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

Major Depressive Disorder, Recurrent Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01554176
• Other study ID #: 6096-022
• Secondary ID: 2011-005200-15
• Status: Terminated
• Phase: Phase 2
• Start date: May 18, 2012
• Est. completion date: September 3, 2013

Study information

• Verified date: October 2018
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 129
• Est. completion date: September 3, 2013
• Est. primary completion date: September 3, 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years to 64 Years

Eligibility

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.

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Major
• Disease
• Major Depressive Disorder, Recurrent
• Recurrence

Intervention

Drug:
• Filorexant
Filorexant, one 10 mg tablet, orally, once daily at bedtime
• Placebo
Placebo, one tablet, orally, once daily at bedtime

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.

References & Publications (1)

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 Neuro — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	Baseline and Week 6
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.	Up to Week 6
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.	Up to Week 6
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.	From first run-out dose (following Week 6 visit) up to 14 days after last dose of study drug (approximately 4 weeks)
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.	From first run-out dose (following Week 6 visit) up to Week 8 (2 weeks)
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.	Baseline and Week 6
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.	Baseline and Week 6
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.	Week 6