose levelHalf-life of vortioxetine in plasma
Cmax of Lu AA34443Pre-dose and 1, 3, 5, 8, 12 and 24 hours post-dose on Day 14, 16, 18, or 20, depending on assigned dose levelMaximum plasma concentration of the major, inactive metabolite Lu AA34443
AUC(0-24h) of Lu AA34443Pre-dose and 1, 3, 5, 8, 12 and 24 hours post-dose on Day 14, 16, 18 or 20, depending on assigned dose levelArea under the plasma concentration-time curve from 0 to 24 hours for the major, inactive metabolite Lu AA34443
t½ of Lu AA34443Pre-dose and 1, 3, 5, 8, 12 and 24 hours post-dose on Day 14, 16, 18 or 20, depending on assigned dose levelHalf-life of the major, inactive metabolite Lu AA34443 in plasma
Oral Clearance (CL/F) of VortioxetinePre-dose and 1, 3, 5, 8, 12 and 24 hours post-dose on Day 14, 16, 18 or 20, depending on assigned dose levelOral clearance expressed as a function of bioavailability

Countries

Germany, United States

Participant flow

Participants by arm

ArmCount
Adolescents, 5 mg
Vortioxetine: 5 mg tablets for 14 days; orally; once daily
6
Adolescents, 10 mg
Vortioxetine: 10 mg tablets for 14 days (initial up-titration with 5 mg/day for 2 days); orally; once daily
6
Adolescents, 15 mg
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
6
Adolescents, 20 mg
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
6
Children, 5 mg
Vortioxetine: 5 mg tablets for 14 days; orally; once daily
6
Children, 10 mg
Vortioxetine: 10 mg tablets for 14 days (initial up-titration with 5 mg/day for 2 days); orally; once daily
6
Children, 15 mg
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
6
Children, 20 mg
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
6
Total48

Withdrawals & dropouts

PeriodReasonFG000FG001FG002FG003FG004FG005FG006FG007
Overall StudyLost to Follow-up00001000

Baseline characteristics

CharacteristicAdolescents, 5 mgAdolescents, 10 mgAdolescents, 15 mgAdolescents, 20 mgChildren, 5 mgChildren, 10 mgChildren, 15 mgChildren, 20 mgTotal
Age, Continuous15.7 years
STANDARD_DEVIATION 1.9
15.3 years
STANDARD_DEVIATION 1.9
15.2 years
STANDARD_DEVIATION 1.2
14.8 years
STANDARD_DEVIATION 1.9
10.3 years
STANDARD_DEVIATION 1.2
9.7 years
STANDARD_DEVIATION 1.2
10.5 years
STANDARD_DEVIATION 0.8
9.8 years
STANDARD_DEVIATION 1.8
12.7 years
STANDARD_DEVIATION 3
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
Asian
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
Black or African American
1 Participants2 Participants1 Participants2 Participants1 Participants4 Participants3 Participants2 Participants16 Participants
Race (NIH/OMB)
More than one race
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants
Race (NIH/OMB)
Unknown or Not Reported
1 Participants0 Participants1 Participants0 Participants1 Participants0 Participants0 Participants0 Participants3 Participants
Race (NIH/OMB)
White
4 Participants4 Participants4 Participants4 Participants4 Participants2 Participants3 Participants4 Participants29 Participants
Region of Enrollment
Germany
0 participants0 participants0 participants3 participants2 participants0 participants0 participants0 participants5 participants
Region of Enrollment
United States
6 participants6 participants6 participants3 participants4 participants6 participants6 participants6 participants43 participants
Sex: Female, Male
Female
3 Participants3 Participants5 Participants4 Participants3 Participants3 Participants2 Participants2 Participants25 Participants
Sex: Female, Male
Male
3 Participants3 Participants1 Participants2 Participants3 Participants3 Participants4 Participants4 Participants23 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
EG002
affected / at risk
EG003
affected / at risk
EG004
affected / at risk
EG005
affected / at risk
EG006
affected / at risk
EG007
affected / at risk
deaths
Total, all-cause mortality
— / —— / —— / —— / —— / —— / —— / —— / —
other
Total, other adverse events
4 / 64 / 65 / 65 / 65 / 65 / 65 / 64 / 6
serious
Total, serious adverse events
0 / 60 / 60 / 60 / 60 / 60 / 60 / 60 / 6

Outcome results

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

Time frame: 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

Population: Pharmacokinetic analysis set

ArmMeasureValue (MEDIAN)Dispersion
Adolescents, 5 mgAUC(0-24h) of Lu AA3444356 ng*h/mLStandard Deviation 29
Adolescents, 10 mgAUC(0-24h) of Lu AA34443223 ng*h/mLStandard Deviation 98
Adolescents, 15 mgAUC(0-24h) of Lu AA34443266 ng*h/mLStandard Deviation 100
Adolescents, 20 mgAUC(0-24h) of Lu AA34443544 ng*h/mLStandard Deviation 192
Children, 5 mgAUC(0-24h) of Lu AA34443115 ng*h/mLStandard Deviation 47
Children, 10 mgAUC(0-24h) of Lu AA34443241 ng*h/mLStandard Deviation 93
Children, 15 mgAUC(0-24h) of Lu AA34443429 ng*h/mLStandard Deviation 232
Children, 20 mgAUC(0-24h) of Lu AA34443646 ng*h/mLStandard Deviation 251
Primary

AUC(0-24h) of Vortioxetine

Area under the vortioxetine plasma concentration-time curve from 0 to 24 hours

Time frame: 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

Population: Pharmacokinetic analysis set

ArmMeasureValue (MEDIAN)Dispersion
Adolescents, 5 mgAUC(0-24h) of Vortioxetine82 ng*h/mLStandard Deviation 71
Adolescents, 10 mgAUC(0-24h) of Vortioxetine144 ng*h/mLStandard Deviation 60
Adolescents, 15 mgAUC(0-24h) of Vortioxetine283 ng*h/mLStandard Deviation 115
Adolescents, 20 mgAUC(0-24h) of Vortioxetine304 ng*h/mLStandard Deviation 143
Children, 5 mgAUC(0-24h) of Vortioxetine89 ng*h/mLStandard Deviation 66
Children, 10 mgAUC(0-24h) of Vortioxetine261 ng*h/mLStandard Deviation 137
Children, 15 mgAUC(0-24h) of Vortioxetine492 ng*h/mLStandard Deviation 373
Children, 20 mgAUC(0-24h) of Vortioxetine562 ng*h/mLStandard Deviation 374
Primary

Cmax of Lu AA34443

Maximum plasma concentration of the major, inactive metabolite Lu AA34443

Time frame: 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

Population: Pharmacokinetic analysis set

ArmMeasureValue (MEDIAN)Dispersion
Adolescents, 5 mgCmax of Lu AA344433.5 ng/mLStandard Deviation 2.2
Adolescents, 10 mgCmax of Lu AA3444314 ng/mLStandard Deviation 7.1
Adolescents, 15 mgCmax of Lu AA3444316 ng/mLStandard Deviation 5.3
Adolescents, 20 mgCmax of Lu AA3444338 ng/mLStandard Deviation 12
Children, 5 mgCmax of Lu AA344437.8 ng/mLStandard Deviation 3.4
Children, 10 mgCmax of Lu AA3444315 ng/mLStandard Deviation 5.4
Children, 15 mgCmax of Lu AA3444320 ng/mLStandard Deviation 13
Children, 20 mgCmax of Lu AA3444347 ng/mLStandard Deviation 17
Primary

Cmax of Vortioxetine

Maximum plasma concentration of vortioxetine

Time frame: 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

Population: Pharmacokinetic analysis set = all patients who took at least one dose of IMP and who contributed with both Day 1 pre-dose pharmacokinetic sampling data and sufficient post-dose sampling data for estimation of the pharmacokinetic parameters.

ArmMeasureValue (MEDIAN)Dispersion
Adolescents, 5 mgCmax of Vortioxetine4.3 ng/mLStandard Deviation 3.7
Adolescents, 10 mgCmax of Vortioxetine7.8 ng/mLStandard Deviation 2.8
Adolescents, 15 mgCmax of Vortioxetine15 ng/mLStandard Deviation 6.2
Adolescents, 20 mgCmax of Vortioxetine16 ng/mLStandard Deviation 8.1
Children, 5 mgCmax of Vortioxetine5.0 ng/mLStandard Deviation 3.3
Children, 10 mgCmax of Vortioxetine14 ng/mLStandard Deviation 8.2
Children, 15 mgCmax of Vortioxetine26 ng/mLStandard Deviation 21
Children, 20 mgCmax of Vortioxetine31 ng/mLStandard Deviation 20
Primary

Oral Clearance (CL/F) of Vortioxetine

Oral clearance expressed as a function of bioavailability

Time frame: 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

Population: Pharmacokinetic analysis set

ArmMeasureValue (MEDIAN)Dispersion
Adolescents, 5 mgOral Clearance (CL/F) of Vortioxetine60 L/hStandard Deviation 55
Adolescents, 10 mgOral Clearance (CL/F) of Vortioxetine50 L/hStandard Deviation 16
Adolescents, 15 mgOral Clearance (CL/F) of Vortioxetine50 L/hStandard Deviation 23
Adolescents, 20 mgOral Clearance (CL/F) of Vortioxetine61 L/hStandard Deviation 20
Children, 5 mgOral Clearance (CL/F) of Vortioxetine50 L/hStandard Deviation 16
Children, 10 mgOral Clearance (CL/F) of Vortioxetine42 L/hStandard Deviation 25
Children, 15 mgOral Clearance (CL/F) of Vortioxetine29 L/hStandard Deviation 33
Children, 20 mgOral Clearance (CL/F) of Vortioxetine34 L/hStandard Deviation 17
Primary

t½ of Lu AA34443

Half-life of the major, inactive metabolite Lu AA34443 in plasma

Time frame: 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

Population: Pharmacokinetic analysis set

ArmMeasureValue (MEDIAN)Dispersion
Adolescents, 5 mgt½ of Lu AA3444326 hStandard Deviation 9.3
Adolescents, 10 mgt½ of Lu AA3444333 hStandard Deviation 13
Adolescents, 15 mgt½ of Lu AA3444324 hStandard Deviation 11
Adolescents, 20 mgt½ of Lu AA3444324 hStandard Deviation 5.1
Children, 5 mgt½ of Lu AA3444320 hStandard Deviation 24
Children, 10 mgt½ of Lu AA3444319 hStandard Deviation 9.6
Children, 15 mgt½ of Lu AA3444329 hStandard Deviation 6.1
Children, 20 mgt½ of Lu AA3444327 hStandard Deviation 8.8
Primary

t½ of Vortioxetine

Half-life of vortioxetine in plasma

Time frame: 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

Population: Pharmacokinetic analysis set

ArmMeasureValue (MEDIAN)Dispersion
Adolescents, 5 mgt½ of Vortioxetine46 hStandard Deviation 33
Adolescents, 10 mgt½ of Vortioxetine56 hStandard Deviation 19
Adolescents, 15 mgt½ of Vortioxetine50 hStandard Deviation 16
Adolescents, 20 mgt½ of Vortioxetine40 hStandard Deviation 10
Children, 5 mgt½ of Vortioxetine45 hStandard Deviation 27
Children, 10 mgt½ of Vortioxetine52 hStandard Deviation 18
Children, 15 mgt½ of Vortioxetine71 hStandard Deviation 52
Children, 20 mgt½ of Vortioxetine62 hStandard Deviation 23

Source: ClinicalTrials.gov · Data processed: Mar 8, 2026