NCT02871297

Long-term, Open-label, Flexible-dose, Extension Study of Vortioxetine in Child and Adolescent Participants With Major Depressive Disorder (MDD) From 7 to 18 Years of Age

Terminated Phase 3 Results posted Last updated 28 December 2022

What this trial tests

Phase 3 trial testing Vortioxetine in Depressive Disorder, Major in 662 participants. Terminated before completion.

Timeline

17 August 2016

Primary endpoint
25 March 2022

19 April 2022

Quick facts

Lead sponsor	H. Lundbeck A/S
Phase	Phase 3
Status	Terminated
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	662
Start date	17 August 2016
Primary completion	25 March 2022
Estimated completion	19 April 2022
Sites	78 locations across Italy, Colombia, Poland, South Korea, Russia, Estonia, Mexico, Bulgaria

Drugs / interventions tested

• Vortioxetine (vortioxetine) — full drug profile →

Conditions studied

• Depressive Disorder, Major — all drugs for Depressive Disorder, Major →

Sponsor

H. Lundbeck A/S — full company profile →

Who can join

Adults 7 to 18, any sex, with Depressive Disorder, Major. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Primary · Baseline up to Week 30

An adverse event (AE) was defined as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. SAEs included death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized the participant and required medical intervention to prevent 1 of the outcomes listed in this definition. TEAE was define

Group	Value	95% CI
Vortioxetine	404

Change From Baseline in Children Depression Rating Scale - Revised (CDRS-R) Total Score at Week 26 Secondary · Baseline, Week 26

CDRS-R consisted of 17 items out of which 3 items rated nonverbal observations (listless speech, hypoactivity, and depressed affect). Fourteen items were rated on a 7-point scale from 1 to 7, and 3 items (sleep disturbance, appetite disturbance, and listless speech) were scored on a 5-point scale from 1 to 5. A rating of 1 indicated normal functioning and a higher number indicated a greater degree of depression. Total score ranged from 17 (normal) to 113 (severe depression). Least square (LS) mean was calculated using a restricted maximum likelihood-based mixed model for repeated measurements

Group	Value	95% CI
Vortioxetine	-16.05	± 0.63

Change From Baseline in Clinical Global Impression - Severity of Illness (CGI-S) Score at Week 26 Secondary · Baseline, Week 26

The CGI-S provides the clinician's impression of the participant's current state of mental illness. The clinician uses his or her clinical experience of this participant population to rate the severity of the participant's current mental illness on a 7-point scale ranging from 1 (normal - not at all ill) to 7 (among the most extremely ill participants). LS mean was calculated using a restricted maximum likelihood-based MMRM approach.

Group	Value	95% CI
Vortioxetine	-1.48	± 0.06

Clinical Global Impression - Global Improvement (CGI-I) Score Secondary · Week 26

The CGI-I provides the clinician's impression of the participant's improvement (or worsening). The clinician assesses the participant's condition relative to a baseline on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). LS mean was calculated using a restricted maximum likelihood-based MMRM approach.

Group	Value	95% CI
Vortioxetine	1.72	± 0.04

Children (7-11 Years): Change From Baseline in Behaviour Rating Inventory of Executive Function - Preschool (BRIEF-P) Using the Global Executive Composite (GEC) Score at Week 26 Secondary · Baseline, Week 26

BRIEF form is an 86-item measure with symptoms rated on a 3-point likert scale of 1 "never", 2 "sometimes" or 3 "often". These items cover 8 non-overlapping clinical scales. For BRIEF-P form, only the first 72 items (Inhibit \[10\], Shift \[8\], Emotional Control \[10\], Initiate \[8\], Working Memory \[10\], Plan/Organize \[12\], Organization of Materials \[6\], Monitor \[8\]) were included in clinical scales. Clinical scales combined to form 2 indexes, Behavioural Regulation Index (BRI) and Metacognition Index (MI), and 1 composite summary score, the GEC, that incorporates all 8 clinical sca

Group	Value	95% CI
Vortioxetine	-7.41	± 11.70

Adolescents (12-18 Years): Change From Baseline in Behaviour Rating Inventory of Executive Function - Self-report (BRIEF-SR) Using the GEC Score at Week 26 Secondary · Baseline, Week 26

BRIEF form is an 86-item measure that assesses impairment in executive function with symptoms rated on a 3-point likert scale of 1 "never", 2 "sometimes" or 3 "often". These items cover 8 non-overlapping clinical scales. For BRIEF-SR form, only 80 items (Inhibit \[13\], Shift \[10\], Emotional Control \[10\], Initiate \[5\], Working Memory \[12\], Plan/Organize \[13\], Organization of Materials \[7\], Monitor \[10\]) were included in clinical scales. Clinical scales combined to form 2 indexes, the BRI and the MI, and 1 composite summary score, the GEC, that incorporates all 8 clinical scales.

Group	Value	95% CI
Vortioxetine	-7.50	± 13.82

Children (7-11 Years): Change From Baseline in BRIEF-P Using the MI Score at Week 26 Secondary · Baseline, Week 26

BRIEF form is an 86-item measure that assesses impairment in executive function with symptoms rated on a 3-point likert scale of 1 "never", 2 "sometimes" or 3 "often". These items cover 8 non-overlapping clinical scales. Clinical scales combined to form 2 indexes, the BRI and the MI. For BRIEF-P, MI is comprised of Initiate (8), Working Memory (10), Plan/Organize (12), Organization of Materials (6), and Monitor (8) scales. The MI scores are calculated as the sum of the total 44 items ranging from 44 to 132 with lower scores reflecting better functioning. Raw scores converted to T-scores as det

Group	Value	95% CI
Vortioxetine	-7.36	± 11.98

Adolescents (12-18 Years): Change From Baseline in BRIEF-SR Using the MI Score at Week 26 Secondary · Baseline, Week 26

BRIEF form is an 86-item measure that assesses impairment in executive function with symptoms rated on a 3-point likert scale of 1 "never", 2 "sometimes" or 3 "often". These items cover 8 non-overlapping clinical scales. Clinical scales combined to form 2 indexes, the BRI and the MI. For BRIEF-SR, MI is comprised of Working Memory (12), Plan/Organize (13), Organization of Materials (7), and Task Completion (10) scales. The MI scores are calculated as the sum of the total 42 items ranging from 42 to 126 with lower scores reflecting better functioning. Raw scores converted to T-scores as detaile

Group	Value	95% CI
Vortioxetine	-7.18	± 13.71

Change From Baseline in Children's Global Assessment Scale (CGAS) Score at Week 26 Secondary · Baseline, Week 26

The CGAS is a clinician-rated global scale to measure the lowest level of functioning for a child (4 to 16 years) during a specified time period. The CGAS contains behaviourally-oriented descriptors at each anchor point that depict behaviours and life situations applicable to a child. The score ranges from 1 (most functionally impaired child) to 100 (the healthiest). A score greater than 70 indicates normal function.

Group	Value	95% CI
Vortioxetine	14.78	± 14.29

Change From Baseline in Pediatric Quality of Life Inventory Present Functioning Visual Analogue Scale (PedsQL VAS) Total Score at Week 26 Secondary · Baseline, Week 26

The PedsQL™ VAS is designed to measure at-that-moment functioning in children and adolescents. The PedsQL™ VAS consists of 6 domains: anxiety, sadness, anger, worry, fatigue, and pain using VAS. The functionality for each domain is measured on a 10 cm line with a happy face at one end and a sad face at the other (0-10 points). The participants are asked to mark on the line how they feel. The total score is the average of all 6 items ranging from 0 to 10, where a lower value represents a better outcome.

Group	Value	95% CI
Vortioxetine	-1.50	± 1.87

Number of Participants With Response to the Palatability Questionnaire Secondary · assessed at Baseline up to Week 26, Week 26 reported

The palatability of vortioxetine oral drops was assessed after intake of a single dose (5 to 20 mg) corresponding to the participant's current vortioxetine dose (replacing the vortioxetine tablet on that day). The palatability assessment included 4 questions on the overall appreciation of a medicinal product in relation to its taste (What do you think of the taste), mouthfeel (How does medicine feel in your mouth), aftertaste (What do you think of the after taste), and smell (What do you think of the smell). The items were rated on a 5-point hedonic scale; really bad, bad, neither good or bad,

Mouthfeel

Group	Value	95% CI
Vortioxetine	11
Vortioxetine	17
Vortioxetine	38
Vortioxetine	55

Aftertaste

Group	Value	95% CI
Vortioxetine	13
Vortioxetine	26
Vortioxetine	54
Vortioxetine	32

Smell

Group	Value	95% CI
Vortioxetine	4
Vortioxetine	4
Vortioxetine	37
Vortioxetine	59

Taste

Group	Value	95% CI
Vortioxetine	13
Vortioxetine	15
Vortioxetine	33
Vortioxetine	60

Number of Participants With Response to the Acceptability Questionnaire Secondary · assessed at Baseline up to Week 26, Week 26 reported

The acceptability of vortioxetine oral drops was assessed after intake of a single dose (5 to 20 mg) corresponding to the participant's current vortioxetine dose (replacing the vortioxetine tablet on that day). The acceptability assessment was based on 3 items; acceptability of the taste, whether the drops were perceived as easy to take, willingness to take the drops every day (provided it was the only available formulation). For each item the response options were no, not sure, and yes. The oral drops were considered acceptable if \<60% of participants responded "no" to each of the 3 question

Willingness to take the drops every day: No

Group	Value	95% CI
Vortioxetine	27

Willingness to take the drops every day: Not sure

Group	Value	95% CI
Vortioxetine	17

Willingness to take the drops every day: Yes

Group	Value	95% CI
Vortioxetine	109

Easy to take medicine: No

Group	Value	95% CI
Vortioxetine	8

Easy to take medicine: Neither easy or difficult

Group	Value	95% CI
Vortioxetine	10

Easy to take medicine: Yes

Group	Value	95% CI
Vortioxetine	135

Acceptability of the taste: No

Group	Value	95% CI
Vortioxetine	31

Acceptability of the taste: Not sure

Group	Value	95% CI
Vortioxetine	24

Adverse events — posted to ClinicalTrials.gov

Time frame: Baseline up to Week 30. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Vortioxetine

Serious: 14/662 (2%)

Deaths: 0/662

Serious adverse events (11 terms)

Reaction	System	Vortioxetine
Suicidal ideation	Psychiatric disorders	—
Suicide attempt	Psychiatric disorders	—
Intentional overdose	Injury, poisoning and procedural complications	—
Arthropathy	Musculoskeletal and connective tissue disorders	—
Osteitis	Musculoskeletal and connective tissue disorders	—
Torticollis	Musculoskeletal and connective tissue disorders	—
Psychomotor hyperactivity	Nervous system disorders	—
Major depression	Psychiatric disorders	—
Mania	Psychiatric disorders	—
Psychogenic seizure	Psychiatric disorders	—
Suicidal behaviour	Psychiatric disorders	—

Other adverse events (6 terms — click to expand)

Reaction	System	Vortioxetine
Nausea	Gastrointestinal disorders	—
Headache	Nervous system disorders	—
Vomiting	Gastrointestinal disorders	—
Abdominal pain	Gastrointestinal disorders	—
Nasopharyngitis	Infections and infestations	—
Dizziness	Nervous system disorders	—

Most-reported serious reactions: Suicidal ideation, Suicide attempt, Intentional overdose, Arthropathy, Osteitis, Torticollis, Psychomotor hyperactivity, Major depression.

Data from ClinicalTrials.gov NCT02871297 adverse events section.

Sponsor's own description

Evaluation of the long-term safety and tolerability of vortioxetine in child and adolescent participants with a Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5™) diagnosis of MDD.

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

1. New generation antidepressants for depression in children and adolescents: a network meta-analysis.
   Hetrick SE, McKenzie JE, Bailey AP, Sharma V, et al · · 2021 · cited 89× · PMID 34029378 · DOI 10.1002/14651858.cd013674.pub2
2. Vortioxetine in children and adolescents with major depressive disorder: 6-month and 18-month open-label, flexible-dose, long-term extension studies.
   DelBello MP, Findling RL, Huss M, Necking O, et al · · 2025 · cited 1× · PMID 39240359 · DOI 10.1007/s00787-024-02560-1