Clinical Trial Results:
A Double-blind, Randomized, Placebo-controlled, Multicentre, Relapse-prevention Study of Vortioxetine in Paediatric Patients Aged 7 to 11 Years With Major Depressive Disorder
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Summary
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EudraCT number |
2010-020493-42 |
Trial protocol |
BG PL LV ES |
Global end of trial date |
28 Apr 2022
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Results information
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Results version number |
v1 |
This version publication date |
04 Oct 2022
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First version publication date |
04 Oct 2022
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Other versions |
v2 |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
13546A
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT05014919 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
H. Lundbeck A/S
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Sponsor organisation address |
Ottiliavej 9, Valby, Denmark, 2500
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Public contact |
LundbeckClinicalTrials@lundbeck.com, H. Lundbeck A/S, +45 36301311, LundbeckClinicalTrials@lundbeck.com
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Scientific contact |
LundbeckClinicalTrials@lundbeck.com, H. Lundbeck A/S, +45 36301311, LundbeckClinicalTrials@lundbeck.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
Yes
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EMA paediatric investigation plan number(s) |
EMEA-000455-PIP02-10 | ||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
28 Apr 2022
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
31 Mar 2022
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Global end of trial reached? |
Yes
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Global end of trial date |
28 Apr 2022
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
The primary objective of the trail was to evaluate the efficacy of vortioxetine in the prevention of relapse of major depressive episodes in paediatric participants with Major Depressive Disorder (MDD).
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Protection of trial subjects |
This study was conducted in compliance with Good Clinical Practice.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
10 Aug 2021
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Colombia: 6
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Country: Number of subjects enrolled |
Mexico: 14
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Country: Number of subjects enrolled |
United States: 5
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Country: Number of subjects enrolled |
Latvia: 1
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Country: Number of subjects enrolled |
Poland: 4
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Country: Number of subjects enrolled |
Russian Federation: 4
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Country: Number of subjects enrolled |
Ukraine: 1
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Worldwide total number of subjects |
35
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EEA total number of subjects |
5
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
29
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Adolescents (12-17 years) |
6
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Adults (18-64 years) |
0
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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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. | ||||||||||||||||||
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Pre-assignment
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Screening 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. | ||||||||||||||||||
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Period 1
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Period 1 title |
Open-Label (12 Weeks)
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Is this the baseline period? |
Yes | ||||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||||
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Arms
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Arm title
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Open-Label Treatment: Vortioxetine | ||||||||||||||||||
Arm description |
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. | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
Vortioxetine
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Coated tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Vortioxetine was administered per dose and schedule specified in the arm description.
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| Notes [1] - 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: Of 5 participants who completed open-label period, only 2 participants entered in the double-blind period. |
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Period 2
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Period 2 title |
Double-Blind (26 Weeks)
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Is this the baseline period? |
No | ||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | ||||||||||||||||||
Roles blinded |
Subject, Investigator, Carer, Assessor | ||||||||||||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Double-Blind Relapse Prevention: Vortioxetine | ||||||||||||||||||
Arm description |
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. | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
Vortioxetine
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Coated tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Vortioxetine was administered per dose and schedule specified in the arm description.
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Arm title
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Double-Blind Relapse Prevention: Placebo | ||||||||||||||||||
Arm description |
Participants received placebo matched to vortioxetine for 26 weeks in the double-blind relapse prevention period. | ||||||||||||||||||
Arm type |
Placebo | ||||||||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Coated tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Placebo matched to vortioxetine was administered per schedule specified in the arm description.
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| Notes [2] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period. Justification: A total of 35 participants enrolled in this study: 33 in the open-label period and 2 in the double-blind period. |
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Baseline characteristics reporting groups
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Reporting group title |
Open-Label Treatment: Vortioxetine
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Reporting group description |
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. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Open-Label Treatment: Vortioxetine
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Reporting group description |
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. | ||
Reporting group title |
Double-Blind Relapse Prevention: Vortioxetine
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Reporting group description |
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. | ||
Reporting group title |
Double-Blind Relapse Prevention: Placebo
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Reporting group description |
Participants received placebo matched to vortioxetine for 26 weeks in the double-blind relapse prevention period. | ||
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End point title |
Time to Relapse in the Double-blind Period [1] | ||||||||||||
End point description |
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). 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 endpoint.
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End point type |
Primary
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End point timeframe |
From randomisation to Week 26 in the double-blind treatment period
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: This endpoint is for double-blind period only. |
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| Notes [2] - The efficacy analyses were not performed and data were not collected for this endpoint. [3] - The efficacy analyses were not performed and data were not collected for this endpoint. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Relapse Rate in the Double-blind Period: Percentage of Participants With Relapse | ||||||||||||
End point description |
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). 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 endpoint.
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End point type |
Secondary
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End point timeframe |
From randomisation to Week 26 in the double-blind treatment period
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| Notes [4] - The efficacy analyses were not performed and data were not collected for this endpoint. [5] - The efficacy analyses were not performed and data were not collected for this endpoint. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Change From Baseline in Children's Depression Rating Scale - Revised Version (CDRS-R) Total Score at Week 26 | ||||||||||||
End point description |
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). 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 endpoint.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 26
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| Notes [6] - The efficacy analyses were not performed and data were not collected for this endpoint. [7] - The efficacy analyses were not performed and data were not collected for this endpoint. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Change From Baseline in Clinical Global Impression - Severity of Illness (CGI-S) Score at Week 26 | ||||||||||||
End point description |
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). 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 endpoint.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 26
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| Notes [8] - The efficacy analyses were not performed and data were not collected for this endpoint. [9] - The efficacy analyses were not performed and data were not collected for this endpoint. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Clinical Global Impression - Global Improvement (CGI-I) Score at Week 26 | ||||||||||||
End point description |
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). 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 endpoint.
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End point type |
Secondary
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End point timeframe |
Week 26
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| Notes [10] - The efficacy analyses were not performed and data were not collected for this endpoint. [11] - The efficacy analyses were not performed and data were not collected for this endpoint. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Change From Baseline in Paediatric Quality of Life Enjoyment and Satisfaction Questionnaire (PQ-LES-Q) Total Score (Items 1 to 14) at Week 26 | ||||||||||||
End point description |
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. 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 endpoint.
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End point type |
Secondary
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End point timeframe |
Baseline, Week 26
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| Notes [12] - The efficacy analyses were not performed and data were not collected for this endpoint. [13] - The efficacy analyses were not performed and data were not collected for this endpoint. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Plasma Concentration of Vortioxetine | ||||||||||||
End point description |
Due to early termination of the study, the pharmacokinetic analyses were not performed and the data were not collected.
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End point type |
Secondary
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End point timeframe |
From randomisation to Week 26 in the double-blind treatment period
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| Notes [14] - Pharmacokinetic analyses were not performed and the data were not collected. [15] - Pharmacokinetic analyses were not performed and the data were not collected. |
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| No statistical analyses for this end point | |||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Baseline (Week 0) up to Week 42
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Adverse event reporting additional description |
All-patients-enrolled (APES) included all participants enrolled to the 12-week open-label, flexible-dose treatment period who took at least 1 dose of study drug. All-patients-randomized set (APRS) included all participants randomized to the 26-week double-blind treatment period.
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
24.0
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Reporting groups
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Reporting group title |
Open-Label Treatment: Vortioxetine
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Reporting group description |
Participants initiated treatment with vortioxetine tablets 5 mg/day orally for the first 2 days and thereafter they received 10 mg/day vortioxetine. Based on the response and dose-limiting 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. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Double-Blind Relapse Prevention: Placebo
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Reporting group description |
Participants received placebo matched to vortioxetine for 26 weeks in the double-blind relapse prevention period. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Double-Blind Relapse Prevention: Vortioxetine
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Reporting group description |
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. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 2% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| The study was terminated based on new efficacy data from another study. The main primary and secondary efficacy objectives were not assessed due to termination of the study and the limited number of participants who completed the double-blind period. | |||
