Active Reference (Fluoxetine) Fixed-dose Study of Vortioxetine in Paediatric Patients Aged 12 to 17 Years With Major Depressive Disorder (MDD)

Depressive Disorder, Major Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02709746
• Other study ID #: 12710A
• Secondary ID: 2008-005354-20
• Status: Completed
• Phase: Phase 3
• Start date: May 2016
• Est. completion date: July 30, 2019

Study information

• Verified date: August 2020
• Source: H. Lundbeck A/S
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Evaluating the efficacy of vortioxetine 10 mg/day and 20 mg/day versus placebo on depressive symptoms in adolescents (age ≥12 and ≤17 years) with a DSM-5™ (Diagnostic and Statistical Manual of Mental Disorders, 5th edition) diagnosis of Major depressive disorder (MDD).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 784
• Est. completion date: July 30, 2019
• Est. primary completion date: July 2, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 17 Years

Eligibility

Inclusion Criteria:

• The patient is a male or female, aged =12 and =17 years at Screening (patients who turn 18 years during the study will be allowed to continue in the study).

• The patient has Major depressive disorder (MDD), diagnosed according to DSM-5™.

• The patient has a Children Depression Rating Scale - Revised (CDRS-R) total score =45 at the Screening Visit and at the Baseline.

• The patient has a Clinical Global Impression - Severity of Illness (CGI-S) score =4 at the Screening Visit and at the Baseline

• The patient has provided assent to participation and parent(s)/legal representative (s) signed the Informed Consent Form.

Exclusion Criteria:

• The patient has participated in a clinical study <30 days prior to the Screening Visit.

Other protocol defined inclusion and exclusion criteria may apply

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Major

Intervention

Drug:
• Vortioxetine 10 mg/day
10 mg/day, encapsulated tablet (with addition of lower initial dose levels). Based on tolerability the dose may be reduced by 5 mg/day. No dose increase will be allowed
• Vortioxetine 20 mg/day
20 mg/day, encapsulated tablet (with addition of lower initial dose levels). Based on tolerability the dose may be reduced by 5 mg/day. No dose increase will be allowed
• Fluoxetine 20 mg/day
20 mg/day, encapsulated tablet (with addition of lower initial dose levels). Based on tolerability the dose may be reduced by 10 mg/day. No dose increase will be allowed

Other:
• Placebo
Encapsulated tablet

Locations

Country	Name	City	State
Bulgaria	BG1023	Targovishte
Bulgaria	BG1025	Varna
Canada	CA1036 University of Calgary	Calgary
Canada	CA1038	Toronto
Colombia	CO1003	Barranquilla
Colombia	CO1001	Bello
Colombia	CO1004	Bogotá
Colombia	CO1002	Pereira
Estonia	EE1007	Tallinn
Estonia	EE1015	Viljandi
France	FR1041	Douai
France	FR1017	Elancourt
France	FR1009	Nantes
Germany	DE1078	Freiburg
Germany	DE1034	Mainz
Germany	DE1077	Mannheim
Germany	DE1081	Maulbronn
Germany	DE1076	Tübingen
Hungary	HU1023	Budapest
Hungary	HU1020	Gyula
Italy	IT1075	Cagliari
Italy	IT1073	Genova
Italy	IT1029	Messina
Italy	IT1068	Napoli
Italy	IT1074	Padova
Italy	IT1070	Pisa
Italy	IT1072 Osppedale Bambin gesu	Rome
Korea, Republic of	KR1035	Cheonan
Korea, Republic of	UA1037	Gyeongsang
Korea, Republic of	KR1032	Seoul
Korea, Republic of	KR1038	Seoul
Latvia	LV1002	Jelgava
Latvia	LV1008	Liepaja
Latvia	LV1009	Riga
Latvia	LV1007	Sigulda
Mexico	MX1003	Ciudad de mexico
Mexico	MX1014	Culiacán
Mexico	MX1011	Guadalajara
Mexico	MX1013	Guadalajara
Mexico	MX1022	Guadalajara
Mexico	MX1023	Mazatlán
Mexico	MX1001	Nuevo León
Poland	PL1002	Bialystok
Poland	PL1050	Gdansk
Poland	PL1068	Kielce
Poland	PL1057	Lublin
Poland	PL1052	Poznan
Poland	PL1054	Wabrzezno
Poland	PL1051	Wroclaw
Russian Federation	RU1009	Arkhangel'sk
Russian Federation	RU1016	Ekaterinburg
Russian Federation	RU1059	Engel's
Russian Federation	RU1046	Krasnodar
Russian Federation	RU1011	Lipetsk
Russian Federation	RU1004	Nizhniy Novgorod
Russian Federation	RU1010	Novosibirsk
Russian Federation	RU1012	Rostov on Don
Russian Federation	RU1044	Rostov-na-Donu
Russian Federation	RU1013	Saratov
Russian Federation	RU1038	Saratov
Russian Federation	RU1030	St.Petersburg
Russian Federation	RU1057	Tomsk
Russian Federation	RU1048	Tonnel'nyy
Serbia	RS1010	Belgrad
Serbia	RS1006 Clinic of Neurology and Psychiatry for Children and Adolescents	Belgrade
Serbia	RS1011	Kragujevac
Serbia	RS1003	Niš
Serbia	RS1007	Novi Sad
South Africa	ZA1019	Cape Town
South Africa	ZA1022	Randburg
South Africa	ZA1023	Sandton
Spain	ES1041	Alcorcon
Spain	ES1044	Madrid
Spain	ES1043	Pamplona
Spain	ES1018 Hospital de Sabadell	Sabadell
Spain	ES1040	Torremolinos
Ukraine	UA1002	Kyiv
Ukraine	UA1019	Odessa
Ukraine	UA1001	Poltava
Ukraine	UA1004	Ternopil'
United Kingdom	GB1051	Glasgow
United Kingdom	GB1047	Liverpool
United States	US1009	Atlanta	Georgia
United States	US1328	Austin	Texas
United States	US1015	Baltimore	Maryland
United States	US1312	Berlin	New Jersey
United States	US1051	Cincinnati	Ohio
United States	US1054	Cleveland	Ohio
United States	US1385 Ericksen Research And Development	Clinton	Mississippi
United States	US1062	Costa Mesa	California
United States	US1064	Creve Coeur	Missouri
United States	US1369	Dothan	Alabama
United States	US1387	Downey	California
United States	US1114	Escondido	California
United States	US1217	Gainesville	Florida
United States	US1118	Glendale	California
United States	US1123	Imperial	California
United States	US1261	Lake Charles	Louisiana
United States	US1310	Little Rock	Arkansas
United States	US1160 Renew Behavioral Health, Inc.	Long Beach	California
United States	US1313	Marietta	Georgia
United States	US1334	Middleburg Heights	Ohio
United States	US1311	Naperville	Illinois
United States	US1315	Naperville	Illinois
United States	US1317	New York	New York
United States	US1314	O'Fallon	Missouri
United States	US1103	Oak Brook	Illinois
United States	US1323	Oklahoma City	Oklahoma
United States	US1329	Oklahoma City	Oklahoma
United States	US1368	Orange	California
United States	US1229	Orange City	Florida
United States	US1308	Orem	Utah
United States	US1370	Panorama City	California
United States	US1320	Plano	Texas
United States	US1222	Princeton	New Jersey
United States	US1309	Richmond	Virginia
United States	US1171	Rochester	New York
United States	US1266	Saint Charles	Missouri
United States	US1162	San Antonio	Texas
United States	US1190	Staten Island	New York
United States	US1333	Tucson	Arizona
United States	US1133	Washington	District of Columbia
United States	US1386	Wichita	Kansas
United States	US1351	Wildomar	California

Sponsors (2)

Lead Sponsor	Collaborator
H. Lundbeck A/S	Takeda

Countries where clinical trial is conducted

United States,  Bulgaria,  Canada,  Colombia,  Estonia,  France,  Germany,  Hungary,  Italy,  Korea, Republic of,  Latvia,  Mexico,  Poland,  Russian Federation,  Serbia,  South Africa,  Spain,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Children Depression Rating Scale - Revised (CDRS-R) Total Score After Treatment	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).	From Randomization to Week 8
Secondary	Change in CDRS-R Total Score During Treatment (at Week 2)	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'.	At week 2
Secondary	Change in CDRS-R Total Score During Treatment (at Week 4)	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).	At week 4
Secondary	Change in CDRS-R Total Score During Treatment (at Week 6)	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).	At week 6
Secondary	Change in CDRS-R Mood Score	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.	From randomization to Week 8
Secondary	Change in CDRS-R Somatic Score	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.	From Randomization to Week 8
Secondary	Change in CDRS-R Subjective Score	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. Subjective 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.	From Randomization to Week 8
Secondary	Change in CDRS-R Behaviour Score	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. behaviour 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.	From Randomization to Week 8
Secondary	CDRS-R Response	Children Depression Rating Scale - Response: defined as a >= 50% decrease in CDRS-R total score, calculated as (change from baseline [Randomization])/(baseline value - 17).	From Randomization to Week 8
Secondary	CDRS-R Remission	Remission is defined as a CDRS-R total score <= 28.	From Randomization to Week 8
Secondary	Change in General Behaviour Inventory (GBI) Depression Sub Scale Score Assessed by the Parents	Using the 10-item depression subscale, assessed by parent (PGBI-10D). Change from randomization to Week 8 in GBI Total Parent/Guardian Version Depression score. 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.	From randomization to week 8
Secondary	Change General Behaviour Inventory (GBI) Depression Subscale Score Assessed by the Child	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.	From randomization to Week 8
Secondary	Parent Global Assessment-Global Improvement (PGA) Score	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).	From Randomization to Week 8
Secondary	Change in Symbol Digit Modalities Test (SDMT)	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).	From Randomization to Week 8
Secondary	Change in Clinical Global Impression Severity of Illness (CGI-S) Score	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).	From Randomization to Week 8
Secondary	Clinical Global Impression - Global Improvement (CGI-I) Score	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.	From Randomization to Week 8
Secondary	CGI-S Remission	Remission defined as CGI-S score of 1 or 2.	From Randomization to Week 8
Secondary	Change in Children's Global Assessment Scale (CGAS) Score	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.	From Randomization to Week 8
Secondary	Change in Pediatric Quality of Life Inventory (PedsQL) Visual Analogue Scales (VAS): Afraid or Scared (Anxiety) Score	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 (0-10 points). The patients are asked to mark on the line how they feel. A lower value represents a better outcome.	From Randomization to Week 8
Secondary	Change in PedsQL VAS: Sad or Blue (Sadness) Score	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 (0-10 points). The patients are asked to mark on the line how they feel. A lower value represents a better outcome.	From Randomization to Week 8
Secondary	Change in PedsQL VAS: Angry Score	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 (0-10 points). The patients are asked to mark on the line how they feel. A lower value represents a better outcome.	From Randomization to Week 8
Secondary	Change in PedsQL VAS: Worry Score	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 (0-10 points). The patients are asked to mark on the line how they feel. A lower value represents a better outcome.	From Randomization to Week 8
Secondary	Change in PedsQL VAS: Tired (Fatigue) Score	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 (0-10 points). The patients are asked to mark on the line how they feel. A lower value represents a better outcome.	From Randomization to week 8
Secondary	Change in PedsQL VAS: Pain or Hurt Score	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 (0-10 points). The patients are asked to mark on the line how they feel. A lower value represents a better outcome.	From Randomization to Week 8
Secondary	Change in PedsQL VAS Total Average Score	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 (0-10 points). The patients are asked to mark on the line how they feel. The total score is the average of all 6 items. A lower value represents a better outcome.	From Randomization to week 8
Secondary	Change in PedsQL Emotional Distress Summary Average Score	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 (0-10 points). The patients are asked to mark on the line how they feel. The average emotional distress summary score is the mean of the anxiety, sadness, anger, and worry items. A lower value represents a better outcome.	From Randomization to week 8
Secondary	Change in Paediatric Quality of Life Enjoyment and Satisfaction Questionnaire (PQ-LES-Q) Total Scores	PQ-LES-Q total score (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 (this outcome measurement) is 14 to 70, with higher scores indicating greater satisfaction.	From Randomization to Week 8
Secondary	Change in PQ-LES-Q Overall Score	PQ-LES-Q overall evaluation score (item 15). 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 (this outcome measurement). Item 15 is rated on a 5-point scale from 1 (very poor) to 5 (very good).	From Randomization to Week 8