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Clinical Trial Results:
Interventional, randomised, double-blind, placebo-controlled, active reference (fluoxetine), fixed-dose study of vortioxetine in paediatric patients aged 12 to 17 years, with Major depressive disorder (MDD)

Summary
EudraCT number	2008-005354-20
Trial protocol	LV EE GB HU BG DE FI IT ES BE PL FR
Global end of trial date	30 Jul 2019

Results information
Results version number	v1(current)
This version publication date	18 Jan 2020
First version publication date	18 Jan 2020
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

12710A

ISRCTN number

US NCT number

NCT02709746

WHO universal trial number (UTN)

Sponsor organisation name

H. Lundbeck A/S

Sponsor organisation address

Ottiliavej 9, Valby, Denmark, 2500

Public contact

LundbeckClinicalTrials@Lundbeck.com, H. Lundbeck A/S, +45 36 3013 11, LundbeckClinicalTrials@lundbeck.com

Scientific contact

LundbeckClinicalTrials@Lundbeck.com, H. Lundbeck A/S, +45 36 3013 11, LundbeckClinicalTrials@lundbeck.com

Is trial part of an agreed paediatric investigation plan (PIP)

Yes

EMA paediatric investigation plan number(s)

EMEA-000455-PIP02-10

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

30 Jul 2019

Is this the analysis of the primary completion data?

Yes

Primary completion date

02 Jul 2019

Global end of trial reached?

Yes

Global end of trial date

30 Jul 2019

Was the trial ended prematurely?

Main objective of the trial

Evaluation of the efficacy of vortioxetine 10 mg/day and 20 mg/day versus placebo on depressive symptoms in adolescents with a DSM-5™ diagnosis of MDD.

Protection of trial subjects

The trial was conducted in accordance with the Declaration of Helsinki (2013) and ICH Good Clinical Practice (1996).

Background therapy

Evidence for comparator

Actual start date of recruitment

10 Feb 2016

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

United States: 311

Country: Number of subjects enrolled

Russian Federation: 100

Country: Number of subjects enrolled

Mexico: 57

Country: Number of subjects enrolled

Colombia: 32

Country: Number of subjects enrolled

Serbia: 27

Country: Number of subjects enrolled

Ukraine: 11

Country: Number of subjects enrolled

Korea, Republic of: 7

Country: Number of subjects enrolled

South Africa: 7

Country: Number of subjects enrolled

Canada: 4

Country: Number of subjects enrolled

Poland: 69

Country: Number of subjects enrolled

Spain: 20

Country: Number of subjects enrolled

United Kingdom: 6

Country: Number of subjects enrolled

Bulgaria: 23

Country: Number of subjects enrolled

Estonia: 19

Country: Number of subjects enrolled

France: 14

Country: Number of subjects enrolled

Germany: 22

Country: Number of subjects enrolled

Hungary: 7

Country: Number of subjects enrolled

Italy: 19

Country: Number of subjects enrolled

Latvia: 29

Worldwide total number of subjects

784

EEA total number of subjects

228

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

784

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Screening details

Subjects who met each of the inclusion and none of the exclusion criteria were eligible to participate in the study.

Period 1 title

Phase A (Single-blind treatment period)

Is this the baseline period?

Allocation method

Non-randomised - controlled

Blinding used

Single blind

Roles blinded

Subject

Single-blind Treatment (SBT), Placebo

Arm description

Single-blind Treatment, Placebo and Brief Psychosocial Intervention (BPI) for 4 weeks

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Encapsulated, orally

Number of subjects in period 1	Single-blind Treatment (SBT), Placebo
Started	784
Completed	616
Not completed	168
non-compliance with IMP	12
Consent withdrawn by subject	12
Adverse event, non-fatal	2
Other	14
Did not fulfil rand criteria for DB period	103
Lost to follow-up	7
Enrolled but not treated	7
Lack of efficacy	7
Protocol deviation	4

Period 2 title

Phase B (Double-blind treatment period)

Is this the baseline period?

Yes ^[1]

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator

Are arms mutually exclusive

Yes

DBT, Vortioxetine 10 mg

Arm description

Eligible patients from Phase A (patients with incomplete improvement), will be randomly assigned (1:1:1:1) double-blind treatment in DBT Period, 8 weeks. Vortioxetine 10 mg/day, encapsulated tablets, orally.

Arm type

Experimental

Investigational medicinal product name

Vortioxetine 10 mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Vortioxetine 10 mg/day, encapsulated, orally

DBT, Vortioxetine 20 mg

Arm description

Eligible patients from Phase A (patients with incomplete improvement), will be randomly assigned (1:1:1:1) double-blind treatment in DBT Period, 8 weeks. Vortioxetine 20 mg/day, encapsulated tablets, orally.

Arm type

Experimental

Investigational medicinal product name

Vortioxetine 20 mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Vortioxetine 20 mg/day, encapsulated, orally

DBT, Fluoxetine 20 mg

Arm description

Eligible patients from Phase A (patients with incomplete improvement), will be randomly assigned (1:1:1:1) double-blind treatment in DBT Period, 8 weeks. Fluoxetine 20 mg/day, encapsulated tablets, orally.

Arm type

Experimental

Investigational medicinal product name

Fluoxetine 20 mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Fluoxetine 20 mg/day, encapsulated, orally

DBT, Placebo

Arm description

Eligible patients from Phase A (patients with incomplete improvement), will be randomly assigned (1:1:1:1) double-blind treatment in DBT Period, 8 weeks. Placebo, encapsulated tablets, orally.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Placebo, encapsulated, orally

Notes
[1] - Period 1 is not the baseline period. It is expected that period 1 will be the baseline period.
Justification: Patients are randomized at the start of Period 2, therefor Period 2 can be seen as a baseline period, whereas Period 1 is a lead-in period.

Number of subjects in period 2 ^[2]	DBT, Vortioxetine 10 mg	DBT, Vortioxetine 20 mg	DBT, Fluoxetine 20 mg	DBT, Placebo
Started	147	162	153	154
Completed	126	140	138	138
Not completed	21	22	15	16
non-compliance with IMP	1	4	1	-
Consent withdrawn by subject	2	2	2	1
Enrolled not treated	-	1	-	-
Adverse event, non-fatal	4	8	5	2
Other	6	5	6	7
Lost to follow-up	4	2	-	2
Lack of efficacy	3	-	1	2
Protocol deviation	1	-	-	2

Notes
[2] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
Justification: Patients are randomized at the start of Period 2, therefor Period 2 can be seen as a baseline period, whereas Period 1 is a lead-in period.

Baseline characteristics

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Reporting group title

DBT, Vortioxetine 10 mg

Reporting group description

Reporting group title

DBT, Vortioxetine 20 mg

Reporting group description

Reporting group title

DBT, Fluoxetine 20 mg

Reporting group description

Reporting group title

DBT, Placebo

Reporting group description

Eligible patients from Phase A (patients with incomplete improvement), will be randomly assigned (1:1:1:1) double-blind treatment in DBT Period, 8 weeks. Placebo, encapsulated tablets, orally.

Reporting group values	DBT, Vortioxetine 10 mg	DBT, Vortioxetine 20 mg	DBT, Fluoxetine 20 mg	DBT, Placebo	Total
Number of subjects	147	162	153	154	616
Age categorical
Units: Subjects
Adolescents (12-17 years)	147	162	153	154	616
Age continuous
Units: years
arithmetic mean (standard deviation)	14.8 ( 1.66 )	14.5 ( 1.63 )	14.8 ( 1.6 )	14.6 ( 1.6 )	-
Gender categorical
Units: Subjects
Female	93	97	103	105	398
Male	54	65	50	49	218
CDSR-S total score at enrolment
Units: Units on a scale
arithmetic mean (standard deviation)	64.82 ( 9.38 )	65.29 ( 9.73 )	64.06 ( 8.65 )	64.02 ( 8.96 )	-
CGI-S at Enrolment
Units: Units on a scale
arithmetic mean (standard deviation)	4.99 ( 0.77 )	5.00 ( 0.71 )	4.97 ( 0.68 )	4.92 ( 0.69 )	-

End points

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Reporting group title

Single-blind Treatment (SBT), Placebo

Reporting group description

Single-blind Treatment, Placebo and Brief Psychosocial Intervention (BPI) for 4 weeks

Reporting group title

DBT, Vortioxetine 10 mg

Reporting group description

Reporting group title

DBT, Vortioxetine 20 mg

Reporting group description

Reporting group title

DBT, Fluoxetine 20 mg

Reporting group description

Reporting group title

DBT, Placebo

Reporting group description

Eligible patients from Phase A (patients with incomplete improvement), will be randomly assigned (1:1:1:1) double-blind treatment in DBT Period, 8 weeks. Placebo, encapsulated tablets, orally.

Subject analysis set title

Vortioxetine average (Avg. VOR)

Subject analysis set type

Full analysis

Subject analysis set description

The primary comparison was the average effect of the two vortioxetine (Avg. VOR) doses versus placebo at Week 8 in the DB Period. The testing strategy also included comparisons of the individual vortioxetine doses versus placebo. First, the comparison of the average effect of the two vortioxetine doses versus placebo was tested at a two-sided 5% significance level. If significance was achieved, each vortioxetine dose was tested separately versus placebo at a two-sided 5% significance level. Statistical significance could be claimed on the individual doses only if significance was claimed for the average vortioxetine doses.

Primary: Change in Children Depression Rating Scale - Revised (CDRS-R) total score after treatment

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End point title

Change in Children Depression Rating Scale - Revised (CDRS-R) total score after treatment

End point description

The CDRS-R is a clinician-rated scale to measure the severity of depression of children and adolescents. The CDRS-R consists of 17 items: 14 items rate verbal observations, and three items rate nonverbal observations (tempo of language, hypoactivity, and nonverbal expression of depressed affect). Depression symptoms are rated on a 5-point scale from 1 to 5 for the verbal observations, and a 7-point scale from 1 to 7 for the nonverbal observations. The total score ranges from 17 (normal) to 113 (severe depression). Children and parents answer separately. Rater judges and selects 'Best'.

End point type

Primary

End point timeframe

From randomization to Week 8

End point values	DBT, Vortioxetine 10 mg	DBT, Vortioxetine 20 mg	DBT, Fluoxetine 20 mg	DBT, Placebo	Vortioxetine average (Avg. VOR)
Number of subjects analysed	126	139	137	137	265 ^[1]
Units: units on a scale
least squares mean (standard error)	-17.09 ( 1.27 )	-18.94 ( 1.22 )	-21.95 ( 1.23 )	-18.22 ( 1.22 )	-18.01 ( 0.98 )

Notes
[1] - 126 patients for 10 mg vortioxetine and 139 patients for 20 mg vortioxetine

Vortioxetine 10 mg vs placebo

Statistical analysis description

Only patients randomized to receive double-blind treatment in the DBT Period are analyzed. Overall Number of Participants analyzed is number of patients in the FAS with a week 8 observation.

Comparison groups

DBT, Placebo v DBT, Vortioxetine 10 mg

Number of subjects included in analysis

263

Analysis specification

Pre-specified

Analysis type

superiority ^[2]

P-value

= 0.4702

Method

Mixed Model Repeated Measures

Parameter type

Mean difference (final values)

Point estimate

1.13

Confidence interval

level

95%

sides

2-sided

lower limit

-1.94

upper limit

4.2

Notes
[2] - The change from Randomization in CDRS-R total score at Week 8 was analysed using a restricted maximum likelihood (REML) based mixed model for repeated measures (MMRM). The model included the fixed, categorical effects of treatment, country, and week, the continuous covariate of CDRS-R total score at Randomization, the treatment-by-week interaction, and the CDRS-R at Randomization-by-week interaction. The Kenward-Roger approximation was used to estimate denominator degrees of freedom.

Vortioxetine 20 mg vs placebo

Statistical analysis description

Only patients randomized to receive double-blind treatment in the DBT Period are analyzed. Overall Number of Participants analyzed is number of patients in the FAS with a week 8 observation.

Comparison groups

DBT, Vortioxetine 20 mg v DBT, Placebo

Number of subjects included in analysis

276

Analysis specification

Pre-specified

Analysis type

superiority ^[3]

P-value

= 0.6373

Method

Mixed Model Repeated Measures

Parameter type

Mean difference (final values)

Point estimate

-0.72

Confidence interval

level

95%

sides

2-sided

lower limit

-3.71

upper limit

2.27

Notes
[3] - The change from Randomization in CDRS-R total score at Week 8 was analysed using a restricted maximum likelihood (REML) based mixed model for repeated measures (MMRM). The model included the fixed, categorical effects of treatment, country, and week, the continuous covariate of CDRS-R total score at Randomization, the treatment-by-week interaction, and the CDRS-R at Randomization-by-week interaction. The Kenward-Roger approximation was used to estimate denominator degrees of freedom.

Fluoxetine 20 mg vs placebo

Statistical analysis description

Only patients randomized to receive double-blind treatment in the DBT Period are analyzed. Overall Number of Participants analyzed is number of patients in the FAS with a week 8 observation.

Comparison groups

DBT, Fluoxetine 20 mg v DBT, Placebo

Number of subjects included in analysis

274

Analysis specification

Pre-specified

Analysis type

superiority ^[4]

P-value

= 0.0152

Method

Mixed Model Repeated Measures

Parameter type

Mean difference (final values)

Point estimate

-3.73

Confidence interval

level

95%

sides

2-sided

lower limit

-6.74

upper limit

-0.72

Notes
[4] - The change from Randomization in CDRS-R total score at Week 8 was analysed using a restricted maximum likelihood (REML) based mixed model for repeated measures (MMRM). The model included the fixed, categorical effects of treatment, country, and week, the continuous covariate of CDRS-R total score at Randomization, the treatment-by-week interaction, and the CDRS-R at Randomization-by-week interaction. The Kenward-Roger approximation was used to estimate denominator degrees of freedom.

Vortioxetine average vs placebo

Statistical analysis description

The primary comparison was the average effect of the two vortioxetine (Avg. VOR) doses versus placebo at Week 8 in the DB Period based on the SAS lsmestimate statement. The testing strategy also included comparisons of the individual vortioxetine doses versus placebo. First, the comparison of the average effect of the two vortioxetine doses versus placebo was tested at a two-sided 5% significance level. If significance was achieved, each vortioxetine dose was tested separately versus placebo

Comparison groups

DBT, Placebo v Vortioxetine average (Avg. VOR)

Number of subjects included in analysis

402

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.8778

Method

Mixed Model Repeated Measures

Parameter type

Mean difference (final values)

Point estimate

0.21

Confidence interval

level

95%

sides

2-sided

lower limit

-2.41

upper limit

2.82

Secondary: Change in CDRS-R total score during treatment (at Week 2)

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End point title

Change in CDRS-R total score during treatment (at Week 2)

End point description

End point type

Secondary

End point timeframe

At week 2

End point values	DBT, Vortioxetine 10 mg	DBT, Vortioxetine 20 mg	DBT, Fluoxetine 20 mg	DBT, Placebo
Number of subjects analysed	145	158	150	153
Units: units on a scale
least squares mean (standard error)	-9.58 ( 1.02 )	-10.15 ( 0.99 )	-10.34 ( 1.00 )	-8.83 ( 0.98 )

No statistical analyses for this end point

Secondary: Change in CDRS-R MOOD Score

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End point title

Change in CDRS-R MOOD Score

End point description

Change in Children Depression Rating Scale - Revised (CDRS-R) Mood. The CDRS-R has been widely used for the evaluation of children and adolescents with major depressive disorder (MDD). The CDRS-R total score is the sum of the responses to 17 items. Each item is graded on a 5- or 7-point scale. Mood is one of four subscores defined in the CDRS-R: sum of items 8, 11, 14, 15; score range 4 to 28. The highest possible score indicates the most severe measure of depression.

End point type

Secondary

End point timeframe

From Randomization to Week 8

End point values	DBT, Vortioxetine 10 mg	DBT, Vortioxetine 20 mg	DBT, Fluoxetine 20 mg	DBT, Placebo
Number of subjects analysed	126	139	137	137
Units: units on a scale
least squares mean (standard error)	-5.05 ( 0.40 )	-5.47 ( 0.38 )	-6.53 ( 0.38 )	-5.32 ( 0.38 )

No statistical analyses for this end point

Secondary: CDRS-R response

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End point title

CDRS-R response

End point description

Children Depression Rating Scale - Response: defined as a >= 50% decrease in CDRS-R total score, calculated as (change from baseline [Randomization])/(baseline value - 17).

End point type

Secondary

End point timeframe

From Randomization to Week 8

End point values	DBT, Vortioxetine 10 mg	DBT, Vortioxetine 20 mg	DBT, Fluoxetine 20 mg	DBT, Placebo
Number of subjects analysed	126	139	137	137
Units: Number of patients	53	60	68	49

No statistical analyses for this end point

Secondary: CDRS-R remission

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End point title

CDRS-R remission

End point description

Remission defined as a CDRS-R total score<= 28.

End point type

Secondary

End point timeframe

From Randomization to Week 8

End point values	DBT, Vortioxetine 10 mg	DBT, Vortioxetine 20 mg	DBT, Fluoxetine 20 mg	DBT, Placebo
Number of subjects analysed	126	139	137	137
Units: Number of patients	21	24	32	20

No statistical analyses for this end point

Secondary: Change in General Behaviour Inventory (GBI) depression sub scale score assessed by the Parents

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End point title

Change in General Behaviour Inventory (GBI) depression sub scale score assessed by the Parents

End point description

Using the 10-item depression subscale, assessed by parent (PGBI-10D). Change from Baseline to Week 30 in GBI Total Parent/Guardian Version Depression score, using LOCF. GBI is a self-report inventory with 73 items focused on mood-related behaviors including depressive, hypomanic, and biphasic symptoms. One 20-item subscale completed by parent/guardian. Symptoms rated on 4-point Likert scale from 0 (never/hardly ever) to 3 (often/almost constantly). Minimum score 0=better outcome, maximum score 60=worse outcome

End point type

Secondary

End point timeframe

From Randomization to Week 8

End point values	DBT, Vortioxetine 10 mg	DBT, Vortioxetine 20 mg	DBT, Fluoxetine 20 mg	DBT, Placebo
Number of subjects analysed	126	139	137	137
Units: units on a scale
least squares mean (standard error)	-6.23 ( 0.56 )	-6.48 ( 0.54 )	-8.00 ( 0.54 )	-6.62 ( 0.53 )

No statistical analyses for this end point

Secondary: Parent Global Assessment–Global Improvement (PGA) score

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End point title

Parent Global Assessment–Global Improvement (PGA) score

End point description

The PGA is a parent-rated variation of the CGI-I to evaluate the severity of the child’s symptoms. The PGA reflects assessments of change from Baseline symptoms using a 7 point scale ranging from 1 (very much improved) to 7 (very much worse).

End point type

Secondary

End point timeframe

From Randomizationto Week 8

End point values	DBT, Vortioxetine 10 mg	DBT, Vortioxetine 20 mg	DBT, Fluoxetine 20 mg	DBT, Placebo
Number of subjects analysed	125	139	137	137
Units: Units on a scale
least squares mean (standard error)	2.80 ( 0.10 )	2.74 ( 0.09 )	2.49 ( 0.09 )	2.72 ( 0.09 )

No statistical analyses for this end point

Secondary: Change in Symbol Digit Modalities Test (SDMT)

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End point title

Change in Symbol Digit Modalities Test (SDMT)

End point description

The Symbol Digit Modalities Test (SDMT) is a cognitive test designed to assess speed of performance requiring visual perception, spatial decision-making and psychomotor skills. The SDMT consists of 110 geometric symbols that the patient has to substitute with a corresponding digit in a 90-second period. Each correct digit is counted, and the total score ranges from 0 (less than normal functioning) to 110 (greater than normal functioning).

End point type

Secondary

End point timeframe

From Randomizationto Week 8

End point values	DBT, Vortioxetine 10 mg	DBT, Vortioxetine 20 mg	DBT, Fluoxetine 20 mg	DBT, Placebo
Number of subjects analysed	125	140	138	137
Units: units on a scale
least squares mean (standard error)	3.75 ( 1.02 )	2.64 ( 0.98 )	2.69 ( 0.98 )	2.41 ( 0.97 )

No statistical analyses for this end point

Secondary: Change in Clinical Global Impression severity of illness (CGI-S) score

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End point title

Change in Clinical Global Impression severity of illness (CGI-S) score

End point description

The CGI-S provides the clinician's impression of the patient's current state of mental illness. The clinician uses his or her clinical experience of this patient population to rate the severity of the patient's current mental illness on a 7-point scale ranging from 1 (normal - not at all ill) to 7 (among the most extremely ill patients).

End point type

Secondary

End point timeframe

From Randomization to Week 8

End point values	DBT, Vortioxetine 10 mg	DBT, Vortioxetine 20 mg	DBT, Fluoxetine 20 mg	DBT, Placebo
Number of subjects analysed	126	139	137	137
Units: Units on a scale
least squares mean (standard error)	-1.23 ( 0.10 )	-1.38 ( 0.10 )	-1.59 ( 0.10 )	-1.21 ( 0.10 )

No statistical analyses for this end point

Secondary: Clinical Global Impression - global improvement (CGI-I) score

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End point title

Clinical Global Impression - global improvement (CGI-I) score

End point description

The CGI-I provides the clinician's impression of the patient's improvement (or worsening). The clinician assesses the patient's condition relative to a baseline on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). In all cases, the assessment should be made independent of whether the rater believes the improvement is drug-related or not.

End point type

Secondary

End point timeframe

At Week 8

End point values	DBT, Vortioxetine 10 mg	DBT, Vortioxetine 20 mg	DBT, Fluoxetine 20 mg	DBT, Placebo
Number of subjects analysed	125	139	137	137
Units: Units on a scale
least squares mean (standard error)	2.81 ( 0.10 )	2.69 ( 0.09 )	2.50 ( 0.09 )	2.73 ( 0.09 )

No statistical analyses for this end point

Secondary: Change in Children’s Global Assessment Scale (CGAS) score

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End point title

Change in Children’s Global Assessment Scale (CGAS) score

End point description

The Children's Global Assessment Score (CGAS) is a rating scale which measures psychological, social and school functioning for children. 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 items range in value from 1 (most functionally impaired child) to 100 (the healthiest). A total score above 70 indicates normal function.

End point type

Secondary

End point timeframe

From Randomization to Week 8

End point values	DBT, Vortioxetine 10 mg	DBT, Vortioxetine 20 mg	DBT, Fluoxetine 20 mg	DBT, Placebo
Number of subjects analysed	126	140	138	137
Units: Units on a scale
least squares mean (standard error)	12.24 ( 1.25 )	13.89 ( 1.20 )	16.43 ( 1.20 )	14.52 ( 1.19 )

No statistical analyses for this end point

Secondary: Change in Pediatric Quality of Life Inventory (PedsQL) Visual Analogue Scales (VAS): afraid or scared Score

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End point title

Change in Pediatric Quality of Life Inventory (PedsQL) Visual Analogue Scales (VAS): afraid or scared Score

End point description

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 visual analogue scales. 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. The patients are asked to mark on the line how they feel. The total score is the average of all 6 items, and the emotional distress summary score is the mean of the anxiety, sadness, anger, and worry items.

End point type

Secondary

End point timeframe

From Randomization to Week 8

End point values	DBT, Vortioxetine 10 mg	DBT, Vortioxetine 20 mg	DBT, Fluoxetine 20 mg	DBT, Placebo
Number of subjects analysed	124	140	138	137
Units: Units on a scale
least squares mean (standard error)	-0.47 ( 0.19 )	-0.76 ( 0.18 )	-0.78 ( 0.18 )	-0.71 ( 0.18 )

No statistical analyses for this end point

Secondary: Change in PedsQL VAS total average score

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End point title

Change in PedsQL VAS total average score

End point description

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 visual analogue scales. The functionality for each domain is measured on a 10cm line with a happy face at one end and a sad face at the other. The patients are asked to mark on the line how they feel. The total score is the average of all 6 items, and the emotional distress summary score is the mean of the anxiety, sadness, anger, and worry items.

End point type

Secondary

End point timeframe

From Randomization to Week 8

End point values	DBT, Vortioxetine 10 mg	DBT, Vortioxetine 20 mg	DBT, Fluoxetine 20 mg	DBT, Placebo
Number of subjects analysed	124	140	138	137
Units: Units on a scale
least squares mean (standard error)	-1.00 ( 0.17 )	-1.13 ( 0.16 )	-1.33 ( 0.16 )	-1.14 ( 0.16 )

No statistical analyses for this end point

Secondary: Change in PedsQL emotional distress summary average score

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End point title

Change in PedsQL emotional distress summary average score

End point description

End point type

Secondary

End point timeframe

From Randomization to Week 8

End point values	DBT, Vortioxetine 10 mg	DBT, Vortioxetine 20 mg	DBT, Fluoxetine 20 mg	DBT, Placebo
Number of subjects analysed	124	140	138	137
Units: Units on a scale
least squares mean (standard error)	-0.93 ( 0.18 )	-1.09 ( 0.17 )	-1.33 ( 0.17 )	-1.18 ( 0.17 )

No statistical analyses for this end point

Secondary: Change in Paediatric Quality of Life Enjoyment and Satisfaction Questionnaire (PQ-LES-Q) total scores

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End point title

Change in Paediatric Quality of Life Enjoyment and Satisfaction Questionnaire (PQ-LES-Q) total scores

End point description

(items 1 to 14). The PQ-LES-Q is a patient-rated scale designed to assess satisfaction with life. It is an adaptation of the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q), which is used to measure quality of life in adults. The PQ LES Q consist of 15 items, item 1-14 assess the degree of satisfaction experienced by subjects in various areas of daily functioning and item 15 allows subjects to summarize their experience in a global rating. Each item is rated on a 5-point scale from 1 (very poor) to 5 (very good). The total score range of item 1-14 is 14 to 70, with higher scores indicating greater satisfaction.

End point type

Secondary

End point timeframe

From Randomization to Week 8

End point values	DBT, Vortioxetine 10 mg	DBT, Vortioxetine 20 mg	DBT, Fluoxetine 20 mg	DBT, Placebo
Number of subjects analysed	125	140	137	137
Units: Units on a scale
least squares mean (standard error)	7.62 ( 0.97 )	7.56 ( 0.93 )	9.26 ( 0.94 )	7.06 ( 0.92 )

No statistical analyses for this end point

Secondary: Change in CDRS-R SOMATIC Score

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End point title

Change in CDRS-R SOMATIC Score

End point description

Change in Children Depression Rating Scale - Revised (CDRS-R) Somatic. The CDRS-R has been widely used for the evaluation of children and adolescents with major depressive disorder (MDD). The CDRS-R total score is the sum of the responses to 17 items. Each item is graded on a 5- or 7-point scale. Somatic is one of four subscores defined in the CDRS-R: sum of items 4, 5, 6, 7, 16, 17; score ranges from 6 to 36. The highest possible score indicates the most severe measure of depression.

End point type

Secondary

End point timeframe

From Randomization to Week 8

End point values	DBT, Vortioxetine 10 mg	DBT, Vortioxetine 20 mg	DBT, Fluoxetine 20 mg	DBT, Placebo
Number of subjects analysed	126	139	137	137
Units: units on a scale
least squares mean (standard error)	-5.63 ( 0.46 )	-6.03 ( 0.44 )	-6.79 ( 0.45 )	-5.78 ( 0.44 )

No statistical analyses for this end point

Secondary: Change in CDRS-R BEHAVIOUR Score

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End point title

Change in CDRS-R BEHAVIOUR Score

End point description

Change in Children Depression Rating Scale - Revised (CDRS-R): Behaviour. The CDRS-R has been widely used for the evaluation of children and adolescents with major depressive disorder (MDD). The CDRS-R total score is the sum of the responses to 17 items. Each item is graded on a 5- or 7-point scale. Somatic is one of four subscores defined in the CDRS-R:sum of items 1, 2, 3; score ranges from 3 to 21. The highest possible score indicates the most severe measure of depression.

End point type

Secondary

End point timeframe

From Randomization to Week 8

End point values	DBT, Vortioxetine 10 mg	DBT, Vortioxetine 20 mg	DBT, Fluoxetine 20 mg	DBT, Placebo
Number of subjects analysed	126	139	137	137
Units: Units on a scale
least squares mean (standard error)	-4.32 ( 0.38 )	-4.90 ( 0.36 )	-5.52 ( 0.37 )	-4.73 ( 0.36 )

No statistical analyses for this end point

Secondary: Change in CDRS-R SUBJECTIVE Score

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End point title

Change in CDRS-R SUBJECTIVE Score

End point description

Change in Children Depression Rating Scale - Revised (CDRS-R): Subjective. The CDRS-R has been widely used for the evaluation of children and adolescents with major depressive disorder (MDD). The CDRS-R total score is the sum of the responses to 17 items. Each item is graded on a 5- or 7-point scale. Somatic is one of four subscores defined in the CDRS-R: sum of items 9, 10, 12, 13; score ranges from 4 to 28. The highest possible score indicates the most severe measure of depression.

End point type

Secondary

End point timeframe

From Randomization to Week 8

End point values	DBT, Vortioxetine 10 mg	DBT, Vortioxetine 20 mg	DBT, Fluoxetine 20 mg	DBT, Placebo
Number of subjects analysed	126	139	137	137
Units: Units on a scale
least squares mean (standard error)	-2.41 ( 0.22 )	-2.63 ( 0.21 )	-3.23 ( 0.21 )	-2.66 ( 0.21 )

No statistical analyses for this end point

Secondary: Change General Behaviour Inventory (GBI) Depression Subscale Score assessed by the Child

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End point title

Change General Behaviour Inventory (GBI) Depression Subscale Score assessed by the Child

End point description

The GBI 10-item mania scale is a parent- and subject-rated scale designed to screen for manic symptoms in children and adolescents. The 10 items are rated on a scale from 0 (never or hardly ever) to 3 (very often or almost constantly). The total score ranges from 0 to 30 points, with high scores indicating greater pathology.

End point type

Secondary

End point timeframe

From Randomization to Week 8

End point values	DBT, Vortioxetine 10 mg	DBT, Vortioxetine 20 mg	DBT, Fluoxetine 20 mg	DBT, Placebo
Number of subjects analysed	126	139	137	137
Units: Units on a scale
least squares mean (standard error)	-5.48 ( 0.61 )	-5.55 ( 0.59 )	-6.30 ( 0.59 )	-6.03 ( 0.58 )

No statistical analyses for this end point

Secondary: CGI-S Remission

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End point title

CGI-S Remission

End point description

Remission defined as CGI-S score of 1 or 2.

End point type

Secondary

End point timeframe

From Randomization to Week 8

End point values	DBT, Vortioxetine 10 mg	DBT, Vortioxetine 20 mg	DBT, Fluoxetine 20 mg	DBT, Placebo
Number of subjects analysed	126	139	137	137
Units: Number of patients	26	33	36	24

No statistical analyses for this end point

Secondary: Change in PQ-LES-Q overall Score

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End point title

Change in PQ-LES-Q overall Score

End point description

End point type

Secondary

End point timeframe

From Randomization to Week 8

End point values	DBT, Vortioxetine 10 mg	DBT, Vortioxetine 20 mg	DBT, Fluoxetine 20 mg	DBT, Placebo
Number of subjects analysed	125	140	137	137
Units: Units on a scale
least squares mean (standard error)	0.54 ( 0.08 )	0.43 ( 0.08 )	0.67 ( 0.08 )	0.51 ( 0.08 )

No statistical analyses for this end point

Secondary: Change in PedsQL VAS: sad or blue Score

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End point title

Change in PedsQL VAS: sad or blue Score

End point description

End point type

Secondary

End point timeframe

From Randomization to Week 8

End point values	DBT, Vortioxetine 10 mg	DBT, Vortioxetine 20 mg	DBT, Fluoxetine 20 mg	DBT, Placebo
Number of subjects analysed	124	140	138	137
Units: Units on a scale
least squares mean (standard error)	-1.90 ( 0.26 )	-1.71 ( 0.25 )	-2.45 ( 0.25 )	-2.12 ( 0.24 )

No statistical analyses for this end point

Secondary: Change in PedsQL VAS: angry Score

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End point title

Change in PedsQL VAS: angry Score

End point description

End point type

Secondary

End point timeframe

From Randomization to Week 8

End point values	DBT, Vortioxetine 10 mg	DBT, Vortioxetine 20 mg	DBT, Fluoxetine 20 mg	DBT, Placebo
Number of subjects analysed	124	140	138	137
Units: Units on a scale
least squares mean (standard error)	-0.51 ( 0.23 )	-0.70 ( 0.23 )	-1.01 ( 0.23 )	-0.59 ( 0.23 )

No statistical analyses for this end point

Secondary: Change in PedsQL VAS: worry Score

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End point title

Change in PedsQL VAS: worry Score

End point description

End point type

Secondary

End point timeframe

From Randomization to Week 8

End point values	DBT, Vortioxetine 10 mg	DBT, Vortioxetine 20 mg	DBT, Fluoxetine 20 mg	DBT, Placebo
Number of subjects analysed	124	140	138	137
Units: Units on a scale
least squares mean (standard error)	-0.96 ( 0.25 )	-1.17 ( 0.24 )	-0.91 ( 0.24 )	-1.33 ( 0.24 )

No statistical analyses for this end point

Secondary: Change in PedsQL VAS: tired Score

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End point title

Change in PedsQL VAS: tired Score

End point description

End point type

Secondary

End point timeframe

From Randomization to Week 8

End point values	DBT, Vortioxetine 10 mg	DBT, Vortioxetine 20 mg	DBT, Fluoxetine 20 mg	DBT, Placebo
Number of subjects analysed	124	140	138	137
Units: Units on a scale
least squares mean (standard error)	-1.18 ( 0.29 )	-1.40 ( 0.28 )	-1.55 ( 0.28 )	-1.27 ( 0.28 )

No statistical analyses for this end point

Secondary: Change in PedsQL VAS: pain or hurt Score

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End point title

Change in PedsQL VAS: pain or hurt Score

End point description

End point type

Secondary

End point timeframe

From Randomization to Week 8

End point values	DBT, Vortioxetine 10 mg	DBT, Vortioxetine 20 mg	DBT, Fluoxetine 20 mg	DBT, Placebo
Number of subjects analysed	124	140	138	137
Units: Units on a scale
least squares mean (standard error)	-1.12 ( 0.22 )	-0.97 ( 0.21 )	-0.83 ( 0.21 )	-0.76 ( 0.21 )

No statistical analyses for this end point

Secondary: Change in CDRS-R total score during treatment (at Week 4)

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End point title

Change in CDRS-R total score during treatment (at Week 4)

End point description

End point type

Secondary

End point timeframe

At Week 4

End point values	DBT, Vortioxetine 10 mg	DBT, Vortioxetine 20 mg	DBT, Fluoxetine 20 mg	DBT, Placebo
Number of subjects analysed	137	153	145	149
Units: Units on a scale
least squares mean (standard error)	-14.32 ( 1.14 )	-15.03 ( 1.10 )	-16.25 ( 1.11 )	-13.71 ( 1.09 )

No statistical analyses for this end point

Secondary: Change in CDRS-R total score during treatment (at Week 6)

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End point title

Change in CDRS-R total score during treatment (at Week 6)

End point description

End point type

Secondary

End point timeframe

At Week 6

End point values	DBT, Vortioxetine 10 mg	DBT, Vortioxetine 20 mg	DBT, Fluoxetine 20 mg	DBT, Placebo
Number of subjects analysed	127	145	143	142
Units: Units on a scale
least squares mean (standard error)	-15.43 ( 1.24 )	-17.78 ( 1.19 )	-19.20 ( 1.20 )	-16.71 ( 1.19 )

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

38 months

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

21.0

Reporting group title

Phase A

Reporting group description

Reporting group title

DBT, Vortioxetine 10 mg

Reporting group description

Reporting group title

DBT, Vortioxetine 20 mg

Reporting group description

Reporting group title

DBT, Fluoxetine 20 mg

Reporting group description

Reporting group title

DBT, Placebo

Reporting group description

Serious adverse events	Phase A	DBT, Vortioxetine 10 mg	DBT, Vortioxetine 20 mg	DBT, Fluoxetine 20 mg	DBT, Placebo
Total subjects affected by serious adverse events
subjects affected / exposed	13 / 777 (1.67%)	4 / 147 (2.72%)	7 / 161 (4.35%)	3 / 153 (1.96%)	1 / 154 (0.65%)
number of deaths (all causes)	0	0	0	0	0
number of deaths resulting from adverse events	0	0	0	0	0
Injury, poisoning and procedural complications
Head injury
subjects affected / exposed	0 / 777 (0.00%)	0 / 147 (0.00%)	0 / 161 (0.00%)	1 / 153 (0.65%)	0 / 154 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Lymphadenitis
subjects affected / exposed	1 / 777 (0.13%)	0 / 147 (0.00%)	0 / 161 (0.00%)	0 / 153 (0.00%)	0 / 154 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Reproductive system and breast disorders
Dysmenorrhoea
subjects affected / exposed	1 / 777 (0.13%)	0 / 147 (0.00%)	0 / 161 (0.00%)	0 / 153 (0.00%)	0 / 154 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Psychiatric disorders
Depression
subjects affected / exposed	0 / 777 (0.00%)	0 / 147 (0.00%)	1 / 161 (0.62%)	0 / 153 (0.00%)	0 / 154 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Generalised anxiety disorder
subjects affected / exposed	1 / 777 (0.13%)	0 / 147 (0.00%)	0 / 161 (0.00%)	0 / 153 (0.00%)	0 / 154 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Suicidal behaviour
subjects affected / exposed	1 / 777 (0.13%)	0 / 147 (0.00%)	0 / 161 (0.00%)	0 / 153 (0.00%)	0 / 154 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Suicidal ideation
subjects affected / exposed	6 / 777 (0.77%)	1 / 147 (0.68%)	3 / 161 (1.86%)	2 / 153 (1.31%)	0 / 154 (0.00%)
occurrences causally related to treatment / all	0 / 6	1 / 1	4 / 4	2 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Suicide attempt
subjects affected / exposed	2 / 777 (0.26%)	0 / 147 (0.00%)	1 / 161 (0.62%)	0 / 153 (0.00%)	0 / 154 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Appendicitis
subjects affected / exposed	1 / 777 (0.13%)	1 / 147 (0.68%)	0 / 161 (0.00%)	0 / 153 (0.00%)	0 / 154 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Bronchitis viral
subjects affected / exposed	0 / 777 (0.00%)	1 / 147 (0.68%)	0 / 161 (0.00%)	0 / 153 (0.00%)	0 / 154 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastroenteritis
subjects affected / exposed	0 / 777 (0.00%)	1 / 147 (0.68%)	0 / 161 (0.00%)	0 / 153 (0.00%)	0 / 154 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal viral infection
subjects affected / exposed	0 / 777 (0.00%)	0 / 147 (0.00%)	0 / 161 (0.00%)	0 / 153 (0.00%)	1 / 154 (0.65%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Influenza
subjects affected / exposed	1 / 777 (0.13%)	0 / 147 (0.00%)	0 / 161 (0.00%)	0 / 153 (0.00%)	0 / 154 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Meningitis
subjects affected / exposed	0 / 777 (0.00%)	0 / 147 (0.00%)	1 / 161 (0.62%)	0 / 153 (0.00%)	0 / 154 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia bacterial
subjects affected / exposed	0 / 777 (0.00%)	0 / 147 (0.00%)	1 / 161 (0.62%)	0 / 153 (0.00%)	0 / 154 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Viral upper respiratory tract infection
subjects affected / exposed	0 / 777 (0.00%)	0 / 147 (0.00%)	1 / 161 (0.62%)	0 / 153 (0.00%)	0 / 154 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 3	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Phase A	DBT, Vortioxetine 10 mg	DBT, Vortioxetine 20 mg	DBT, Fluoxetine 20 mg	DBT, Placebo
Total subjects affected by non serious adverse events
subjects affected / exposed	128 / 777 (16.47%)	47 / 147 (31.97%)	57 / 161 (35.40%)	40 / 153 (26.14%)	30 / 154 (19.48%)
Nervous system disorders
Dizziness
subjects affected / exposed	21 / 777 (2.70%)	11 / 147 (7.48%)	7 / 161 (4.35%)	6 / 153 (3.92%)	5 / 154 (3.25%)
occurrences all number	23	14	7	8	6
Headache
subjects affected / exposed	65 / 777 (8.37%)	23 / 147 (15.65%)	20 / 161 (12.42%)	10 / 153 (6.54%)	12 / 154 (7.79%)
occurrences all number	85	37	46	16	19
Gastrointestinal disorders
Diarrhoea
subjects affected / exposed	13 / 777 (1.67%)	5 / 147 (3.40%)	9 / 161 (5.59%)	7 / 153 (4.58%)	5 / 154 (3.25%)
occurrences all number	14	5	10	11	5
Nausea
subjects affected / exposed	28 / 777 (3.60%)	21 / 147 (14.29%)	31 / 161 (19.25%)	10 / 153 (6.54%)	7 / 154 (4.55%)
occurrences all number	31	23	48	16	9
Vomiting
subjects affected / exposed	13 / 777 (1.67%)	7 / 147 (4.76%)	15 / 161 (9.32%)	8 / 153 (5.23%)	1 / 154 (0.65%)
occurrences all number	13	7	20	10	1
Infections and infestations
Nasopharyngitis
subjects affected / exposed	26 / 777 (3.35%)	6 / 147 (4.08%)	10 / 161 (6.21%)	10 / 153 (6.54%)	5 / 154 (3.25%)
occurrences all number	28	7	11	12	7

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

12 Oct 2015

PA1: Revised interim analysis (blinded sample size re-assessment) and sample size sections to reflect that the power for having at least one significant dose with an effect of 4 points instead of 5 points for the primary endpoint is given. Added: Lipids testing

18 Jan 2016

PA2: Inclusion criterion 12: changed urine pregnancy test to blood pregnancy test Exclusion criterion 7: specified that patients who receive formal psychotherapy or CBT are not included in the study. Added that the window between screening and Enrolment was extended for up to 30 days.

05 Jul 2018

PA3: Modified the testing strategy for the primary analysis such that the primary comparison was between the average doses (rather than the individual doses) of vortioxetine to placebo to increase the power of the study

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results: Interventional, randomised, double-blind, placebo-controlled, active reference (fluoxetine), fixed-dose study of vortioxetine in paediatric patients aged 12 to 17 years, with Major depressive disorder (MDD)

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Change in Children Depression Rating Scale - Revised (CDRS-R) total score after treatment

Primary: Change in Children Depression Rating Scale - Revised (CDRS-R) total score after treatment

Secondary: Change in CDRS-R total score during treatment (at Week 2)

Secondary: Change in CDRS-R total score during treatment (at Week 2)

Secondary: Change in CDRS-R MOOD Score

Secondary: Change in CDRS-R MOOD Score

Secondary: CDRS-R response

Secondary: CDRS-R response

Secondary: CDRS-R remission

Secondary: CDRS-R remission

Secondary: Change in General Behaviour Inventory (GBI) depression sub scale score assessed by the Parents

Secondary: Change in General Behaviour Inventory (GBI) depression sub scale score assessed by the Parents

Secondary: Parent Global Assessment–Global Improvement (PGA) score

Secondary: Parent Global Assessment–Global Improvement (PGA) score

Secondary: Change in Symbol Digit Modalities Test (SDMT)

Secondary: Change in Symbol Digit Modalities Test (SDMT)

Secondary: Change in Clinical Global Impression severity of illness (CGI-S) score

Secondary: Change in Clinical Global Impression severity of illness (CGI-S) score

Secondary: Clinical Global Impression - global improvement (CGI-I) score

Secondary: Clinical Global Impression - global improvement (CGI-I) score

Secondary: Change in Children’s Global Assessment Scale (CGAS) score

Secondary: Change in Children’s Global Assessment Scale (CGAS) score

Secondary: Change in Pediatric Quality of Life Inventory (PedsQL) Visual Analogue Scales (VAS): afraid or scared Score

Secondary: Change in Pediatric Quality of Life Inventory (PedsQL) Visual Analogue Scales (VAS): afraid or scared Score

Secondary: Change in PedsQL VAS total average score

Secondary: Change in PedsQL VAS total average score

Secondary: Change in PedsQL emotional distress summary average score

Secondary: Change in PedsQL emotional distress summary average score

Secondary: Change in Paediatric Quality of Life Enjoyment and Satisfaction Questionnaire (PQ-LES-Q) total scores

Secondary: Change in Paediatric Quality of Life Enjoyment and Satisfaction Questionnaire (PQ-LES-Q) total scores

Secondary: Change in CDRS-R SOMATIC Score

Secondary: Change in CDRS-R SOMATIC Score

Secondary: Change in CDRS-R BEHAVIOUR Score

Secondary: Change in CDRS-R BEHAVIOUR Score

Secondary: Change in CDRS-R SUBJECTIVE Score

Secondary: Change in CDRS-R SUBJECTIVE Score

Secondary: Change General Behaviour Inventory (GBI) Depression Subscale Score assessed by the Child

Secondary: Change General Behaviour Inventory (GBI) Depression Subscale Score assessed by the Child

Secondary: CGI-S Remission

Secondary: CGI-S Remission

Secondary: Change in PQ-LES-Q overall Score

Secondary: Change in PQ-LES-Q overall Score

Secondary: Change in PedsQL VAS: sad or blue Score

Secondary: Change in PedsQL VAS: sad or blue Score

Secondary: Change in PedsQL VAS: angry Score

Secondary: Change in PedsQL VAS: angry Score

Secondary: Change in PedsQL VAS: worry Score

Secondary: Change in PedsQL VAS: worry Score

Secondary: Change in PedsQL VAS: tired Score

Secondary: Change in PedsQL VAS: tired Score

Secondary: Change in PedsQL VAS: pain or hurt Score

Secondary: Change in PedsQL VAS: pain or hurt Score

Secondary: Change in CDRS-R total score during treatment (at Week 4)

Secondary: Change in CDRS-R total score during treatment (at Week 4)

Secondary: Change in CDRS-R total score during treatment (at Week 6)

Secondary: Change in CDRS-R total score during treatment (at Week 6)

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
Interventional, randomised, double-blind, placebo-controlled, active reference (fluoxetine), fixed-dose study of vortioxetine in paediatric patients aged 12 to 17 years, with Major depressive disorder (MDD)