Depression
Conditions
Brief summary
The purpose of this study is to find out if vortioxetine is better than placebo (sugar pills) in preventing depression in children who improved when treated with vortioxetine.
Detailed description
The study consists of a 12-week open-label, flexible-dose treatment period with vortioxetine, followed by a 26-week, randomized, double-blind, fixed-dose, placebo-controlled relapse-prevention period. There will be a safety follow up 4 weeks after the end of the 26-week double-blind treatment period. The study population will include 'de novo' participants as well as 'rollover' participants from other paediatric vortioxetine studies 12709A (NCT02709655) and 12712A (NCT02871297), who, in the investigator's opinion, could benefit from continued treatment with vortioxetine.
Interventions
DRUGVortioxetine
Tablets
DRUGPlacebo
Tablets
Sponsors
H. Lundbeck A/S
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
7 Years to 11 Years
Healthy volunteers
No
Inclusion criteria
De novo participants * The participant has a primary diagnosis of MDD according to DSM-5™ although co-morbid anxiety disorders will be permitted (except Post Traumatic Stress Disorder (PTSD) and Obsessive Compulsive Disorder (OCD)). * The participant has a CDRS-R total score ≥45 at the Screening and Baseline Visits. * The participant has a Clinical Global Impression - Severity of Illness (CGI-S) ≥4 at the Screening and Baseline Visit
Exclusion criteria
* The participant receives ongoing current psychotherapy that is planned to be intensified. Interpersonal psychotherapy (IPT) or cognitive behavioural therapy (CBT) are not allowed. * The participant presents with, or has a history of, an Axis I (DSM-5TM) diagnosis of Bipolar Disorder, PTSD, OCD, Autism, Pervasive Developmental Disorder (PDD), or Schizophrenia or Schizoaffective Disorder. * The participant has a diagnosis of attention-deficit/hyperactivity disorder (ADHD) and is not maintained on a stable dose of a methylphenidate or amphetamine for a minimum of 4 weeks prior to the study treatment. * The participant has attempted suicide or is at significant risk of suicide Other inclusion and
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Relapse in the Double-blind Period | From randomization to Week 26 in the double-blind treatment period | Relapse was defined as either a total score ≥40 on the Children Depression Rating Scale Revised Version (CDRS-R) with a history of 2 weeks of clinical deterioration, or clinical deterioration as judged by the clinician. The CDRS-R is rated by a clinician following interviews with the child and parent and consists of 17 items out of which 3 items rate nonverbal observations (listless speech, hypoactivity, and depressed affect). Fourteen items are rated on a 7-point scale from 1 to 7, and 3 items (sleep disturbance, appetite disturbance, and listless speech) are scored on a 5-point scale from 1 to 5. A rating of 1 indicates normal functioning and a higher number indicates a greater degree of depression. The total score ranges from 17 (normal) to 113 (severe depression). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Children's Depression Rating Scale - Revised Version (CDRS-R) Total Score at Week 26 | Baseline, Week 26 | The CDRS-R is a clinician-rated scale to measure the severity of depression in children and adolescents. The CDRS-R is rated by a clinician following interviews with the child and parent and consists of 17 items out of which 3 items rate nonverbal observations (listless speech, hypoactivity, and depressed affect). Fourteen items are rated on a 7-point scale from 1 to 7, and 3 items (sleep disturbance, appetite disturbance, and listless speech) are scored on a 5-point scale from 1 to 5. A rating of 1 indicates normal functioning and a higher number indicates a greater degree of depression. The total score ranges 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). |
| Relapse Rate in the Double-blind Period: Percentage of Participants With Relapse | From randomization to Week 26 in the double-blind treatment period | Relapse was defined as either a total score ≥40 on the CDRS-R with a history of 2 weeks of clinical deterioration, or clinical deterioration as judged by the clinician. The CDRS-R is rated by a clinician following interviews with the child and parent and consists of 17 items out of which 3 items rate nonverbal observations (listless speech, hypoactivity, and depressed affect). Fourteen items are rated on a 7-point scale from 1 to 7, and 3 items (sleep disturbance, appetite disturbance, and listless speech) are scored on a 5-point scale from 1 to 5. A rating of 1 indicates normal functioning and a higher number indicates a greater degree of depression. The total score ranges from 17 (normal) to 113 (severe depression). |
| Change From Baseline in Paediatric Quality of Life Enjoyment and Satisfaction Questionnaire (PQ-LES-Q) Total Score (Items 1 to 14) at Week 26 | Baseline, Week 26 | The PQ-LES-Q is a participant-rated scale designed to assess satisfaction with life. It is an adaptation of the Quality of Life Enjoyment and Satisfaction Questionnaire, which is used to measure quality of life in adults. The PQ-LES-Q consist of 15 items, item 1 to 14 assess the degree of satisfaction experienced by participants in various areas of daily functioning, and item 15 allows participants to summarise 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 to 14 is 14 to 70, with higher scores indicating greater satisfaction. |
| Plasma Concentration of Vortioxetine | From randomization to Week 26 in the double-blind treatment period | — |
| Clinical Global Impression - Global Improvement (CGI-I) Score at Week 26 | 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). |
Countries
Colombia, Latvia, Mexico, Poland, Russia, Ukraine, United States
Participant flow
Recruitment details
The study population included de novo participants as well as rollover participants from other paediatric vortioxetine studies (Studies 12709A \[NCT02709655\] and 12712A \[NCT02871297\]) who, in the investigator's opinion, would benefit from continued treatment with vortioxetine.
Pre-assignment details
Rollover participants from Study 12709A enrolled to the open-label period and rollover participants (remitters) from Study 12712A randomized to the double-blind period. Overall, 35 participants were treated in this study: 33 participants in the open-label period (24 de novo participants and 9 rollover participants from Study 12709A) and 4 participants in the double-blind period (2 of whom rolled-over from Study 12712A).
Participants by arm
| Arm | Count |
|---|---|
| Open-Label Treatment: Vortioxetine Participants initiated treatment with vortioxetine tablets 5 milligrams (mg)/day orally for the first 2 days and thereafter they received 10 mg/day vortioxetine. Based on the response and dose-limiting adverse events (AEs), vortioxetine dose could be up- or down-titrated with 5 mg/day to a maximum of 20 mg/day during the first 8 weeks. From Week 8 to Week 12, the dose remained fixed. | 33 |
| Double-Blind Relapse Prevention: Vortioxetine Participants continued on the same fixed dose of vortioxetine as during the end of the open-label period for 26 weeks in the double-blind relapse prevention period. | 2 |
| Double-Blind Relapse Prevention: Placebo Participants received placebo for 26 weeks in the double-blind relapse prevention period. | 2 |
| Total | 37 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Double-Blind (26 Weeks) | Based on Sponsor Information of Results From Vortioxetine Study | 0 | 1 | 1 |
| Double-Blind (26 Weeks) | Study Terminated by Sponsor | 0 | 0 | 1 |
| Open-Label (12 Weeks) | Adverse Event | 1 | 0 | 0 |
| Open-Label (12 Weeks) | Based on Sponsor Information of Results From Vortioxetine Study | 15 | 0 | 0 |
| Open-Label (12 Weeks) | Lack of Efficacy | 1 | 0 | 0 |
| Open-Label (12 Weeks) | Sponsor Decision | 4 | 0 | 0 |
| Open-Label (12 Weeks) | Study Terminated by Sponsor | 5 | 0 | 0 |
| Open-Label (12 Weeks) | Withdrawal by Subject | 2 | 0 | 0 |
Baseline characteristics
| Characteristic | Open-Label Treatment: Vortioxetine | Total | Double-Blind Relapse Prevention: Placebo | Double-Blind Relapse Prevention: Vortioxetine |
|---|---|---|---|---|
| Age, Customized Double-Blind Relapse Prevention Adolescents (12-17 years) | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized Double-Blind Relapse Prevention Children (2-11 years) | 0 Participants | 4 Participants | 2 Participants | 2 Participants |
| Age, Customized Open-Label Treatment Adolescents (12-17 years) | 6 Participants | 6 Participants | 0 Participants | 0 Participants |
| Age, Customized Open-Label Treatment Children (2-11 years) | 27 Participants | 27 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Double-Blind Relapse Prevention Hispanic or Latino | 0 Participants | 3 Participants | 1 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Double-Blind Relapse Prevention Not Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Double-Blind Relapse Prevention Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Open-Label Treatment Hispanic or Latino | 18 Participants | 18 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Open-Label Treatment Not Hispanic or Latino | 15 Participants | 15 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Open-Label Treatment Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Double-Blind Relapse Prevention Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Double-Blind Relapse Prevention Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Double-Blind Relapse Prevention Other | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Double-Blind Relapse Prevention White | 0 Participants | 2 Participants | 2 Participants | 0 Participants |
| Race/Ethnicity, Customized Open-Label Treatment Asian | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Open-Label Treatment Black or African American | 3 Participants | 3 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Open-Label Treatment Other | 16 Participants | 16 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Open-Label Treatment White | 13 Participants | 13 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Double-Blind Relapse Prevention Female | 0 Participants | 2 Participants | 1 Participants | 1 Participants |
| Sex: Female, Male Double-Blind Relapse Prevention Male | 0 Participants | 2 Participants | 1 Participants | 1 Participants |
| Sex: Female, Male Open-Label Treatment Female | 18 Participants | 18 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Open-Label Treatment Male | 15 Participants | 15 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 33 | 0 / 2 | 0 / 2 |
| other Total, other adverse events | 8 / 33 | 1 / 2 | 0 / 2 |
| serious Total, serious adverse events | 0 / 33 | 0 / 2 | 0 / 2 |
Outcome results
Primary
Time to Relapse in the Double-blind Period
Relapse was defined as either a total score ≥40 on the Children Depression Rating Scale Revised Version (CDRS-R) with a history of 2 weeks of clinical deterioration, or clinical deterioration as judged by the clinician. The CDRS-R is rated by a clinician following interviews with the child and parent and consists of 17 items out of which 3 items rate nonverbal observations (listless speech, hypoactivity, and depressed affect). Fourteen items are rated on a 7-point scale from 1 to 7, and 3 items (sleep disturbance, appetite disturbance, and listless speech) are scored on a 5-point scale from 1 to 5. A rating of 1 indicates normal functioning and a higher number indicates a greater degree of depression. The total score ranges from 17 (normal) to 113 (severe depression).
Time frame: From randomization to Week 26 in the double-blind treatment period
Population: Due to the early termination of study and limited number of participants who completed the double-blind period, the efficacy analyses were not performed and data were not collected for this outcome measure.
Secondary
Change From Baseline in Children's Depression Rating Scale - Revised Version (CDRS-R) Total Score at Week 26
The CDRS-R is a clinician-rated scale to measure the severity of depression in children and adolescents. The CDRS-R is rated by a clinician following interviews with the child and parent and consists of 17 items out of which 3 items rate nonverbal observations (listless speech, hypoactivity, and depressed affect). Fourteen items are rated on a 7-point scale from 1 to 7, and 3 items (sleep disturbance, appetite disturbance, and listless speech) are scored on a 5-point scale from 1 to 5. A rating of 1 indicates normal functioning and a higher number indicates a greater degree of depression. The total score ranges from 17 (normal) to 113 (severe depression).
Time frame: Baseline, Week 26
Population: Due to the early termination of study and limited number of participants who completed the double-blind period, the efficacy analyses were not performed and data were not collected for this outcome measure.
Secondary
Change From Baseline in Clinical Global Impression - Severity of Illness (CGI-S) Score at 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).
Time frame: Baseline, Week 26
Population: Due to the early termination of study and limited number of participants who completed the double-blind period, the efficacy analyses were not performed and data were not collected for this outcome measure.
Secondary
Change From Baseline in Paediatric Quality of Life Enjoyment and Satisfaction Questionnaire (PQ-LES-Q) Total Score (Items 1 to 14) at Week 26
The PQ-LES-Q is a participant-rated scale designed to assess satisfaction with life. It is an adaptation of the Quality of Life Enjoyment and Satisfaction Questionnaire, which is used to measure quality of life in adults. The PQ-LES-Q consist of 15 items, item 1 to 14 assess the degree of satisfaction experienced by participants in various areas of daily functioning, and item 15 allows participants to summarise 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 to 14 is 14 to 70, with higher scores indicating greater satisfaction.
Time frame: Baseline, Week 26
Population: Due to the early termination of study and limited number of participants who completed the double-blind period, the efficacy analyses were not performed and data were not collected for this outcome measure.
Secondary
Clinical Global Impression - Global Improvement (CGI-I) Score at 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).
Time frame: Week 26
Population: Due to the early termination of study and limited number of participants who completed the double-blind period, the efficacy analyses were not performed and data were not collected for this outcome measure.
Secondary
Plasma Concentration of Vortioxetine
Time frame: From randomization to Week 26 in the double-blind treatment period
Population: Due to early termination of the study, the pharmacokinetic analyses were not performed and the data were not collected.
Secondary
Relapse Rate in the Double-blind Period: Percentage of Participants With Relapse
Relapse was defined as either a total score ≥40 on the CDRS-R with a history of 2 weeks of clinical deterioration, or clinical deterioration as judged by the clinician. The CDRS-R is rated by a clinician following interviews with the child and parent and consists of 17 items out of which 3 items rate nonverbal observations (listless speech, hypoactivity, and depressed affect). Fourteen items are rated on a 7-point scale from 1 to 7, and 3 items (sleep disturbance, appetite disturbance, and listless speech) are scored on a 5-point scale from 1 to 5. A rating of 1 indicates normal functioning and a higher number indicates a greater degree of depression. The total score ranges from 17 (normal) to 113 (severe depression).
Time frame: From randomization to Week 26 in the double-blind treatment period
Population: Due to the early termination of study and limited number of participants who completed the double-blind period, the efficacy analyses were not performed and data were not collected for this outcome measure.