Safety and Efficacy of MK-6096 as Adjunctive Therapy in Participants With Major Depressive Disorder And Partial Response to Antidepressant Monotherapy (MK-6096-022)

Study Overview
=================
Brief Summary
-----------------
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.

Detailed Description
-----------------
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.

Official Title
-----------------
A Phase IIa, Multicenter, Randomized, Placebo-Controlled Clinical Trial to Evaluate the Safety and Efficacy of MK-6096 for Treatment Augmentation in Patients With Major Depressive Disorder

Conditions
-----------------
Major Depressive Disorder, Recurrent

Intervention / Treatment
-----------------
* Drug: Filorexant
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Participant is (a) male or (b) female and not of reproductive potential, or (c) female of reproductive potential has a serum beta-hCG level consistent with the nongravid state at screening and agrees to use acceptable contraception; Current primary diagnosis of recurrent major depressive disorder, without psychotic features, with a current moderate or severe depressive episode; Duration of the current major depressive episode must be at least 2 months but no more than 18 months at Screening; Participant has undergone an adequate trial of an antidepressant (one of identified SSRIs or SNRIs, or bupropion) for the current depressive episode. Key Exclusion Criteria: Current primary psychiatric diagnosis other than major depression; Lifetime diagnosis of bipolar disorder, schizophrenia, schizoaffective disorder, or other psychotic disorder; Alcohol or other substance abuse or dependence (excluding nicotine); Clinically significant abnormality or disease of the central nervous system (including dementia and other cognitive disorders or traumatic brain injury); Imminent risk of self-harm or of harm to others; Participant is a psychiatric inpatient; Participant has been on continuous antidepressant treatment for >18 months prior to Screening visit; Inadequate response to more than 3 adequate antidepressant trials (including the current antidepressant treatment trial) for treatment of the current depressive episode; Participant ever received electroconvulsive therapy, transcranial magnetic stimulation, or vagal nerve stimulation for treatment of depression; History of narcolepsy, cataplexy, circadian rhythm disorder, parasomnia, sleep-related breathing disorder, restless legs syndrome, periodic limb movement disorder, excessive daytime sleepiness or difficulty sleeping due to a medical condition; Clinical, laboratory, or electrocardiogram (ECG) evidence of significant systemic disease; Cardiovascular event (e.g., myocardial infarction) or procedure (e.g., coronary artery bypass surgery) within 3 months of study; History of malignancy ≤5 years prior to study, except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer; Body Mass Index >40 kg/m^2; Pregnancy, breast-feeding, or expecting to become pregnant.

Ages Eligible for Study
-----------------
Minimum Age: 21 Years
Maximum Age: 64 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Filorexant 10 mg (Treatment Phase)<br>Treatment Phase: Participants in this group were administered filorexant 10 mg once daily at bedtime for 6 weeks. | Drug: Filorexant<br>* Filorexant, one 10 mg tablet, orally, once daily at bedtime<br>* Other names: MK-6096;|
| Placebo Comparator: Placebo (Treatment Phase)<br>Treatment Phase: Participants in this group were administered placebo once daily at bedtime for 6 weeks. | Drug: Placebo<br>* Placebo, one tablet, orally, once daily at bedtime<br>|
| Experimental: Filorexant 10 mg/Filorexant 10 mg (Run-out Phase)<br>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. | Drug: Filorexant<br>* Filorexant, one 10 mg tablet, orally, once daily at bedtime<br>* Other names: MK-6096;|
| Placebo Comparator: Filorexant 10 mg/Placebo (Run-out Phase)<br>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. | Drug: Filorexant<br>* Filorexant, one 10 mg tablet, orally, once daily at bedtime<br>* Other names: MK-6096;Drug: Placebo<br>* Placebo, one tablet, orally, once daily at bedtime<br>|
| Placebo Comparator: Placebo/Placebo (Run-out Phase)<br>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. | Drug: Placebo<br>* Placebo, one tablet, orally, once daily at bedtime<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | 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. | 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) | 

Secondary Outcome Measures

| Outcome Measure | 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. | 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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Current depressive episode, moderate to severe