A Long-term Comparison of Esketamine Nasal Spray Versus Quetiapine Extended Release, Both in Combination With a Selective Serotonin Reuptake Inhibitor/Serotonin-Norepinephrine Reuptake Inhibitor, in Participants With Treatment Resistant Major Depressive Disorder
- Conditions
- Depressive Disorder, Major
- Interventions
- Registration Number
- NCT04338321
- Lead Sponsor
- Janssen-Cilag International NV
- Brief Summary
The primary purpose of this study is to evaluate the efficacy of flexibly dosed esketamine nasal spray compared with quetiapine extended-release (XR), both in combination with a continuing selective serotonin reuptake inhibitor/serotonin-norepinephrine reuptake inhibitor (SSRI/SNRI), in achieving remission in participants who have treatment-resistant major depressive disorder (MDD) with a current moderate to severe depressive episode.
- Detailed Description
A depressive state with classical symptoms such as low (depressive/sad) mood, markedly diminished interest in activities, significant weight loss/gain, insomnia or hypersomnia, psychomotor agitation/retardation, excessive fatigue, inappropriate guilt, diminished concentration, and recurrent thoughts of death, persisting for more than 2 weeks is classified as major depressive disorder (MDD). The mechanism of action of ketamine is distinct from conventional antidepressants (ADs), which target the monoamines (serotonin, norepinephrine, and/or dopamine). Esketamine, the S-enantiomer of ketamine, is approved and widely used for the induction and maintenance of anesthesia via intramuscular or intravenous (IV) administration. There is a significant unmet need to develop novel AD treatments based on the relevant psychophysiological pathways underlying MDD. The goal of any novel treatment would be the rapid and long-lasting relief of depressive symptoms, especially in participants with treatment-resistant depression (TRD), who lack a sufficient response to the currently available treatment strategies. The study consists of a Screening Phase (up to 14 days), an Acute Phase (8 Weeks), a Maintenance Phase (24 Weeks) and a Safety Follow-up Phase (2 Weeks). Safety assessment includes adverse event, serious adverse events, physical examination, vital signs, electrocardiogram, clinical safety laboratory assessments, suicidal risk monitoring. The total duration of the study is approximately 36 Weeks for all participants.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 676
- At screening, each participant must meet Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) diagnostic criteria for single-episode major depressive disorder (MDD) or recurrent MDD, without psychotic features, based on clinical assessment and confirmed by the Mini International Neuropsychiatric Interview (MINI)
- At screening and baseline, each participant must have an Inventory of Depressive Symptomatology - Clinician-rated, 30 item (IDS-C30) total score of greater than or equal to (>=) 34
- Must be on a current antidepressive treatment that includes an selective serotonin reuptake inhibitor (SSRI)/ serotonin-norepinephrine reuptake inhibitor (SNRI) at screening that resulted in nonresponse (less than 25% improvement of symptoms) after having been given at an adequate dosage (based on antidepressive dosages from SmPC [or local equivalent, if applicable]) for an adequate duration of at least 6 weeks and having been uptitrated to the maximum tolerated dose; however, at screening the participant must show signs of minimal clinical improvement to be eligible for the study. Clinical improvement of a participant on their current AD treatment will be retrospectively evaluated in a qualified psychiatric interview performed by an experienced clinician. At baseline (Day 1) prior to randomization, the investigator will evaluate any changes in the participant's signs/symptoms of depression since the screening assessment and confirm that the inclusion criteria for the current AD treatment are still met (that is nonresponse and minimal clinical improvement)
- The current antidepressive treatment, was immediately preceded by nonresponse to at least 1 but not more than 5 different, consecutive treatments (all within the current moderate to severe antidepressive episode) with anti-depressants (ADs) taken at an adequate dosage for an adequate duration of at least 6 weeks and must be documented
- Must have been treated with at least 2 different antidepressive substance classes among the treatments taken at an adequate dosage for an adequate duration of at least 6 weeks resulting in nonresponse in the current moderate to severe depressive episode (including the current treatment with an selective serotonin reuptake inhibitor/serotonin-norepinephrine reuptake inhibitor [SSRI/SNRI])
- Must be on a single oral SSRI/SNRI on Day 1 prior to randomization
- Received treatment with esketamine or ketamine in the current moderate to severe depressive episode
- Received treatment with quetiapine extended- or immediate-release in the current moderate to severe depressive episode of a dose higher than 50 milligram per day (mg/day)
- Had depressive symptoms in the current moderate to severe depressive episode that previously did not respond to an adequate course of treatment with electroconvulsive therapy (ECT), defined as at least 7 treatments with unilateral/bilateral ECT
- Has no signs of clinical improvement at all or with a significant improvement on their current AD treatment that includes an SSRI/SNRI as determined at screening by an experienced clinician during the qualified psychiatric interview
- Received vagal nerve stimulation or has received deep brain stimulation in the current episode of depression
- has a current or prior DSM-5 diagnosis of a psychotic disorder or MDD with psychotic features, bipolar or related disorders (confirmed by the Mini International Neuropsychiatric Interview [MINI]), obsessive compulsive disorder (current only), intellectual disability (DSM-5 diagnostic codes 317, 318.0, 318.1, 318.2, 315.8, and 319), autism spectrum disorder, borderline personality disorder, or antisocial personality disorder, histrionic personality disorder, or narcissistic personality disorder
- age at onset of first episode of MDD was more than or equal to (>=) 55 years
- has homicidal ideation or intent, per the investigator's clinical judgment; or has suicidal ideation with some intent to act within 1 month prior to screening, per the investigator's clinical judgment; or based on the Columbia-Suicide Severity Rating Scale (C-SSRS), corresponding to a response of "Yes" on Item 4 (active suicidal ideation with some intent to act, without specific plan) or Item 5 (active suicidal ideation with specific plan and intent) for suicidal ideation, or a history of suicidal behavior within the past year prior to screening. Participants reporting suicidal ideation with intent to act or suicidal behavior prior to the start of the acute phase should also be excluded
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Comparator Arm Quetiapine XR 150 mg Participants will continue to take their current SSRI/SNRI augmented with quetiapine extended release (XR) as per the Summary of Product Characteristics (SmPC) (or local equivalent, if applicable). In adult participants aged 18 to 64 years, the initial dose is 50 mg/day on Days 1-2, 150 mg/day on Days 3-4 \[lowest effective dose\]; a further dose increase to 300 mg/day on Day 5 and onward will be based on individual participant evaluation. In elderly participants aged 65 to 74 years, the initial dose is 50 mg/day on Days 1-3, 100 mg/day on Days 4-7, and 150 mg/day on Day 8; a further dose increase to 300 mg/day will be based on individual participant evaluation no earlier than Day 22. Esketamine Arm Esketamine 84 mg Participants will receive treatment with esketamine nasal spray (28 milligram \[mg\] \[initial dose for elderly participants 65 to 74 years of age and adults of Japanese ancestry; may be used throughout the study in these populations; may be uptitrated in 28 mg increments\], 56 mg \[initial dose for adult participants aged 18 to 64 years and may be used for all age groups throughout the study\], or 84 mg \[maximum dose esketamine nasal spray may be uptitrated to\]) twice-weekly with a flexible dose regimen from Day 1 until Week 4, once weekly from Week 5 to Week 8 and once-weekly or once every 2 weeks from Week 9 to Week 32 in combination with continuing serotonin-norepinephrine reuptake inhibitor/selective serotonin reuptake inhibitor (SSRI/SNRI). Esketamine Arm Esketamine 28 mg Participants will receive treatment with esketamine nasal spray (28 milligram \[mg\] \[initial dose for elderly participants 65 to 74 years of age and adults of Japanese ancestry; may be used throughout the study in these populations; may be uptitrated in 28 mg increments\], 56 mg \[initial dose for adult participants aged 18 to 64 years and may be used for all age groups throughout the study\], or 84 mg \[maximum dose esketamine nasal spray may be uptitrated to\]) twice-weekly with a flexible dose regimen from Day 1 until Week 4, once weekly from Week 5 to Week 8 and once-weekly or once every 2 weeks from Week 9 to Week 32 in combination with continuing serotonin-norepinephrine reuptake inhibitor/selective serotonin reuptake inhibitor (SSRI/SNRI). Esketamine Arm Esketamine 56 mg Participants will receive treatment with esketamine nasal spray (28 milligram \[mg\] \[initial dose for elderly participants 65 to 74 years of age and adults of Japanese ancestry; may be used throughout the study in these populations; may be uptitrated in 28 mg increments\], 56 mg \[initial dose for adult participants aged 18 to 64 years and may be used for all age groups throughout the study\], or 84 mg \[maximum dose esketamine nasal spray may be uptitrated to\]) twice-weekly with a flexible dose regimen from Day 1 until Week 4, once weekly from Week 5 to Week 8 and once-weekly or once every 2 weeks from Week 9 to Week 32 in combination with continuing serotonin-norepinephrine reuptake inhibitor/selective serotonin reuptake inhibitor (SSRI/SNRI). Comparator Arm Quetiapine XR 50 mg Participants will continue to take their current SSRI/SNRI augmented with quetiapine extended release (XR) as per the Summary of Product Characteristics (SmPC) (or local equivalent, if applicable). In adult participants aged 18 to 64 years, the initial dose is 50 mg/day on Days 1-2, 150 mg/day on Days 3-4 \[lowest effective dose\]; a further dose increase to 300 mg/day on Day 5 and onward will be based on individual participant evaluation. In elderly participants aged 65 to 74 years, the initial dose is 50 mg/day on Days 1-3, 100 mg/day on Days 4-7, and 150 mg/day on Day 8; a further dose increase to 300 mg/day will be based on individual participant evaluation no earlier than Day 22. Comparator Arm Quetiapine XR 100 mg Participants will continue to take their current SSRI/SNRI augmented with quetiapine extended release (XR) as per the Summary of Product Characteristics (SmPC) (or local equivalent, if applicable). In adult participants aged 18 to 64 years, the initial dose is 50 mg/day on Days 1-2, 150 mg/day on Days 3-4 \[lowest effective dose\]; a further dose increase to 300 mg/day on Day 5 and onward will be based on individual participant evaluation. In elderly participants aged 65 to 74 years, the initial dose is 50 mg/day on Days 1-3, 100 mg/day on Days 4-7, and 150 mg/day on Day 8; a further dose increase to 300 mg/day will be based on individual participant evaluation no earlier than Day 22. Esketamine Arm SSRI/SNRI Participants will receive treatment with esketamine nasal spray (28 milligram \[mg\] \[initial dose for elderly participants 65 to 74 years of age and adults of Japanese ancestry; may be used throughout the study in these populations; may be uptitrated in 28 mg increments\], 56 mg \[initial dose for adult participants aged 18 to 64 years and may be used for all age groups throughout the study\], or 84 mg \[maximum dose esketamine nasal spray may be uptitrated to\]) twice-weekly with a flexible dose regimen from Day 1 until Week 4, once weekly from Week 5 to Week 8 and once-weekly or once every 2 weeks from Week 9 to Week 32 in combination with continuing serotonin-norepinephrine reuptake inhibitor/selective serotonin reuptake inhibitor (SSRI/SNRI). Comparator Arm SSRI/SNRI Participants will continue to take their current SSRI/SNRI augmented with quetiapine extended release (XR) as per the Summary of Product Characteristics (SmPC) (or local equivalent, if applicable). In adult participants aged 18 to 64 years, the initial dose is 50 mg/day on Days 1-2, 150 mg/day on Days 3-4 \[lowest effective dose\]; a further dose increase to 300 mg/day on Day 5 and onward will be based on individual participant evaluation. In elderly participants aged 65 to 74 years, the initial dose is 50 mg/day on Days 1-3, 100 mg/day on Days 4-7, and 150 mg/day on Day 8; a further dose increase to 300 mg/day will be based on individual participant evaluation no earlier than Day 22.
- Primary Outcome Measures
Name Time Method Percentage of Participants With Remission as Assessed by the Montgomery-Asberg Depression Rating Scale (MADRS) Score at Week 8 Week 8 Percentage of participants with remission as assessed by the MADRS at Week 8 was reported. The MADRS is a clinician-rated scale designed to measure depression severity and to detect changes due to antidepressant treatment. The scale consists of 10 items, each of which is scored from 0 (item is not present or is normal) to 6 (severe or continuous presence of the symptoms), for a total possible score of 60. Higher scores represent a more severe condition. The MADRS evaluates apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic thoughts, and suicidal thoughts. A participant was defined as being in remission if the MADRS total score was less than or equal to (\<=)10 and no treatment or study discontinuation before Week 8.
- Secondary Outcome Measures
Name Time Method Percentage of Participants With Both Remission at Week 8 and Relapse-free Until Week 32 Week 32 Percentage of participants with both remission at Week 8 and relapse-free until Week 32 were reported. A participant was defined as being in remission if the MADRS total score was \<= 10 and no treatment or study discontinuation before Week 8. A relapse was defined by any of following: a) Worsening of depressive symptoms as indicated by MADRS total score greater than or equal to (\>=) 22 confirmed by 1 additional assessment of MADRS total score \>= 22 within the next 5 to 15 days. The date of the second MADRS assessment was used for the date of relapse; b) Any psychiatric hospitalization for: worsening of depression, suicide prevention or suicide attempt, the start date of hospitalization was the date of relapse; c) Suicide attempt, completed suicide, or any other clinically relevant event determined by investigator's judgment to be indicative of a relapse of depressive illness, but without hospitalized. The onset of the event was used for the date of relapse.
Change From Baseline in Clinician-rated Overall MADRS Score Baseline, Weeks 1, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32 Change from baseline in clinician-rated overall MADRS score was reported. The MADRS is a clinician-rated scale designed to measure depression severity and to detect changes due to antidepressant treatment. The scale consists of 10 items, each of which is scored from 0 (item is not present or is normal) to 6 (severe or continuous presence of the symptoms), summed up for a total possible score range of 0 to 60. Higher scores represent a more severe condition. The MADRS evaluates apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic thoughts, and suicidal thoughts.
Change From Baseline in Participant-reported Functional Impairment and Associated Disability as Assessed by SDS Total Score at LOCF Baseline, LOCF at Weeks 4, 8, 12, 16, 20, 24, 28, 32 Change from baseline in participant-reported functional impairment and associated disability as assessed by SDS total score at LOCF was reported. The SDS is a validated PRO measure consisting of a 5-item questionnaire for assessment of functional impairment and associated disability. The first 3 items assess disruption of (1) work/school, (2) social life, and (3) family life/home responsibilities using a rating scale from 0 to 10. It also has 1 item assessing days lost from school or work and 1 item assessing days of underproductivity. The scores for the first 3 items are summed to create a total score of 0 to 30, where higher score indicates greater impairment. Scores \<=2 for each item and \<= 6 for the total score are considered functional remission. LOCF is defined as the participants who had a missing value or who stopped treatment at a specific time point had their last non-missing value carried forward.
Change From Baseline in Participant-reported Depressive Symptoms as Assessed by Patient Health Questionnaire (PHQ) 9-item Total Score Baseline, Weeks 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32 Change from baseline in participant-reported depressive symptoms as assessed by PHQ 9-item total score was reported. The PHQ-9 is a validated 9-item, patient-reported outcome (PRO) measure to assess depressive symptoms. Each item is rated on a 4-point scale (0=not at all, 1=several days, 2=more than half the days, and 3=nearly every day). The participant's item responses are summed to provide a total score (range of 0 to 27), with higher scores indicating greater severity of depressive symptoms. The severity of the PHQ-9 is categorized as follows: None-minimal (0-4), Mild (5-9), Moderate (10-14), Moderately Severe (15-19) and Severe (20-27).
Change From Baseline in Participant-reported Depressive Symptoms as Assessed by PHQ 9-item Total Score at LOCF Baseline, LOCF at Weeks 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32 Change from baseline in participant-reported depressive symptoms as assessed by PHQ 9-item total score at LOCF was reported. The PHQ-9 is a validated 9-item, PRO measure to assess depressive symptoms. Each item is rated on a 4-point scale (0=not at all, 1=several days, 2=more than half the days, and 3=nearly every day). The participant's item responses are summed to provide a total score (range of 0 to 27), with higher scores indicating greater severity of depressive symptoms. The severity of the PHQ-9 is categorized as follows: None-minimal (0-4), Mild (5-9), Moderate (10-14), Moderately Severe (15-19) and Severe (20-27). LOCF is defined as participants who had a missing value or who stopped treatment at a specific time point had their last non-missing value carried forward.
Change From Baseline in Clinician-rated Overall MADRS Score at Last Observation Carried Forward (LOCF) Baseline, LOCF at Weeks 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32 Change from baseline in clinician-rated overall MADRS score at LOCF was reported. The MADRS is a clinician-rated scale designed to measure depression severity and to detect changes due to antidepressant treatment. The scale consists of 10 items, each of which is scored from 0 (item is not present or is normal) to 6 (severe or continuous presence of the symptoms), summed up for a total possible score range of 0 to 60. Higher scores represent a more severe condition. The MADRS evaluates apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic thoughts, and suicidal thoughts. LOCF is defined as the participants who had a missing value or who stopped treatment at a specific time point had their last non-missing value carried forward.
Change From Baseline in Clinician-rated Overall Severity of Depressive Illness as Assessed by Clinical Global Impression - Severity (CGI-S) Scale Score Baseline, Weeks 1, 2, 3, 4, 8, 12, 16, 20, 24, 28, 32 Change from baseline in clinician-rated overall severity of depressive illness as assessed by CGI-S scale score was reported. The CGI-S provides an overall clinician-determined summary measure of the severity of the participant's illness that takes into account all available information, including knowledge of the participant's history, psychosocial circumstances, symptoms, behavior, and the impact of the symptoms on the participant's ability to function. The CGI-S evaluates the severity of psychopathology on a scale of 1 to 7. Considering total clinical experience, a participant is assessed on severity of mental illness at the time of rating according to: 1 = normal (not at all ill); 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; 7 = among the most extremely ill participants. Negative change in score indicates improvement.
Change From Baseline in Clinician-rated Overall Severity of Depressive Illness as Assessed by CGI-S Scale Score at LOCF Baseline, LOCF at Weeks 2, 3, 4, 8, 12, 16, 20, 24, 28, 32 Change from Baseline in clinician-rated overall severity of depressive illness as assessed by CGI-S scale score at LOCF was reported. The CGI-S provides an overall clinician-determined summary measure of the severity of the participant's illness that takes into account all available information, including knowledge of the participant's history, psychosocial circumstances, symptoms, behavior, and the impact of the symptoms on the participant's ability to function. The CGI-S evaluates the severity of psychopathology on a scale of 1 to 7. A participant is assessed on severity of mental illness at the time of rating according to: 1 = normal (not at all ill); 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; 7 = among the most extremely ill participants. LOCF is defined as the participants who had a missing value or who stopped treatment at a specific time point had their last non-missing value carried forward.
Clinician-rated Overall Severity of Depressive Illness as Assessed by Clinical Global Impression - Change (CGI-C) Scale Score Baseline, Weeks 1, 2, 3, 4, 8, 12, 16, 20, 24, 28, 32 Clinician-rated overall severity of depressive illness as assessed by CGI-C scale score was reported. The CGI-C evaluates the total improvement whether or not entirely due to drug treatment on a scale of 1 to 7. Compared to the condition at baseline, a participant is assessed on how much he/she has changed, according to: 1 = very much improved; 2 = much improved; 3 = minimally improved; 4 = no change; 5 = minimally worse; 6 = much worse; 7 = very much worse. Higher scores indicate more severity.
Number of Participants With Clinician-rated Overall Severity of Depressive Illness as Assessed by CGI-C Scale Score at LOCF Baseline, LOCF at Weeks 2, 3, 4, 8, 12, 16, 20, 24, 28, 32 Number of participants with clinician-rated overall severity of depressive illness as assessed by CGI-C scale score at LOCF was reported. The CGI-C evaluates the total improvement whether or not entirely due to drug treatment on a scale of 1 to 7. Compared to the condition at baseline, a participant is assessed on how much he/she has changed, according to: 1 = very much improved; 2 = much improved; 3 = minimally improved; 4 = no change; 5 = minimally worse; 6 = much worse; 7 = very much worse. Higher scores indicate more severity. LOCF is defined as the participants who had a missing value or who stopped treatment at a specific time point had their last non-missing value carried forward.
Change From Baseline in Participant-reported Functional Impairment and Associated Disability as Assessed by Sheehan Disability Scale (SDS) Total Score Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32 Change from baseline in participant-reported functional impairment and associated disability as assessed by SDS total score was reported. The SDS is a validated PRO measure consisting of a 5-item questionnaire that has been widely used and accepted for assessment of functional impairment and associated disability. The first 3 items assess disruption of (1) work/school, (2) social life, and (3) family life/home responsibilities using a rating scale from 0 to 10. It also has 1 item assessing days lost from school or work and 1 item assessing days of underproductivity. The scores for the first 3 items are summed to create a total score of 0 to 30, where higher score indicates greater impairment. Scores \<=2 for each item and \<= 6 for the total score are considered functional remission.
Change From Baseline in Participant-reported Health-related Quality of Life (HRQoL) and Health Status as Assessed by 36-item Short-Form Health Survey (SF-36) Scale Score Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32 Change from baseline in participant-reported HRQoL and health status as assessed by SF-36 scale score was reported. The SF-36 consists of 8 subscales (physical function, role limitations due to physical problems, pain, general health perception, vitality, social function, role limitations due to emotional problems, and mental health). Participants self-report on items in a subscale that have between 2-6 choices per item using likert-type responses (for example: none of the time, some of the time, etc.). Summations of item scores of the same subscale give the subscale scores, which are transformed into a range from 0 to 100; 0= worst HRQoL, 100=best HRQoL. Higher scores indicate better health status.
Change From Baseline in Participant-reported Quality of Life as Assessed by QLDS Total Score at LOCF Baseline, LOCF at Weeks 4, 8, 12, 16, 20, 24, 28, 32 Change from baseline in participant-reported quality of life as assessed by QLDS total score at LOCF was reported. The QLDS is a disease-specific validated PRO measure which assesses the impact that depression has on a participant's quality of life. It is a 34-item self-rated questionnaire which consists of dichotomous response questions, with the response being either True/Not True. Each statement on the QLDS is given a score of "1" or "0". A score of "1" is indicative of adverse quality of life. All item scores are summed to give a total score that ranges from 0 (good quality of life) to 34 (very poor quality of life). A higher score indicates a more severe condition. LOCF is defined as the participants who had a missing value or who stopped treatment at a specific time point had their last non-missing value carried forward.
Change From Baseline in Participant-reported Health-related Quality of Life as Assessed by EuroQol-5 Dimension-5 Level (EQ-5D-5L) Score: Health Status Index Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32 Change from baseline in participant-reported health-related quality of Life as assessed by EQ-5D-5L score: health status index was reported. The EQ-5D-5L is a standardized 2-part instrument used to measure health outcomes, primarily designed for self-completion by respondents. It consists of the EQ-5D-5L descriptive system and the EQ Visual Analogue Scale (EQ-VAS). The EQ-5D-5L descriptive system comprises the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each of the 5 dimensions is divided into 5 levels of perceived problems (level 1 = no problem, level 2 = slight problems, level 3 = moderate problems, level 4 = severe problems, level 5 = extreme problems). The participant selects an answer for each of the 5 dimensions considering the response that best matches his or her health "today." Responses were used to generate health status index which ranges from 0 (dead) and 1 (full health), a lower score indicates worse health.
Change From Baseline in Participant-reported Health-related Quality of Life Group, as Assessed by EQ-5D-5L Score: Health Status Index at LOCF Baseline, LOCF at Weeks 4, 8, 12, 16, 20, 24, 28, 32 Change from baseline in participant-reported health-related quality of Life as assessed by EQ-5D-5L score: health status index at LOCF was reported. The EQ-5D-5L is a standardized 2-part instrument used to measure health outcomes, primarily designed for self-completion by respondents. It consists of the EQ-5D-5L descriptive system and the EQ-VAS. The EQ-5D-5L descriptive system comprises of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each of the 5 dimensions is divided into 5 levels of perceived problems (level 1 = no problem, level 2 = slight problems, level 3 = moderate problems, level 4 = severe problems, level 5 = extreme problems). The participant selects an answer for each of the 5 dimensions considering the response that best matches his or her health "today." LOCF is defined as the participants who had a missing value or who stopped treatment at a specific time point had their last non-missing value carried forward.
Change From Baseline in Participant-reported Health Status as Assessed by EQ-5D-5L Score: VAS at LOCF Baseline, LOCF at Weeks 4, 8, 12, 16, 20, 24, 28, 32 Change from baseline in participant-reported health status as assessed by EQ-5D-5L score: VAS at LOCF was reported. The EQ-5D-5L is a standardized 2-part instrument for use as a measure of health outcome, primarily designed for self-completion by respondents. It essentially consists of the EQ-5D-5L descriptive system and the EQ-VAS. EQ-VAS self-rating records the respondent's own assessment of his/her overall health status at time of completion, on a scale of 0 (worst health you can imagine) to 100 (best health you can imagine). Positive change in score indicates improvement. LOCF is defined as the participants who had a missing value or who stopped treatment at a specific time point had their last non-missing value carried forward.
Change From Baseline in Participant-reported Quality of Life as Assessed by Quality of Life in Depression Scale (QLDS) Total Score Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32 Change from baseline in participant-reported quality of life as assessed by QLDS total score was reported. The QLDS is a disease-specific validated PRO measure which assesses the impact that depression has on a participant's quality of life. It is a 34-item self-rated questionnaire which consists of dichotomous response questions, with the response being either True/Not True. Each statement on the QLDS is given a score of "1" or "0". A score of "1" is indicative of adverse quality of life. All item scores are summed to give a total score that ranges from 0 (good quality of life) to 34 (very poor quality of life). A higher score indicates a more severe condition.
Change From Baseline in Participant-reported HRQoL and Health Status as Assessed by SF-36 Scale Score at LOCF Baseline, LOCF at Weeks 8, 12, 16, 20, 24, 28, 32 Change from baseline in participant-reported HRQoL and health status as assessed by SF-36 domain scores at LOCF was reported. The SF-36 consists of 8 subscales (physical function, role limitations due to physical problems, pain, general health perception, vitality, social function, role limitations due to emotional problems, and mental health). Participants self-report on items in a subscale that have between 2-6 choices per item using likert-type responses (for example: none of the time, some of the time, etc.). Summations of item scores of the same subscale give the subscale scores, which are transformed into a range from 0 to 100; 0= worst HRQoL, 100=best HRQoL. Higher scores indicate better health status. LOCF is defined as participants who had a missing value or who stopped treatment at a specific time point had their last non-missing value carried forward.
Change From Baseline in Participant-reported Work Productivity as Assessed by WPAI: Depression Questionnaire at LOCF Baseline, LOCF at Weeks 4, 8, 12, 16, 20, 24, 28, 32 Change from baseline in participant-reported work productivity as assessed by WPAI: depression questionnaire at LOCF was reported. The WPAI-D questionnaire is a validated short instrument that assesses impairment in work and other regular activities over the past 7 days. The WPAI yields four types of scores: (a) Absenteeism (work time missed); (b) Presenteeism (impairment at work / reduced on-the-job effectiveness); (c) Work productivity loss (overall work impairment / absenteeism plus presenteeism); (d) Activity Impairment. The first three scores were derived only for respondents who were working (should be missing for non-working), but the last score was applicable for all respondents. Each score ranges from 0 to 100 with higher scores indicating greater impairment and less productivity. LOCF is defined as the participants who had a missing value or who stopped treatment at a specific time point had their last non-missing value carried forward.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) Up to Week 35 An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/ biological agent under study. TEAEs were those events if they started after administration of the first dose until 14 days after the last dose of study medication for other TEAEs except serious; and first dose until 30 days after the last dose of study medication for serious TEAEs.
Number of Participants With Suicidal Ideation or Behavior as Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) Score Weeks 1, 2, 3, 4, 8, 12, 16, 20, 24, 28, 32 Number of participants with suicidal ideation or behavior as assessed by C-SSRS score was reported. The C-SSRS is an assessment tool that evaluates suicidal ideation and behavior. Suicidal ideation consists of 5 items: wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with any methods (not plan) without intention to act, active suicidal ideation with some intent to act without specific plan, and active suicidal ideation with specific plan and intent. Suicidal behavior consists of 5 items: preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt (non-fatal), and completed suicide. The maximum score (from the 10 categories) assigned for each participant was summarized into one of three broad categories: No suicidal ideation or behavior (0), Suicidal ideation (1 - 5), Suicidal behavior (6 - 10). Total score ranges from 1 to 10. Higher scores indicate more severe suicidal ideation and behavior.
Change From Baseline in Participant-reported Health Status as Assessed by EQ-5D-5L Score: VAS Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32 Change from baseline in participant-reported health status as assessed by EQ-5D-5L Score: VAS was reported. The EQ-5D-5L is a standardized 2-part instrument for use as a measure of health outcome, primarily designed for self-completion by respondents. It essentially consists of the EQ-5D-5L descriptive system and the EQ-VAS. EQ-VAS self-rating records the respondent's own assessment of his/her overall health status at time of completion, on a scale of 0 (worst health you can imagine) to 100 (best health you can imagine). Positive change in score indicates improvement.
Change From Baseline in Participant-reported Work Productivity as Assessed by Work Productivity and Activity Impairment (WPAI): Depression Questionnaire Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32 Change from baseline in participant-reported work productivity as assessed by WPAI: depression questionnaire was reported. The WPAI-D questionnaire is a validated short instrument that assesses impairment in work and other regular activities over the past 7 days. The WPAI yields four types of scores: (a) Absenteeism (work time missed); (b) Presenteeism (impairment at work / reduced on-the-job effectiveness); (c) Work productivity loss (overall work impairment / absenteeism plus presenteeism); (d) Activity Impairment. The first three scores were derived only for respondents who were working (should be missing for non-working), but the last score was applicable for all respondents. Each score ranges from 0 to 100 with higher scores indicating greater impairment and less productivity.
Number of Participants With TEAEs of Special Interest Up to Week 35 Number of participants with TEAEs of special interest were reported. It included significant TEAEs that were judged to be of special interest because of clinical importance, known or suspected class effects, or based on nonclinical signals. Events such as sedation, depersonalization/derealization disorder, depression suicidal, aggression, allergic cystitis, cholestasis and jaundice of hepatic origin, and many more were considered as TEAEs of special interest.
Trial Locations
- Locations (168)
Ruschel Medicina e Pesquisa Clínica Ltda
🇧🇷Rio de Janeiro, Brazil
C J S Carvalho & Carvalho LTDA (Viver - Centro De Desospitalizacao Humana)
🇧🇷Sao Paulo, Brazil
BR Trials
🇧🇷Sao Paulo, Brazil
State Psychiatric Hospital Kardzhali
🇧🇬Kardzhali, Bulgaria
UMHAT 'Dr. Georgi Stranski', EAD
🇧🇬Pleven, Bulgaria
Mental Health Center - Plovdiv
🇧🇬Plovdiv, Bulgaria
Mental Health Center - Rousse
🇧🇬Rousse, Bulgaria
Multiprofile Hospital for Active Treatment in Neurology and Psychiatry Sveti Naum
🇧🇬Sofia, Bulgaria
MHC - Sofia, EOOD
🇧🇬Sofia, Bulgaria
Centre for Mental Health Prof.N.Shipkovenski EOOD
🇧🇬Sofia, Bulgaria
University Multiprofile Hospital for Active Treatment - UMHAT Alexandrovska EAD
🇧🇬Sofia, Bulgaria
Psychiatricka ambulance Saint Anne s.r.o.
🇨🇿Brno, Czechia
Psychiatricka ambulance, MUDr. Marta Holanova
🇨🇿Brno, Czechia
NeuropsychiatrieHK, s.r.o.
🇨🇿Hradec Kralove-Vekose, Czechia
A Shine S R O
🇨🇿Plzen, Czechia
Institut Neuropsychiatricke pece
🇨🇿Prague, Czechia
Clintrial s r o
🇨🇿Praha 10, Czechia
AD71 s.r.o.
🇨🇿Praha 10, Czechia
Medical Services Prague S R O
🇨🇿Praha 6, Czechia
Aalborg University Hospital
🇩🇰Aalborg, Denmark
Psykiatrien i Region Syddanmark
🇩🇰Esbjerg N, Denmark
Mederon LTD at ARTES
🇫🇮Helsinki, Finland
Psykiatrinen Palvelukeskus Solvum Oy
🇫🇮Helsinki, Finland
Savon Psykiatripalvelu
🇫🇮Kuopio, Finland
Universitaetsklinikum der RWTH Aachen
🇩🇪Aachen, Germany
Rheinhessen Fachklinik Alzey
🇩🇪Alzey, Germany
Emovis GmbH
🇩🇪Berlin, Germany
Charite Campus Benjamin Franklin
🇩🇪Berlin, Germany
Medizinisches Versorgungszentrum LiO GmbH
🇩🇪Berlin, Germany
Alexander Schulze - Germany
🇩🇪Berlin, Germany
Praxis Dr. med. Kirsten Hahn
🇩🇪Berlin, Germany
Vivantes Klinikum Spandau
🇩🇪Berlin, Germany
Universitatsklinikum Bonn
🇩🇪Bonn, Germany
Klinikum Chemnitz gGmbH
🇩🇪Chemnitz, Germany
Carl-Thiem-Klinikum Cottbus gGmbH
🇩🇪Cottbus, Germany
Klinikum Dortmund gGmbH
🇩🇪Dortmund, Germany
Universitatsklinikum Carl Gustav Carcus Dresden
🇩🇪Dresden, Germany
Universitatsklinikum Frankfurt
🇩🇪Frankfurt Am Main, Germany
Universitätsklinikum Freiburg - Abteilung für Psychiatrie u. Psychotherapie mit Poliklinik
🇩🇪Freiburg, Germany
SRH Waldklinikum Gera GmbH
🇩🇪Gera, Germany
Georg August Universitat Universitatsmedizin Gottingen
🇩🇪Gottingen, Germany
Evangelisches Krankenhaus Bethanien gGmbH
🇩🇪Greifswald, Germany
Universitaetsklinik Hamburg-Eppendorf
🇩🇪Hamburg, Germany
Klinische Forschung Hamburg
🇩🇪Hamburg, Germany
Klinische Forschung Hannover-Mitte GmbH
🇩🇪Hannover, Germany
Medizinische Hochschule Hannover
🇩🇪Hannover, Germany
Universität Heidelberg
🇩🇪Heidelberg, Germany
Oberhavel Kliniken GmbH
🇩🇪Hennigsdorf, Germany
Universitätsklinikum des Saarlandes
🇩🇪Homburg, Germany
Universitatsklinikum Jena
🇩🇪Jena, Germany
Panakeia - Arzneimittelforschung GmbH
🇩🇪Leipzig, Germany
Universitaetsklinikum Magdeburg A.oe.R
🇩🇪Magdeburg, Germany
Universitatsmedizin der Johannes Gutenberg Universitat Mainz
🇩🇪Mainz, Germany
Pharmakologisches Studienzentrum Chemnitz GmbH
🇩🇪Mittweida, Germany
Universitatsklinikum Munster
🇩🇪Munster, Germany
Ruppiner Kliniken
🇩🇪Neuruppin, Germany
Praxis Prof. Steinwachs
🇩🇪Nurnberg, Germany
Johanniter Krankenhaus Oberhausen
🇩🇪Oberhausen, Germany
Danuvius Klinik Pfaffenhofen Fachklinik für Psychiatrie, Psychotherapie und Psychosomatik
🇩🇪Pfaffenhofen, Germany
Uls Loures Odivelas - Hosp. Loures
🇵🇹Loures, Portugal
Cape Town Clinical Research Centre
🇿🇦Cape Town, South Africa
Flexivest 14 Research
🇿🇦Cape Town, South Africa
Gert Bosch Pretoria South Africa
🇿🇦Garsfontein, South Africa
Psykiatriska kliniken
🇸🇪Lulea, Sweden
Affecta Pskyiatrimottagning
🇸🇪Halmstad, Sweden
ProbarE i Lund AB
🇸🇪Lund, Sweden
ONE LIFETIME Lakarmottagning
🇸🇪Skovde, Sweden
ProbarE i Stockholm AB
🇸🇪Stockholm, Sweden
Changhua Christian Hospital
🇨🇳ChangHua, Taiwan
Hualien Tzu Chi Hospital
🇨🇳Hualien, Taiwan
Kai-Syuan Psychiatric Hospital
🇨🇳Kaohsiung, Taiwan
Chang Gung Memorial Hospital
🇨🇳Taoyuan, Taiwan
National Cheng Kung University Hospital
🇨🇳Tainan, Taiwan
Taipei Medical University
🇨🇳Taipei City, Taiwan
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
Mackay Memorial Hospital
🇨🇳Taipei, Taiwan
Taipei Veterans General Hospital
🇨🇳Taipei, Taiwan
Hacettepe University Medical Faculty
🇹🇷Ankara, Turkey
Bursa Yuksek Ihtisas Training and Research Hospital
🇹🇷Bursa, Turkey
Uludag University Medical Faculty
🇹🇷Bursa, Turkey
Bakirkoy Mental Health Training and Research Hospital
🇹🇷Istanbul, Turkey
Erenkoy Mental Health Hospital
🇹🇷Istanbul, Turkey
Uskudar University Neuropsychiatry Hospital
🇹🇷Istanbul, Turkey
Ege Universitesi Tip Fakultesi
🇹🇷Izmir, Turkey
Selcuk University Medical Faculty
🇹🇷Konya, Turkey
Liv Hospital
🇹🇷Samsun, Turkey
Namik Kemal University
🇹🇷Tekirdag, Turkey
American Center for Psychiatry and Neurology
🇦🇪Abu Dhabi, United Arab Emirates
FunDaMos
🇦🇷Ciudad Autonoma de Buenos Aires, Argentina
Fundacion para el Estudio y Tratamiento de las Enfermedades Mentales
🇦🇷Ciudad Autónoma De Buenos Aires, Argentina
CEN Consultorios Especializados en Neurociencias
🇦🇷Cordoba, Argentina
Fundacion Lennox
🇦🇷Cordoba, Argentina
Instituto Medico DAMIC
🇦🇷Cordoba, Argentina
Sanatorio Prof Leon S Morra S A
🇦🇷Cordoba, Argentina
Instituto de Neurociencias San Agustin
🇦🇷La Plata, Argentina
C I A P Centro de investigacion y Asistencia en Psiquiatria
🇦🇷Rosario, Argentina
Medical University Graz
🇦🇹Graz, Austria
Schmitz and Schmitz
🇦🇹Vienna, Austria
Medical University Vienna MUV
🇦🇹Vienna, Austria
Anima
🇧🇪Alken, Belgium
Pz Duffel
🇧🇪Duffel, Belgium
Clinique Psychiatrique des Frères Alexiens
🇧🇪Henri Chapelle, Belgium
Sint-Franciskusziekenhuis
🇧🇪Heusden-Zolder, Belgium
ARIADNE
🇧🇪Lede, Belgium
CHU de Liege
🇧🇪Liege, Belgium
CPN - Centro de Pesquisa em Neurociências Ltda
🇧🇷Belo Horizonte, Brazil
Trial Tech Tecnologia em Pesquisas com Medicamentos
🇧🇷Curitiba, Brazil
Somni Bene GmbH
🇩🇪Schwerin, Germany
Klinische Forschung Schwerin GmbH
🇩🇪Schwerin, Germany
Klinikum der Hansestadt Stralsund GmbH-Ambulanz-Klinik für Psychiatrie und Psychotherapie - Germany
🇩🇪Stralsund, Germany
Aiginition Hospital of Athens
🇬🇷Athens, Greece
'Dafni' Psychiatric Hospital of Attica
🇬🇷Athens, Greece
Venizeleio General Hospital
🇬🇷Crete, Greece
Psychiatric Clinic 'Agios Charalampos'
🇬🇷Heraklion, Greece
University General Hospital of Ioannina
🇬🇷Ioannina, Greece
University General Hospital of Rio Patras
🇬🇷Patras, Greece
424 Military Hospital of Thessaloniki
🇬🇷Thessaloniki, Greece
Psychiatric Hospital of Thessaloniki
🇬🇷Thessaloniki, Greece
G Papanikolaou Hospital of Thessaloniki
🇬🇷Thessaloniki, Greece
Semmelweis Egyetem
🇭🇺Budapest, Hungary
Eszak Kozep budai Centrum Uj Szent Janos Korhaz es Szakrendelo Budai Csaladkozpontu
🇭🇺Budapest, Hungary
Processus Kft
🇭🇺Budapest, Hungary
Debreceni Egyetem, Kenézy Gyula Egyetemi Oktatókórház
🇭🇺Debrecen, Hungary
Bugat Pal Korhaz
🇭🇺Gyongyos, Hungary
Petz Aladar Megyei Oktato Korhaz
🇭🇺Gyor, Hungary
Bács-Kiskun Megyei Kórház a Szegedi Tudományegyetem Általános Orvostudományi Kar Oktató Kórháza
🇭🇺Kalocsa, Hungary
Szabolcs-Szatmar-Bereg Megyei Korhazak es Egyetemi Oktatokorhaz
🇭🇺Nyiregyhaza, Hungary
Pecsi Tudomanyegyetem Klinikai Kozpont
🇭🇺Pecs, Hungary
Rambam Medical Center
🇮🇱Haifa, Israel
Shalvata Mental Health Center
🇮🇱Hod Hasharon, Israel
Beer Yaakov Mental Health Center
🇮🇱Lod, Israel
Geha Mental Health Center
🇮🇱Petach Tikva, Israel
Sheba Medical Center
🇮🇱Ramat Gan, Israel
Tel Aviv Sourasky Medical Center
🇮🇱Telaviv, Israel
Republican Scientific and Practical Center of Mental Health
🇰🇿Almaty, Kazakhstan
Medical Center for Psychological Healt SME
🇰🇿Nur-Sultan, Kazakhstan
East-Kazakhstan Regional Centre of Mental Health
🇰🇿Ust'-Kamenogorsk, Kazakhstan
Chonnam National University Hospital
🇰🇷Gwangju, Korea, Republic of
Wonkwang University Hospital
🇰🇷Iksan, Korea, Republic of
KyungHee University Hospital
🇰🇷Seoul, Korea, Republic of
Korea University Anam Hospital
🇰🇷Seoul, Korea, Republic of
Severance Hospital Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Hospital Raja Permaisuri Bainun
🇲🇾Ipoh, Malaysia
Hospital Kuala Lumpur
🇲🇾Kuala Lumpur, Malaysia
University Malaya Medical Centre
🇲🇾Kuala Lumpur, Malaysia
Hospital Pengajar Universiti Putra Malaysia
🇲🇾Serdang, Malaysia
Hospital Tuanku Jaafar
🇲🇾Seremban, Malaysia
Brain Research Center
🇳🇱Amsterdam, Netherlands
AMC
🇳🇱Amsterdam, Netherlands
LUMC
🇳🇱Leiden, Netherlands
Haukeland University Hospital
🇳🇴Hordaland, Norway
Sykehuset Ostfold
🇳🇴Moss, Norway
St Olav University Hospital
🇳🇴Trondheim, Norway
Mlynowamed Specjalistyczny Psychiatryczny Gabinet Lekarski Joanna Lazarczyk
🇵🇱Bialystok, Poland
Osrodek Badan Klinicznych CLINSANTE S C
🇵🇱Torun, Poland
Uniwersyteckie Centrum Kliniczne
🇵🇱Gdansk, Poland
Centrum Badan Klinicznych PI House sp z o o
🇵🇱Gdansk, Poland
Centrum Medyczne Care Clinic Katowice
🇵🇱Katowice, Poland
Niepubliczny Zaklad Opieki Psychiatrycznej MENTIS
🇵🇱Leszno, Poland
Specjalistyczny Psychiatryczny Zespol Opieki Zdrowotnej w Lodzi Szpital im. J. Babinskiego
🇵🇱Lodz, Poland
SPZOZ CSK UM w Lodzi Klinika Zaburzen Afektywnych i Psychotycznych
🇵🇱Lodz, Poland
Centrum Medyczne Luxmed Sp z o o
🇵🇱Lublin, Poland
Hospital de Braga
🇵🇹Braga, Portugal
Centro Hospitalar do Tâmega e Sousa, EPE - Hospital Padre Americo, Vale do Sousa
🇵🇹Guilhufe - Penafiel, Portugal
Fund. Champalimaud
🇵🇹Lisboa, Portugal
Centro Hospitalar de Lisboa Norte Hospital Santa Maria
🇵🇹Lisboa, Portugal
Hosp. Cuf Tejo
🇵🇹Lisbon, Portugal