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| ID | Type | Description | Link |
|---|---|---|---|
| 2011-005200-15 | EudraCT Number |
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Low Enrollment
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The purpose of this study is to evaluate the safety and efficacy of filorexant (MK-6096) versus placebo as adjunctive treatment for major depressive disorder (MDD), in participants who are partial responders to antidepressant monotherapy with one of identified selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs), or bupropion. The primary hypothesis of the study is that filorexant is superior to placebo as augmentation therapy with respect to change from baseline to Week 6 in the Montgomery Asberg Depression Rating Scale (MADRS) total score.
Participants will continue to take their pretrial antidepressant medication as prescribed throughout the trial. Participants will be randomized in a 1:1 ratio to receive filorexant or placebo for a 6-week treatment period. Following completion of the treatment period, participants will enter a 2-week double-blind run-out period. During the run-out period, participants who received placebo in the 6-week treatment period will continue to receive placebo and participants who received filorexant in the 6-week treatment period will be randomized to receive either filorexant or placebo in a 1:1 ratio.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Filorexant 10 mg (Treatment Phase) | Experimental | Treatment Phase: Participants in this group were administered filorexant 10 mg once daily at bedtime for 6 weeks. |
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| Placebo (Treatment Phase) | Placebo Comparator | Treatment Phase: Participants in this group were administered placebo once daily at bedtime for 6 weeks. |
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| Filorexant 10 mg/Filorexant 10 mg (Run-out Phase) | Experimental | Run-out Phase: Following completion of the 6-week treatment phase, participants in this group were administered filorexant 10 mg once daily at bedtime for 2 weeks. Participants in this group had received filorexant 10 mg once daily during the treatment phase. |
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| Filorexant 10 mg/Placebo (Run-out Phase) | Placebo Comparator | Run-out Phase: Following completion of the 6-week treatment phase, participants in this group were administered placebo once daily at bedtime for 2 weeks. Participants in this group had received filorexant 10 mg once daily during the treatment phase. |
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| Placebo/Placebo (Run-out Phase) | Placebo Comparator |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Filorexant | Drug | Filorexant, one 10 mg tablet, orally, once daily at bedtime |
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| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline to Week 6 in Montgomery Asberg Depression Rating Scale (MADRS) Total Score | The MADRS is a 10-item clinician-rated instrument for evaluating severity of symptoms of depression. Each item is rated on a scale from 0 to 6, with total scores ranging from 0 to 60; higher scores correspond to greater symptom severity. The reported measure is the mean change from baseline to Week 6 of the Treatment Phase; improvement in symptoms is represented by negative values. | Baseline and Week 6 |
| Number of Participants With an Adverse Event (AE) During Treatment Phase | An AE is any unfavorable and unintended change in the structure, function or chemistry of the body temporally associated with study drug administration, whether or not considered related to the study drug. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with study drug administration, is also an AE. Participants with one or more AEs during the treatment phase (up to study Week 6) are counted once in this summary. | Up to Week 6 |
| Number of Participants Who Discontinued Study Drug Due to an AE During Treatment Phase | An AE is any unfavorable and unintended change in the structure, function or chemistry of the body temporally associated with study drug administration, whether or not considered related to the study drug. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with study drug administration, is also an AE. Participants who discontinued study drug treatment due to an AE during the treatment phase (up to study Week 6) are counted once in this summary. | Up to Week 6 |
| Number of Participants With an AE During Run-out Phase | An AE is any unfavorable and unintended change in the structure, function or chemistry of the body temporally associated with study drug administration, whether or not considered related to the study drug. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with study drug administration, is also an AE. Participants with one or more AEs during the 2-week run-out phase and/or during the 2-week follow up after the last dose of study drug, are counted once in this summary. |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline to Week 6 in MADRS Total Score Excluding the Sleep Item | The MADRS is a 10-item clinician-rated instrument for evaluating severity of symptoms of depression. Each item is rated on a scale from 0 to 6, with higher scores indicating greater symptom severity. The total score ranged from 0 to 54, with higher scores corresponding to greater symptom severity. This measure considered 9 of the 10 MADRS items: apparent sadness, reported sadness, inner tension, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts. It excluded "reduced sleep." The reported measure is the mean change from baseline to Week 6 of the Treatment Phase; improvement in symptoms is represented by negative values. |
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Inclusion Criteria:
Key Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Merck Sharp & Dohme LLC | Study Director |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28582570 | Result | Connor KM, Ceesay P, Hutzelmann J, Snavely D, Krystal AD, Trivedi MH, Thase M, Lines C, Herring WJ, Michelson D. Phase II Proof-of-Concept Trial of the Orexin Receptor Antagonist Filorexant (MK-6096) in Patients with Major Depressive Disorder. Int J Neuropsychopharmacol. 2017 Aug 1;20(8):613-618. doi: 10.1093/ijnp/pyx033. |
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During the 1-2 week screening period participants will be evaluated to determine if they meet study entry criteria. The screening period will serve as a wash-out period for participants taking prohibited medications.
One participant in the Filorexant 10 mg (Treatment Phase) arm did not receive study drug and was discontinued from the study; the reason given for discontinuation is given as "non-compliance with study drug".
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| ID | Title | Description |
|---|---|---|
| FG000 | Filorexant 10 mg (Treatment Phase) | Treatment Phase: Participants in this group were administered filorexant 10 mg once daily at bedtime for 6 weeks. |
| FG001 | Placebo (Treatment Phase) |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Treatment Phase |
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Run-out Phase: Following completion of the 6-week Treatment Phase, participants in this group were administered placebo once daily at bedtime for 2 weeks. Participants in this group had received placebo once daily during the Treatment Phase.
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| Placebo | Drug | Placebo, one tablet, orally, once daily at bedtime |
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| From first run-out dose (following Week 6 visit) up to 14 days after last dose of study drug (approximately 4 weeks) |
| Number of Participants Who Discontinued Study Drug Due to an AE During Run-out Phase | An AE is any unfavorable and unintended change in the structure, function or chemistry of the body temporally associated with study drug administration, whether or not considered related to the study drug. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) or a preexisting condition which is temporally associated with study drug administration, is also an AE. Participants who discontinued study drug treatment due to an AE during the 2-week run-out phase are counted once in this summary. | From first run-out dose (following Week 6 visit) up to Week 8 (2 weeks) |
| Baseline and Week 6 |
| Change From Baseline to Week 6 in the Hamilton Depression Rating Scale, 17-item Version (HAM-D17) Bech Subscale Score | The HAM-D, an instrument for evaluating severity of symptoms of depression, was completed by the participant. The instrument used in this study was the 17-item version (HAM-D17). The Bech subscale of the HAM-D17 is composed of 6 identified items out of the 17 items rated. Each item is rated on either a 3-point scale (0 to 2) or a 5-point scale (0 to 4). Total score ranged from 0 to 22, with a higher score indicating greater symptom severity. The following symptoms were rated on a 5-point scale (0-4): depressed mood, low self-esteem (guilt), work and interests, psychomotor retardation, and anxiety (psychic). The following symptom was rated on a 3-point scale (0-2): somatic symptoms (general). The reported measure is the change from baseline to Week 6 of the Treatment Phase; improvement in symptoms is represented by negative values. | Baseline and Week 6 |
| Percentage of Participants With HAM-D17 Remission (HAM-D17 Total Score ≤7) at Week 6 | The HAM-D, an instrument for evaluating severity of symptoms of depression, was completed by the participant. The instrument used in this study was the 17-item version (HAM-D17). Each item is rated on either a 3-point scale (0 to 2) or a 5-point scale (0 to 4), with higher scores indicating greater symptom severity. Total score ranged from 0 to 54. The following symptoms were rated on a 5-point scale (0-4): depressed mood, low self-esteem (guilt), suicidal thoughts, work and interests, psychomotor retardation, psychomotor agitation, anxiety (psychic), anxiety (somatic), and hypochondriasis (somatization). The following symptoms were rated on a 3-point scale (0-2): insomnia (initial), insomnia (middle), insomnia (late), gastrointestinal symptoms (appetite), somatic symptoms (general), sexual disturbances, insight, and weight loss. A participant with HAM-D17 total score ≤7 at Week 6 of the Treatment Phase was defined to have achieved HAM-D17 remission. | Week 6 |
Treatment Phase: Participants in this group were administered placebo once daily at bedtime for 6 weeks.
| FG002 | Filorexant 10 mg/Filorexant 10 mg (Run-out Phase) | Run-out Phase: Following completion of the 6-week treatment phase, participants in this group were administered filorexant 10 mg once daily at bedtime for 2 weeks. Participants in this group had received filorexant 10 mg once daily during the treatment phase. |
| FG003 | Filorexant 10 mg/Placebo (Run-out Phase) | Run-out Phase: Following completion of the 6-week treatment phase, participants in this group were administered placebo once daily at bedtime for 2 weeks. Participants in this group had received filorexant 10 mg once daily during the treatment phase. |
| FG004 | Placebo/Placebo (Run-out Phase) | Run-out Phase: Following completion of the 6-week Treatment Phase, participants in this group were administered placebo once daily at bedtime for 2 weeks. Participants in this group had received placebo once daily during the Treatment Phase. |
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| COMPLETED |
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| Run-out Phase |
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| ID | Title | Description |
|---|---|---|
| BG000 | Filorexant 10 mg (Treatment Phase) | Treatment Phase: Participants in this group were administered filorexant 10 mg once daily at bedtime for 6 weeks. |
| BG001 | Placebo (Treatment Phase) | Treatment Phase: Participants in this group were administered placebo once daily at bedtime for 6 weeks. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
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| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
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| Age, Continuous | Mean | Standard Deviation | Years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Primary | Change From Baseline to Week 6 in Montgomery Asberg Depression Rating Scale (MADRS) Total Score | The MADRS is a 10-item clinician-rated instrument for evaluating severity of symptoms of depression. Each item is rated on a scale from 0 to 6, with total scores ranging from 0 to 60; higher scores correspond to greater symptom severity. The reported measure is the mean change from baseline to Week 6 of the Treatment Phase; improvement in symptoms is represented by negative values. | Full Analysis Set (FAS) - population included participants who took ≥1 dose of study drug and had a baseline and Week 6 value. | Posted | Mean | Standard Deviation | score on a scale | Baseline and Week 6 |
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| Secondary | Change From Baseline to Week 6 in MADRS Total Score Excluding the Sleep Item | The MADRS is a 10-item clinician-rated instrument for evaluating severity of symptoms of depression. Each item is rated on a scale from 0 to 6, with higher scores indicating greater symptom severity. The total score ranged from 0 to 54, with higher scores corresponding to greater symptom severity. This measure considered 9 of the 10 MADRS items: apparent sadness, reported sadness, inner tension, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts. It excluded "reduced sleep." The reported measure is the mean change from baseline to Week 6 of the Treatment Phase; improvement in symptoms is represented by negative values. | Full Analysis Set (FAS) - population included participants who took ≥1 dose of study drug and had a baseline and Week 6 MADRS score. | Posted | Mean | Standard Deviation | score on a scale | Baseline and Week 6 |
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| Secondary | Change From Baseline to Week 6 in the Hamilton Depression Rating Scale, 17-item Version (HAM-D17) Bech Subscale Score | The HAM-D, an instrument for evaluating severity of symptoms of depression, was completed by the participant. The instrument used in this study was the 17-item version (HAM-D17). The Bech subscale of the HAM-D17 is composed of 6 identified items out of the 17 items rated. Each item is rated on either a 3-point scale (0 to 2) or a 5-point scale (0 to 4). Total score ranged from 0 to 22, with a higher score indicating greater symptom severity. The following symptoms were rated on a 5-point scale (0-4): depressed mood, low self-esteem (guilt), work and interests, psychomotor retardation, and anxiety (psychic). The following symptom was rated on a 3-point scale (0-2): somatic symptoms (general). The reported measure is the change from baseline to Week 6 of the Treatment Phase; improvement in symptoms is represented by negative values. | Full Analysis Set (FAS) - population included participants who took ≥1 dose of study drug and had a baseline and Week 6 HAM-D17 Beck Subscale score. | Posted | Mean | Standard Deviation | score on a scale | Baseline and Week 6 |
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| Secondary | Percentage of Participants With HAM-D17 Remission (HAM-D17 Total Score ≤7) at Week 6 | The HAM-D, an instrument for evaluating severity of symptoms of depression, was completed by the participant. The instrument used in this study was the 17-item version (HAM-D17). Each item is rated on either a 3-point scale (0 to 2) or a 5-point scale (0 to 4), with higher scores indicating greater symptom severity. Total score ranged from 0 to 54. The following symptoms were rated on a 5-point scale (0-4): depressed mood, low self-esteem (guilt), suicidal thoughts, work and interests, psychomotor retardation, psychomotor agitation, anxiety (psychic), anxiety (somatic), and hypochondriasis (somatization). The following symptoms were rated on a 3-point scale (0-2): insomnia (initial), insomnia (middle), insomnia (late), gastrointestinal symptoms (appetite), somatic symptoms (general), sexual disturbances, insight, and weight loss. A participant with HAM-D17 total score ≤7 at Week 6 of the Treatment Phase was defined to have achieved HAM-D17 remission. | Full Analysis Set (FAS) - population included participants who took ≥1 dose of study drug and had a baseline and Week 6 HAM-D17 score. | Posted | Number | percentage of participants | Week 6 |
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| Primary | Number of Participants With an Adverse Event (AE) During Treatment Phase | An AE is any unfavorable and unintended change in the structure, function or chemistry of the body temporally associated with study drug administration, whether or not considered related to the study drug. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with study drug administration, is also an AE. Participants with one or more AEs during the treatment phase (up to study Week 6) are counted once in this summary. | All Participants as Treated (APaT): Population includes participants who took ≥1 dose of study drug. | Posted | Number | Participants | Up to Week 6 |
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| Primary | Number of Participants Who Discontinued Study Drug Due to an AE During Treatment Phase | An AE is any unfavorable and unintended change in the structure, function or chemistry of the body temporally associated with study drug administration, whether or not considered related to the study drug. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with study drug administration, is also an AE. Participants who discontinued study drug treatment due to an AE during the treatment phase (up to study Week 6) are counted once in this summary. | All Participants as Treated (APaT): Population includes participants who took ≥1 dose of study drug. | Posted | Number | Participants | Up to Week 6 |
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| Primary | Number of Participants With an AE During Run-out Phase | An AE is any unfavorable and unintended change in the structure, function or chemistry of the body temporally associated with study drug administration, whether or not considered related to the study drug. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with study drug administration, is also an AE. Participants with one or more AEs during the 2-week run-out phase and/or during the 2-week follow up after the last dose of study drug, are counted once in this summary. | All Participants as Treated (APaT): Population includes participants who took ≥1 dose of study drug. | Posted | Number | Participants | From first run-out dose (following Week 6 visit) up to 14 days after last dose of study drug (approximately 4 weeks) |
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| Primary | Number of Participants Who Discontinued Study Drug Due to an AE During Run-out Phase | An AE is any unfavorable and unintended change in the structure, function or chemistry of the body temporally associated with study drug administration, whether or not considered related to the study drug. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) or a preexisting condition which is temporally associated with study drug administration, is also an AE. Participants who discontinued study drug treatment due to an AE during the 2-week run-out phase are counted once in this summary. | All Participants as Treated (APaT): Population includes participants who took ≥1 dose of study drug. | Posted | Number | Participants | From first run-out dose (following Week 6 visit) up to Week 8 (2 weeks) |
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Treatment Phase: Up to Week 6 Run-out Phase: From first run-out dose (following Week 6 visit) up to 14 days after last dose of study drug (approximately 4 weeks)
All Participants as Treated (APaT): Population includes participants who took ≥1 dose of study drug.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Filorexant 10 mg (Treatment Phase) | Treatment Phase: Participants in this group were administered filorexant 10 mg once daily at bedtime for 6 weeks. | 1 | 64 | 13 | 64 | ||
| EG001 | Placebo (Treatment Phase) | Treatment Phase: Participants in this group were administered placebo once daily at bedtime for 6 weeks. | 0 | 64 | 7 | 64 | ||
| EG002 | Filorexant 10 mg/Filorexant 10 mg (Run-out Phase) | Run-out Phase: Following completion of the 6-week treatment phase, participants in this group were administered filorexant 10 mg once daily at bedtime for 2 weeks. Participants in this group had received filorexant 10 mg once daily during the treatment phase. | 0 | 29 | 3 | 29 | ||
| EG003 | Filorexant 10 mg/Placebo (Run-out Phase) | Run-out Phase: Following completion of the 6-week treatment phase, participants in this group were administered placebo once daily at bedtime for 2 weeks. Participants in this group had received filorexant 10 mg once daily during the treatment phase. | 0 | 28 | 1 | 28 | ||
| EG004 | Placebo/Placebo (Run-out Phase) | Run-out Phase: Following completion of the 6-week treatment phase, participants in this group were administered placebo once daily at bedtime for 2 weeks. Participants in this group had received placebo once daily during the treatment phase. | 1 | 59 | 1 | 59 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Presyncope | Nervous system disorders | MedDRA 16.0 | Systematic Assessment |
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| Diverticulitis | Infections and infestations | MedDRA 16.0 | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Dizziness | Nervous system disorders | MedDRA 16.0 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 16.0 | Systematic Assessment |
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| Somnolence | Nervous system disorders | MedDRA 16.0 | Systematic Assessment |
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| Suicidal ideation | Psychiatric disorders | MedDRA 16.0 | Systematic Assessment |
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The Sponsor must have the opportunity to review all proposed abstracts, manuscripts, or presentations regarding this study 60 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Senior Vice President, Global Clinical Development | Merck Sharp & Dohme Corp. | 1-800-672-6372 | ClinicalTrialsDisclosure@merck.com |
| ID | Term |
|---|---|
| D003865 | Depressive Disorder, Major |
| D012008 | Recurrence |
| ID | Term |
|---|---|
| D003866 | Depressive Disorder |
| D019964 | Mood Disorders |
| D001523 | Mental Disorders |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| C573816 | MK-6096 |
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| Male |
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| Units | Counts |
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| OG002 | Placebo/Placebo (Run-out Phase) | Run-out Phase: Following completion of the 6-week Treatment Phase, participants in this group were administered placebo once daily at bedtime for 2 weeks. Participants in this group had received placebo once daily during the Treatment Phase. |
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| OG002 | Placebo/Placebo (Run-out Phase) | Run-out Phase: Following completion of the 6-week Treatment Phase, participants in this group were administered placebo once daily at bedtime for 2 weeks. Participants in this group had received placebo once daily during the Treatment Phase. |
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