MDD POC Study GSK372475 Subjects Depressive Disease

Depressive Disorder Clinical Trial

Official title:

A Ten-week, Multicenter, Randomized, Double-Blind, Placebo-and Active-Controlled, Paralleled-Group, Flexible-Dose Study Evaluating the Efficacy, Safety and Tolerability of GSK372475 or Paroxetine Compared to Placebo in Adult Subjects Diagnosed With Major Depressive Disorder

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00420641
• Other study ID #: SND 103288
• Status: Completed
• Phase: Phase 2
• First received: January 10, 2007
• Last updated: July 17, 2017
• Start date: December 19, 2006
• Est. completion date: October 15, 2008

Study information

• Verified date: October 2014
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

To evaluate the efficacy, safety and tolerability of GSK372475 compared with placebo in the treatment of outpatients subjects with major depressive disorder to exhibit decreased pleasure, interest and energy.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 492
• Est. completion date: October 15, 2008
• Est. primary completion date: June 1, 2008
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 64 Years

Eligibility

Inclusion criteria:

• Major depressive episode (MDE) associated with Major Depressive Disorder (DSM-IV-TR criteria)

• Duration of current episode is at least 12 weeks duration and less than 2 years

• Symptoms of decreased energy, pleasure, and interest

• Female subjects who agree to use acceptable methods of birth control throughout the study

Exclusion criteria:

• Current diagnosis of Panic Disorder, or symptoms of generalized anxiety or panic attacks that could interfere with their ability to complete the trial

• Symptoms of MDE better accounted for by another diagnosis

• Diagnosis of panic disorder / attacks, generalised anxiety, borderline or antisocial personality disorder, dementia, anorexia nervosa / bulimia (within 6 months of screening), bipolar disorder, schizophrenia or any other psychotic disorder(s).

• Started psychotherapy within 3 months prior to the Screening

• Received electroconvulsive therapy or transcranial magnetic stimulation within 6 months prior to screening

• Received psychoactive drugs within 4 weeks of randomization

• Positive urine drug screen or positive blood alcohol

• Suicidal risk or has had any previous suicide attempt, a family history of suicide attempt

• Positive pregnancy test

• History of seizure disorder, myocardial infarction (< 1yr), or unstable medical condition

• Failed to respond to an adequate course of pharmacotherapy of at least 2 different antidepressants

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Major

Intervention

Drug:
• GSK372475
GSK372475 1.0-1.5 mg/day
• Paroxetine
Paroxetine 20-30 mg/day

Other:
• Placebo
Placebo to Match

Locations

Country	Name	City	State
Bulgaria	GSK Investigational Site	Plovdiv
Bulgaria	GSK Investigational Site	Sofia
Canada	GSK Investigational Site	Burlington	Ontario
Canada	GSK Investigational Site	Markham	Ontario
Canada	GSK Investigational Site	Miramichi	New Brunswick
Canada	GSK Investigational Site	Mississauga	Ontario
Chile	GSK Investigational Site	Providencia / Santiago	Región Metro De Santiago
Chile	GSK Investigational Site	Santiago	Región Metro De Santiago
Chile	GSK Investigational Site	Santiago	Región Metro De Santiago
Costa Rica	GSK Investigational Site	Los Yoses, San José	San José
Costa Rica	GSK Investigational Site	San José
Croatia	GSK Investigational Site	Split
Croatia	GSK Investigational Site	Zagreb
France	GSK Investigational Site	Angoulême
France	GSK Investigational Site	Dole
France	GSK Investigational Site	Elancourt
France	GSK Investigational Site	Paris
France	GSK Investigational Site	Toulouse
France	GSK Investigational Site	Toulouse
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Dresden	Sachsen
Germany	GSK Investigational Site	Huettenberg	Hessen
Germany	GSK Investigational Site	Nuernberg	Bayern
India	GSK Investigational Site	Bangalore
India	GSK Investigational Site	Bangalore
India	GSK Investigational Site	Lucknow
India	GSK Investigational Site	Mangalore
India	GSK Investigational Site	Manipal,
Italy	GSK Investigational Site	Milano	Lombardia
Italy	GSK Investigational Site	Pisa	Toscana
Poland	GSK Investigational Site	Bialystok
Poland	GSK Investigational Site	Chelmno
Poland	GSK Investigational Site	Leszno

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

Bulgaria,  Canada,  Chile,  Costa Rica,  Croatia,  France,  Germany,  India,  Italy,  Poland, 

References & Publications (1)

Learned S, Graff O, Roychowdhury S, Moate R, Krishnan KR, Archer G, Modell J, Alexander R, Zamuner S, Lavergne A, Evoniuk G, Ratti E. Results of Two Double-Blind, Placebo- and Active-Controlled Studies of GSK372475, a Triple Monoamine Reuptake Inhibitor, in the Treatment of Major Depressive Disorder. [J Psychopharmacol EPublication ahead of print. DOI 10.1177/0269881111424931]. 2011;

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean Change From Randomization at the End of the Treatment Phase in the MADRS Total Score	The MADRS scale measures the depression level of a participant. The total score was derived by adding the scores of the following 10 items: 1, apparent sadness; 2, reported sadness; 3, inner tension; 4, reduced sleep; 5, reduced appetite; 6, concentration difficulties; 7, lassitude; 8, inability to feel; 9, pessimistic thoughts; 10, suicidal thoughts. Each item was scored using a scale of 0 to 6 (a higher score indicates increased severity). The maximum total score is 60; 0, no depression; 60, severely depressed. Randomization value was defined as the assessment value done on Week 0. Change from Randomization in total score was the difference between MADRS total score at the time point being analyzed (Week 10) to Randomization.	Week 0 (Randomization) and Week 10
Primary	Change From Randomization at the End of the Treatment Phase (Week 10) in Bech Scale (6-item of 17-item Hamilton Depression Rating [HAMD-17] Scale) Score	The HAMD is a rating instrument for evaluating severity of symptoms of depression, was completed by the participant. The rating instrument used in this study was the 17-item version (HAM-D17). The Bech scale of the HAMD-17 is composed of 6 identified items out of the 17 items rated in HAMD-17 scale. Each item is rated on either a 3-point scale (0 to 2) or a 5-point scale (0 to 4). The following symptoms were rated on a 5-point scale (0-4): depressed mood, feeling of guilt, work and interests, psychomotor retardation, and anxiety (psychic). The following symptom was rated on a 3-point scale (0-2): somatic symptoms (general). Total score ranged from 0 to 22, with 0 indicating absence of symptoms and a higher score indicating greater severity of symptoms. Randomization value was defined as the assessment value done on Week 0. Change from Randomization in total score was the difference between Bech total score at the time point being analyzed (Week 10) to Randomization.	Week 0 (Randomization) and Week 10
Primary	Mean Change From Randomization at the End of the Treatment Phase (Week 10) in Inventory of Depressive Symptomatology-Clinician Rated (IDS-CR) Total Score	The IDS-CR is a standardized 30-item, clinician rated scale to assess the severity of a participant's depressive symptoms. The items were rated on a 4-point scale of 0-3, where 0 indicated absence of symptom and higher score indicated greater severity of symptom. In order to calculate the total score of IDS-CR, the following procedures were used: either item 11 or 12 were scored; either item 13 or 14 were scored; if both items 11 and 12 (or 13 and 14) were scored, the highest of the items was scored. The total score was obtained by adding the scores of 28 items of the 30 items. Total scores range from 0-84, with a score of 0 indicating no depression and a score of 84 indicating the most severe depression. Randomization value was defined as the assessment value done on Week 0. Change from Randomization in total score was the difference between IDS-CR total score at the time point being analyzed (Week 10) to Randomization.	Week 0 (Randomization) and Week 10
Secondary	Mean Change From Randomization in IDS- Self-Rated Version (SR) Total Score Over Week 10	The IDS-SR is a standardized 30-item, participant rated scale to assess the severity of a participant's depressive symptoms. The items were rated on a 4-point scale of 0-3, where 0 indicated absence of symptom and higher score indicated greater severity of symptom. In order to calculate the total score of IDS-SR, the following procedures were used: either item 11 or 12 were scored; either item 13 or 14 were scored; if both items 11 and 12 (or 13 and 14) were scored, the highest of the items was scored. The total score was obtained by adding the scores of 28 items of the 30 items. Total scores range from 0-84, with a score of 0 indicating no depression and a score of 84 indicating the most severe depression. Randomization value was defined as the assessment value done on Week 0. Change from Randomization in total score was the difference between IDS-SR total score at the individual time points being analyzed (Week, 1, 4 and 10) to Randomization.	Week 0 (Randomization) up to Week 10
Secondary	Mean Change From Randomization in the 16-item Quick Inventory of Depressive Symptomatology-Clinician-rated Version (QIDS-CR16) Total Score Over Week 10	QIDS-CR16 is a 16-item rating scale of depressive symptoms rated by the clinician. The items were rated on a 4-point scale of 0-3, where 0 indicated absence of symptom and higher score indicated greater severity of symptom. Total score was obtained by adding scores of items of sad mood, interest, energy/fatigue, sleep disturbance, decrease/increase in appetite or weight, concentration/decision making, suicidal ideation and psychomotor agitation/retardation, the highest score on any 1 of the 4 sleep items, highest score on any 1 appetite/weight item and highest score on either of the 2 psychomotor items. Total scores range from 0-27, with a score of 0 indicating no depression and a score of 27 indicating most severe depression. Randomization value was defined as the assessment value done on Week 0. Change from Randomization in total score was the difference between QIDS-CR16 total score at the individual time points being analyzed (Week 1, 2, 3, 4, 5, 6, 8 and 10) to Randomization.	Week 0 (Randomization) up to Week 10
Secondary	Mean Change From Randomization in the 16-item Quick Inventory of Depressive Symptomatology-Self-rated Version (QIDS-SR16) Total Score Over Week 10	QIDS-SR16 is a 16-item rating scale of depressive symptoms completed by participant. The items were rated on a 4-point scale of 0-3, where 0 indicated absence of symptom and higher score indicated greater severity of symptom. Total score was obtained by adding scores of the items of sad mood, interest, energy/fatigue, sleep disturbance, decrease/increase in appetite or weight, concentration/decision making, suicidal ideation and psychomotor agitation/retardation, the highest score on any 1 of the 4 sleep items, highest score on any 1 appetite/weight item and highest score on either of the 2 psychomotor items. Total scores range from 0-27, with a score of 0 indicating no depression and a score of 27 indicating most severe depression. Randomization value was defined as the assessment value done on Week 0. Change from Randomization in total score was the difference between QIDS-SR16 total score at the individual time points being analyzed (Week 1, 4 and 10) to Randomization.	Week 0 (Randomization) up to Week 10
Secondary	Mean Change From Randomization in the MADRS Item 2 Score (Reported Sadness) Over Week 10	The MADRS scale measures the depression level of a participant. The items of the scale include: 1, apparent sadness; 2, reported sadness; 3, inner tension; 4, reduced sleep; 5, reduced appetite; 6, concentration difficulties; 7, lassitude; 8, inability to feel; 9, pessimistic thoughts; 10, suicidal thoughts. The item 2 (Reported Sadness) of MADRS was scored using a scale 7-point scale of 0-6, where 0 indicates absence of symptom and higher score indicates increased severity of symptom. Randomization value was defined as the assessment value done on Week 0. Change from Randomization in total score was the difference between MADRS Item 2 score at the time points being analyzed (Week 1, 2, 3, 4, 5, 6, 8 and 10) to Randomization.	Week 0 (Randomization) up to Week 10
Secondary	Mean Change From Randomization in the IDS-CR Scale Item 5 (Feeling Sad) Over Week 10	The IDS-CR is a standardized 30-item, clinician rated scale to assess the severity of a participant's depressive symptoms. The item 5 (Feeling Sad) of IDS-CR was rated on a 4-point scale of 0-3, where 0 indicated absence of symptom and higher score indicated greater severity of symptom. Randomization value was defined as the assessment value done on Week 0. Change from Randomization in score was the difference between IDS-CR Item 5 score at the time points being analyzed (Week 1, 2, 3, 4, 5, 6, 8 and 10) to Randomization.	Week 0 (Randomization) up to Week 10
Secondary	Mean Change From Randomization at the End of the Treatment Phase (Week 10) in the HAMD-17 Total Score	HAMD-17 is a standardized, clinician-administered rating scale that assesses 17 items characteristically associated with major depression. Items of HAMD-17 are rated on a scale 3-point scale of 0-2 or a 5-point scale of 0-4 where 0 is absence of symptom and higher score indicate more severe symptom. Items rated on the 3-point scale include: insomnia early, middle, late; somatic symptoms gastrointestinal and general; genital symptoms; loss of weight; insight. Items rated on 5-point scale include: depressed mood; feelings of guilt; suicide; work and activities; retardation; agitation; anxiety psychic and somatic; hypochondriasis. Total score ranges from 0 to 52, where 0 indicates absence of symptom and higher scores indicates more severe symptoms. Randomization value was defined as the assessment value done on Week 0. Change from Randomization in total score was the difference between HAMD-17 total score at the time point being analyzed (Week 10) to Randomization.	Week 0 (Randomization) and Week 10
Secondary	Mean Change From Randomization in the HAMD-17 Scale Item 1 (Depressed Mood) Over Week 10	HAMD-17 is a standardized, clinician-administered rating scale that assesses 17 items characteristically associated with major depression (symptoms such as depressed mood, work and activities, sleep, suicide, psychomotor agitation/retardation, appetite, sexual interest, anxiety, and somatic symptoms). The items of the HAMD-17 are rated on a 3-point scale of 0-2 or a 5-point scale of 0-4. The item 1 (Depressed Mood) of HAMD-17 was rated the 5-point scale of 0-4, where 0 indicates absence of symptom and higher score indicates more severe symptom. Randomization value was defined as the assessment value done on Week 0. Change from Randomization in the score was the difference between HAMD-17 Item 1 score at the individual time points being analyzed (Week 1, 2, 3, 4, 5, 6, 8 and 10) to Randomization.	Week 0 (Randomization) up to Week 10
Secondary	Mean Change From Randomization in IDS-CR and IDS-SR 5 Item Subscale Over Week 10	The IDS-CR and IDS-SR is a standardized 30-item scale rated by the clinician and the participant respectively to assess the severity of a participant's depressive symptoms. The 5 items of the IDS subscale include: item 19 (general interest/involvement), item 20 (energy/fatigability), item 21 (pleasure/enjoyment), item 22 (sexual interest), item 30 (Leaden paralysis/physical energy) which assessed participant's pleasure, interest and energy. The items were rated on a 4-point scale of 0-3, where 0 indicated absence of symptom and higher score indicated greater severity of symptom. Total score ranges from 0 to 15, where 0 indicates absence of symptom and higher scores indicates more severe symptoms. Randomization value was defined as the assessment value done on Week 0. Change from Randomization in total score was the difference between IDS 5 Item subscale total score at the individual time points being analyzed (Week 1, 2, 3, 4, 5, 6, 8 and 10) to Randomization.	Week 0 (Randomization) up to Week 10
Secondary	Mean Change From Randomization in the Clinical Global Impression-Severity of Illness (CGI-S) Scale Over Week 10	The CGI-S scale measures the severity of psychiatric symptoms on a 7-point scale from 1-7. The scores indicated the following: 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. The score ranged from 1-7, where 1 indicated absence of symptoms and higher score indicated greater severity of symptoms. Randomization value was defined as the assessment value done on Week 0. Change from Randomization in the score was the difference between CGI-S score at the individual time points being analyzed (Week 1, 2, 3, 4, 5, 6, 8 and 10) to Randomization.	Week 0 (Randomization) up to Week 10
Secondary	Mean Change From Randomization in the Motivation and Energy Inventory (MEI) 18-Item Short Form (SF) Total Score Over Week 10	MEI 18 item-SF questionnaire was used to measure reductions in mental energy, physical energy, and social motivation. All items use either a 7-level (0-6) or 5-level (0-4) response scale; for questions 1, 2, and 13-18, response '0' indicates lower motivation, energy and interest and responses with higher scores indicate increased motivation, energy and interest. For questions 3-12, response '0' indicates higher motivation, energy and interest and responses with higher scores indicate lower motivation, energy and interest. Items with a 5-level response scale were rescaled to 7-levels, and items were reverse-scored. Total score ranges from 0-108, where 0 indicates lower motivation, energy and interest and higher score indicates higher motivation, energy and interest. Randomization value was defined as assessment value done on Week 0. Change from Randomization in total score was difference between MEI score at individual time points being analyzed (Week 1, 4 and 10) to Randomization.	Week 0 (Randomization) up to Week 10
Secondary	Mean Change From Randomization in the Changes in Sexual Functioning Questionnaire 14-item Short Form (CSFQ-14SF) Over Week 10	The CSFQ-14SF is a structured self reported questionnaire designed to measure illness- and medication-related changes in sexual functioning. It is consisting of 14 items that measure sexual activity and sexual functioning. It measures five dimensions of sexual behavior: pleasure (1 item); desire/frequency (items 2 and 3); desire/interest (items 4, 5 and 6); arousal (items 7, 8 and 9); and orgasm (items 11, 12 and 13). Items 10 and 14 are included in the total score but not in any dimension score. Items were rated on an 5 point scale from 1 to 5. Total score ranged from 14 to 70, where higher scores indicate higher sexual functioning and lower score indicate lower sexual functioning. Randomization value was defined as the assessment value done on Week 0. Change from Randomization in the total score was the difference between CSFQ-14SF score at the individual time points being analyzed (Week 4 and 10) to Randomization.	Week 0 (Randomization) up to Week 10
Secondary	Mean Change From Randomization in the MADRS Total Score Over Week 8	The MADRS scale measures the depression level of a participant. The total score was derived by adding the scores of the following 10 items: 1, apparent sadness; 2, reported sadness; 3, inner tension; 4, reduced sleep; 5, reduced appetite; 6, concentration difficulties; 7, lassitude; 8, inability to feel; 9, pessimistic thoughts; 10, suicidal thoughts. Each item was scored using a scale of 0 to 6 (a higher score indicates increased severity). The total score ranged from 0-60, where 0 indicated no depression and 60 indicated severely depressed. Randomization value was defined as the assessment value done on Week 0. Change from Randomization in total score was the difference between MADRS total score at the time points being analyzed (Week 1, 2, 3, 4, 5, 6 and 8) to Randomization.	Week 0 (Randomization) up to Week 8
Secondary	Mean Change From Randomization in IDS-CR Total Score Over Week 8	The IDS-CR is a standardized 30-item, clinician rated scale to assess the severity of a participant's depressive symptoms. The items were rated on a 4-point scale of 0-3, where 0 indicated absence of symptom and higher score indicated greater severity of symptom. In order to calculate the total score of IDS-CR, the following procedures were used: either item 11 or 12 were scored; either item 13 or 14 were scored; if both items 11 and 12 (or 13 and 14) were scored, the highest of the items was scored. The total score was obtained by adding the scores of 28 items of the 30 items. Total scores range from 0-84, with a score of 0 indicating no depression and a score of 84 indicating the most severe depression. Randomization value was defined as the assessment value done on Week 0. Change from Randomization in total score was the difference between IDS-CR total score at the time points being analyzed (Week 1, 2, 3, 4, 5, 6 and 8) to Randomization.	Week 0 (Randomization) up to Week 8
Secondary	Mean Change From Randomization in the in Bech Scale (6-item of HAMD-17 Scale) Score Over Week 8	The HAMD is a rating instrument for evaluating severity of symptoms of depression, was completed by the participant. Rating instrument used in this study was the 17-item version (HAM-D17). The Bech scale of the HAMD-17 is composed of 6 identified items out of the 17 items rated in HAMD-17 scale. Each item is rated on either a 3-point scale (0 to 2) or a 5-point scale (0 to 4). The following symptoms were rated on a 5-point scale (0-4): depressed mood, feeling of guilt, work and interests, psychomotor retardation, and anxiety (psychic). The following symptom was rated on a 3-point scale (0-2): somatic symptoms (general). Total score ranged from 0 to 22, with 0 indicating absence of symptoms and a higher score indicating greater severity of symptoms. Randomization value was defined as the assessment value done on Week 0. Change from Randomization in total score was the difference between Bech total score at the time points being analyzed (Week 1, 2, 3, 4, 5, 6 and 8) to randomization.	Week 0 (Randomization) up to Week 8
Secondary	Percentage of Responders and Remitters of MADRS Over Week 10	The MADRS scale measures the depression level of a participant. The total score was derived by adding the scores of the following 10 items: 1, apparent sadness; 2, reported sadness; 3, inner tension; 4, reduced sleep; 5, reduced appetite; 6, concentration difficulties; 7, lassitude; 8, inability to feel; 9, pessimistic thoughts; 10, suicidal thoughts. Each item was scored using a scale of 0 to 6 (a higher score indicates increased severity). The total score ranged from 0-60, where 0 indicated no depression and 60 indicated severely depressed. Responders were defined as participants who had a >=50% reduction from randomization in MADRS total Score. Percentage change from randomization was calculated as total score at post Randomization visit minus total score at Randomization visit divided by total score at Randomization visit multiplied by 100. Remitters were defined as participants with a MADRS total score <=11.	Up to Week 10
Secondary	Percentage of Responders and Remitters of IDS-CR Over Week 10	IDS-CR is a standardized 30-item, clinician rated scale to assess the severity of a participant's depressive symptoms. The items were rated on a 4-point scale of 0-3, where 0 indicated absence of symptom and higher score indicated greater severity of symptom. Total score of IDS-CR calculated as : either item 11 or 12 scored; either item 13 or 14 scored; if both items scored, the highest of the items was used. Total score was obtained by adding the scores of 28 items of the 30 items. Total scores range from 0-84, with a score of 0 indicating no depression and a score of 84 indicating the most severe depression. Responders were defined as participants who had a >=50% reduction from randomization in IDS-CR total Score. Percentage change from randomization was calculated as total score at post Randomization visit minus total score at Randomization visit divided by total score at Randomization visit multiplied by 100. Remitters were defined as participants with a IDS-CR total score <=14.	Up to Week 10
Secondary	Percentage of Responders and Remitters of HAMD-17 Over Week 10	HAMD-17 is a standardized, clinician-administered rating scale that assesses 17 items characteristically associated with major depression (symptoms such as depressed mood, work and activities, sleep, suicide, psychomotor agitation/retardation, appetite, sexual interest, anxiety, and somatic symptoms). The items of the HAMD-17 are rated on a scale of 0 to 2 or 0 to 4, and the total score ranges from 0 to 52, where 0 indicates absence of symptom and higher scores indicates more severe symptoms. Responders were defined as participants who had a >=50% reduction from randomization in HAMD-17 total Score. Percentage change from randomization was calculated as total score at post Randomization visit minus total score at Randomization visit divided by total score at Randomization visit multiplied by 100. Remitters were defined as participants with a HAMD-17 total score <=7.	Up to Week 10
Secondary	Percentage of Participants With Clinical Global Impression - Global Improvement (CGI-I) Over Week 10	The CGI-I scale measures the improvement of psychiatric symptoms on a 7-point scale from 1-7. The scale was rated by the clinician at every visit during the treatment phase (Week 1 through Week 10/early withdrawal) of the participant's total improvement or worsening compared with that individual's condition at the start of the study (the Randomization visit , Week 0) whether or not the change is judged to be due to drug treatment. The scores indicated the following: 1= very much improved; 2= much improved; 3= minimally improved; 4= no change; 5= minimally worse; 6= much worse; 7= very much worse. The score ranged from 1-7, where 1 indicated very much improved and higher score indicated greater severity of symptoms. Randomization value was defined as the assessment value done on Week 0. Data is reported for the percentage of participants who were much improved and very much improved.	Up to Week 10
Secondary	Percentage of Participants Satisfied With Study Medication at Week 10	Participants were asked complete the participant Satisfaction with Study Medication question at Week 10 (or early withdrawal). Satisfaction was measured using a single 7-point Likert scale from 1 to 7 where higher scores indicate greater satisfaction with study medication. A score of 1 represents very dissatisfied, whilst a score of 7 represents very satisfied. Participants were categorized as a responder if they are rated either as 6 "Satisfied" or 7 "Very Satisfied". The proportion of responders as percentage of participants based on the participant satisfaction with study medication item was defined as: number of participants with a response of 6 or 7 at the visit divided by number of participants with a satisfaction with study medication assessment at that visit (the sum of responders and non-responders) multiplied by 100.	Week 10
Secondary	Number of Participants With Most Severe Suicidal Behaviour and Ideation in the Suicidal Behavior (SB) and Suicidal Ideation (SI) Subscales of the Columbia Suicide Severity Rating Scale (CSSRS) Over Week 10	CSSRS is a clinician-rated scale that evaluates severity and change of suicidality by integrating both behaviour and ideation. For SB scale, participants were scored as "non-suicidal" (00), "preparatory acts or behavior communicating ideation" (01), "aborted attempt" (02), "interrupted attempt" (03) or "actual attempt" (04) based on the most severe score (4 being the most severe). On SI scale, participants were scored as "non-suicidal" (00), "wish to be dead" (01), "non-specific active suicidal thoughts" (02), "active suicidal ideation with associated thoughts of methods without intent" (03), "active suicidal ideation with some intent to act on suicidal thoughts without clear plan" (04), "active suicidal ideation with plan and intent" (05), based on the most severe score (5 being the most severe). For both subscales, 0 indicated absence of symptom and higher score indicated greater severity of symptom. Only those scores for which at least one participant was reported are summarized.	Up to Week 10