Back to resultsSafety and Efficacy of MK-6096 as Adjunctive Therapy in Participants With Major Depressive Disorder And Partial Response to Antidepressant Monotherapy (MK-6096-022)
Primary Purpose
Major Depressive Disorder, Recurrent
Status
Terminated
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Filorexant
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Major Depressive Disorder, Recurrent focused on measuring Current depressive episode, moderate to severe
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.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm Type
Experimental
Placebo Comparator
Experimental
Placebo Comparator
Placebo Comparator
Arm Label
Filorexant 10 mg (Treatment Phase)
Placebo (Treatment Phase)
Filorexant 10 mg/Filorexant 10 mg (Run-out Phase)
Filorexant 10 mg/Placebo (Run-out Phase)
Placebo/Placebo (Run-out Phase)
Arm Description
Treatment Phase: Participants in this group were administered filorexant 10 mg once daily at bedtime for 6 weeks.
Treatment Phase: Participants in this group were administered placebo once daily at bedtime for 6 weeks.
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.
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.
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.
Outcomes
Primary Outcome Measures
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.
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.
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.
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.
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.
Secondary Outcome Measures
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.
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.
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 Information
NCT ID
NCT01554176
First Posted
March 12, 2012
Last Updated
October 8, 2018
Sponsor
Merck Sharp & Dohme LLC
1. Study Identification
Unique Protocol Identification Number
NCT01554176
Brief Title
Safety and Efficacy of MK-6096 as Adjunctive Therapy in Participants With Major Depressive Disorder And Partial Response to Antidepressant Monotherapy (MK-6096-022)
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
Study Type
Interventional
2. Study Status
Record Verification Date
October 2018
Overall Recruitment Status
Terminated
Why Stopped
Low Enrollment
Study Start Date
May 18, 2012 (Actual)
Primary Completion Date
September 3, 2013 (Actual)
Study Completion Date
September 3, 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck Sharp & Dohme LLC
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Major Depressive Disorder, Recurrent
Keywords
Current depressive episode, moderate to severe
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
129 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Filorexant 10 mg (Treatment Phase)
Arm Type
Experimental
Arm Description
Treatment Phase: Participants in this group were administered filorexant 10 mg once daily at bedtime for 6 weeks.
Arm Title
Placebo (Treatment Phase)
Arm Type
Placebo Comparator
Arm Description
Treatment Phase: Participants in this group were administered placebo once daily at bedtime for 6 weeks.
Arm Title
Filorexant 10 mg/Filorexant 10 mg (Run-out Phase)
Arm Type
Experimental
Arm Description
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.
Arm Title
Filorexant 10 mg/Placebo (Run-out Phase)
Arm Type
Placebo Comparator
Arm Description
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.
Arm Title
Placebo/Placebo (Run-out Phase)
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Filorexant
Other Intervention Name(s)
MK-6096
Intervention Description
Filorexant, one 10 mg tablet, orally, once daily at bedtime
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo, one tablet, orally, once daily at bedtime
Primary Outcome Measure Information:
Title
Change From Baseline to Week 6 in Montgomery Asberg Depression Rating Scale (MADRS) Total Score
Description
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.
Time Frame
Baseline and Week 6
Title
Number of Participants With an Adverse Event (AE) During Treatment Phase
Description
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.
Time Frame
Up to Week 6
Title
Number of Participants Who Discontinued Study Drug Due to an AE During Treatment Phase
Description
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.
Time Frame
Up to Week 6
Title
Number of Participants With an AE During Run-out Phase
Description
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.
Time Frame
From first run-out dose (following Week 6 visit) up to 14 days after last dose of study drug (approximately 4 weeks)
Title
Number of Participants Who Discontinued Study Drug Due to an AE During Run-out Phase
Description
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.
Time Frame
From first run-out dose (following Week 6 visit) up to Week 8 (2 weeks)
Secondary Outcome Measure Information:
Title
Change From Baseline to Week 6 in MADRS Total Score Excluding the Sleep Item
Description
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.
Time Frame
Baseline and Week 6
Title
Change From Baseline to Week 6 in the Hamilton Depression Rating Scale, 17-item Version (HAM-D17) Bech Subscale Score
Description
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.
Time Frame
Baseline and Week 6
Title
Percentage of Participants With HAM-D17 Remission (HAM-D17 Total Score ≤7) at Week 6
Description
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.
Time Frame
Week 6
10. Eligibility
Sex
All
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
64 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Merck Sharp & Dohme LLC
Official's Role
Study Director
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
IPD Sharing URL
http://engagezone.msd.com/ds_documentation.php
Citations:
PubMed Identifier
28582570
Citation
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.
Results Reference
result
Learn more about this trial
Safety and Efficacy of MK-6096 as Adjunctive Therapy in Participants With Major Depressive Disorder And Partial Response to Antidepressant Monotherapy (MK-6096-022)
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