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
- Registration Number
- NCT02871297
- Lead Sponsor
- H. Lundbeck A/S
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 662
- The participant is a male or female child aged ≥7 and <12 years or adolescent aged ≥12 and ≤18 years in the lead-in study (12709A and 12710A).
- The participant must have completed Study 12709A or 12710A (Visit 12, Completion Visit) immediately prior to enrolment into this extension study.
- The participant had a primary diagnosis of MDD at entry in study 12709A or 12710A, diagnosed according to DSM-5™.
- The participant is indicated for long-term treatment with vortioxetine according to the clinical opinion of the Investigator.
- For participants aged ≥7 and ≤17 years at the Baseline visit; the participant is able to understand the Informed Assent Form, and parent(s)/legal representative(s) are able to read and understand the Informed Consent Form.
- For participants who turned 18 years during the lead-in study 12710A; the participant has signed the Informed Consent Form.
- The participant has been diagnosed with another psychiatric disorder (for example mania, bipolar disorder, schizophrenia or any psychotic disorder) during study 12709A or 12710A.
- The participant has an attention-deficit/hyperactivity disorder (ADHD) that requires a pharmacological treatment other than a stimulant medication.
Other protocol-defined inclusion and exclusion criteria may apply
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Vortioxetine Vortioxetine Vortioxetine tablets for 26 weeks. Single dose of vortioxetine oral drops (only a subset of participants).
- Primary Outcome Measures
Name Time Method Number of Participants With Treatment-Emergent Adverse Events (TEAEs) 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 defined as an AE that started or increased in intensity on or after the date of first dose of study drug in this study 12712A. A summary of serious and non-serious AEs regardless of causality is located in 'Reported Adverse Events module'.
- Secondary Outcome Measures
Name Time Method Change From Baseline in Children Depression Rating Scale - Revised (CDRS-R) Total Score at Week 26 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 (MMRM) approach.
Adolescents (12-18 Years): Change From Baseline in BRIEF-SR Using the MI Score at Week 26 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 detailed in T-score conversion tables for BRIEF-SR. The conversion was based on gender and the age group. T-scores ranged between 31 to 100, with a lower score indicating better functioning.
Number of Participants With Response to the Palatability Questionnaire 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, good, or very good. The oral drops were considered acceptable if the mean hedonic scores were ≤3 for each aspect of palatability (taste, aftertaste, smell, and mouthfeel).
Time to First Relapse Baseline up to Week 26 Relapse was defined as a total score ≥40 on the CDRS-R. 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).
Change From Baseline in Children's Global Assessment Scale (CGAS) Score at Week 26 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.
Change From Baseline in Pediatric Quality of Life Inventory Present Functioning Visual Analogue Scale (PedsQL VAS) Total Score at Week 26 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.
Time to First Loss of Remission Baseline up to Week 26 Remission was defined as a total score ≤28 on the CDRS-R. 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).
Change From Baseline in Clinical Global Impression - Severity of Illness (CGI-S) Score at Week 26 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.
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 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 scales. GEC score was calculated as the sum of index scores ranging from 72-216; higher scores indicating greater impairment in executive functions. Raw scores converted to T-scores as detailed in T-score conversion tables for BRIEF-P. Conversion was based on gender and age group. T-scores ranged between 30 to 101, with a lower score indicating better functioning.
Clinical Global Impression - Global Improvement (CGI-I) Score 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.
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 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. GEC score was calculated as the sum of index scores and ranges from 80-240 with higher scores indicating greater impairment in functions. Raw scores converted to T-scores as detailed in T-score conversion tables for BRIEF-SR. The conversion was based on gender and the age group. T-scores ranged between 29 to 104, with a lower score indicating better functioning.
Children (7-11 Years): Change From Baseline in BRIEF-P Using the MI Score at Week 26 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 detailed in T-score conversion tables for BRIEF-P. The conversion was based on gender and the age group. T-scores ranged between 30 to 98, with a lower score indicating better functioning.
Number of Participants With Response to the Acceptability Questionnaire 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 questions regarding acceptability.
Trial Locations
- Locations (78)
Cape Trial Centre
🇿🇦Bellville, Cape Town, South Africa
NHS Greater Glasgow and Clyde Glasgow Clinical Research Facility-Queen Elizabeth University Hospi...
🇬🇧Glasgow, United Kingdom
Hospital General Universitario Gregorio Maranon
🇪🇸Madrid, Spain
Unidad de Salud Mental Infanto-Juvenil (USMI-J) Edificio de Consultas Externas. Hospital MarAtimo
🇪🇸Torremolinos, Malaga, Spain
Child and Adolescent Neurology and Psychiatry Clinic
🇷🇸Belgrade, Serbia
Alder Hey Hospital
🇬🇧Liverpool, United Kingdom
Daily Hospital for Children and Adolescents
🇷🇸Pantelej-Nis, Serbia
Hospital Universitario Fundacion Alcorcon
🇪🇸Alcorcon, Madrid, Spain
University Hospital Cleveland Medical Center Division of Child and Adolescent Psychiatry
🇺🇸Cleveland, Ohio, United States
Paediatric Sleep Research Inc.
🇨🇦Toronto, Ontario, Canada
The University of Arizona Sarver Heart Center (SHC)
🇺🇸Tucson, Arizona, United States
University of Cincinnati Medical Center
🇺🇸Cincinnati, Ohio, United States
MHAT Targovishte AD
🇧🇬Targovishte, Bulgaria
Diagnostic Consultative Center Mladost-M Varna OOD
🇧🇬Varna, Bulgaria
E.S.E. Hospital Mental de Antioquia HOMO
🇨🇴Bello, Antioquia, Colombia
Centro de Investigaciones y Proyectos en Neurociencias CIPNA LTDA IPS.
🇨🇴Barranquilla, Atlantico, Colombia
Centro de investigaciones del Sistema Nervioso SAS Grupo CISNE SAS
🇨🇴Bogota, DC, Colombia
Psynapsis Salud Mental S.A.
🇨🇴Pereira, Risaralda, Colombia
Marienthali Kliinik
🇪🇪Tallinn, Estonia
Cabinet Psyche
🇫🇷Douai, Nord, France
Centre Medical Ambroise Pare
🇫🇷Elancourt, France
Klinik fur Kinderneurologie und Sozialpadiatrie Kinderzentrum Maulbronn gGmbH
🇩🇪Maulbronn, Germany
CHU de Nantes - Hopital Hotel Dieu
🇫🇷Nantes Cedex 1, France
Rheinhessen-Fachklinik Mainz, Kinder und Jugendpsychiatri
🇩🇪Mainz, Germany
Univ. Freiburg
🇩🇪Freiburg, Baden-Wurttemberg, Germany
University Hospital Tuebingen -
🇩🇪Tuebingen, Germany
Vadaskert Child Psychiatric Hospital and Outpatient
🇭🇺Budapest, Hungary
Bekes Megyei Kozponti Korhaz Pandy Kalman Tagkorhaza
🇭🇺Gyula, Hungary
Ramat Chen - Mental Health Clinic
🇮🇱Tel Aviv, Israel
Scientific Institute Fondazione Stella Maris
🇮🇹Calambrone, Pisa, Italy
U.O.C. Neuropsichiatria Infantile - IRCCS Istituto Giannina Gaslini
🇮🇹Genova, Italy
Soon Chun Hyang University Hospital Cheonan
🇰🇷Cheonan-si, Chungcheongnam-do, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Hospital Gintermuiza
🇱🇻Jelgava, Latvia
Linda Keruze's Psychiatric Center, LLC
🇱🇻Liepaja, Latvia
Children Hospilal -Gailezers
🇱🇻Riga, Latvia
Sigulda Hospital Outpatient Clinic
🇱🇻Sigulda, Latvia
Instituto Nacional de Pediatria (INP) (National Institute of Pediatrics)
🇲🇽Ciudad de Mexico, Distrito Federal, Mexico
Clinica Cemelli
🇲🇽Guadalajara, Jalisco, Mexico
Roberto Zepeda Sanchez
🇲🇽Guadalajara, Jalisco, Mexico
CRI Centro Regiomontano de Investigacion SC
🇲🇽Monterrey, Nuevo Leon, Mexico
B & B Investigaciones Medicas, SC
🇲🇽Mazatlan, Sinaloa, Mexico
BIND Investigaciones S.C
🇲🇽San Luis Potosi, Mexico
Centrum Badan Klinicznych PI-House Sp. z o.o.
🇵🇱Gdansk, Poland
Spectrum Centrum Psychiatrii Specjalistyczny Gabinet Psychiatryczny
🇵🇱Lublin, Poland
Przychodnia Syntonia Poradnia Zdrowia Psychicznego
🇵🇱Kielce, Poland
Filip Rybakowski Specjalistyczna Praktyka Lekarska
🇵🇱Poznan, Poland
Specjalistyczny Szpital im. dra A. Sokolowskiego w Walbrzychu
🇵🇱Walbrzych, Poland
Centrum Neuropsychiatrii Neuromed
🇵🇱Wroclaw, Poland
Medicorehabilitation Research Center Phoenix
🇷🇺Rostov-On-Don, Rostov State, Russian Federation
Stavropol Region Psychiatric Hospital No.2
🇷🇺Stavropol, Stavropol Region, Russian Federation
Arkhangelsk Regional Clinical Mental Hospital
🇷🇺Arkhangelsk, Russian Federation
State Budgetary Healthcare Institution of Sverdlovsk Region ¿Sverdlovsk Regional Clinical Psychi...
🇷🇺Ekaterinburg, Russian Federation
GUZ Engels Psychiatric Hospital
🇷🇺Engels, Russian Federation
Lipetsk Regional Psychoneurological Hospital
🇷🇺Lipetsk, Russian Federation
State Budgetary Healthcare Institution (SBHI) Specialized Clinical Psychiatric Hospital 1 of the ...
🇷🇺Krasnodar, Russian Federation
Nizhny Novgorod Region State Institution Of Healthcare Clinical Psychiatric Hospital 1 Of Nizhny ...
🇷🇺Nizhny Novgorod, Russian Federation
LLC City Neurological Center Sibneuromed
🇷🇺Novosibirsk, Russian Federation
Saratov State Medical University
🇷🇺Saratov, Russian Federation
Rostov State Medical University of the Minzdravsotsrazvitiya of Russia
🇷🇺Rostov-on-Don, Russian Federation
City Psychiatric Hospital No.3 named after I.I. Skvortsov-Stepanov
🇷🇺St-Petersburg, Russian Federation
Guz Saratov Regional Psychiatric Hospital St. Sofii
🇷🇺Saratov, Russian Federation
Yaroslavl Regional Clinical Psychiatry Hospital
🇷🇺Yaroslavl, Russian Federation
Nebbiolo LLC
🇷🇺Tomsk, Russian Federation
Kansas University School of Medicine-Wichita
🇺🇸Wichita, Kansas, United States
Centro para el Desarrollo de la Medicina y de Asistencia Medica Especializada S.C
🇲🇽Culiacan De Rosales, Sinaloa, Mexico
Sciaf Ulss 16 Padova
🇮🇹Padova, Regione Veneto, Italy
Hospital Trust-University of Cagliari
🇮🇹Cagliari, Italy
Dip.Sc.Biomediche, Odont. e Imm.Funz.li, AOU Policlinico G. Martino
🇮🇹Messina, Italy
University Federico II Of Naples
🇮🇹Napoli, Italy
Prywatne Gabinety Lekarskie Promedicus
🇵🇱Bialystok, Podlaskie, Poland
University Clinical Center Kragujevac
🇷🇸Kragujevac, Serbia
Ukrainian Research Institute Of Social, Forensic Psychiatry And Drug Abuse, Kiev City Psychoneuro...
🇺🇦Kyiv, Ukraine
Odessa Regional Medical Centre of Mental Health
🇺🇦Odessa, Ukraine
Ternopil Regional Clinical Municipal Psycho-Neurological Hospital, Ternopil State Medical Univers...
🇺🇦Ternopil, Ukraine
Institute of Mental Health
🇷🇸Belgrade, Serbia
Maltsev Poltava Regional Clinical Psychiatric Hospital, Higher State Educational Institution Of U...
🇺🇦Poltava, Ukraine
Clinical Center of Vojvodina - Clinic of Psychiatry
🇷🇸Novi Sad, Serbia