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

NCT01554176 | Terminated Phase 2 Results

• 2 other identifiers: 6096-0222011-005200-15
• Study Type: interventional
• Target: 129
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Major Depressive Disorder, Recurrent

Keywords

Current depressive episode; moderate to severe

Outcome Measures

Primary Outcomes (5)

• 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 Outcomes (3)

• Change From Baseline to Week 6 in MADRS Total Score Excluding the Sleep Item

  Baseline and Week 6

• Change From Baseline to Week 6 in the Hamilton Depression Rating Scale, 17-item Version (HAM-D17) Bech Subscale Score

  Baseline and Week 6

• Percentage of Participants With HAM-D17 Remission (HAM-D17 Total Score ≤7) at Week 6

  Week 6

Study Arms (5)

Filorexant 10 mg (Treatment Phase)

EXPERIMENTAL

Treatment Phase: Participants in this group were administered filorexant 10 mg once daily at bedtime for 6 weeks.

Drug: Filorexant

Placebo (Treatment Phase)

PLACEBO COMPARATOR

Treatment Phase: Participants in this group were administered placebo once daily at bedtime for 6 weeks.

Drug: Placebo

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.

Drug: Filorexant

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.

Drug: Filorexant; Drug: Placebo

Placebo/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 placebo once daily during the Treatment Phase.

Drug: Placebo

Interventions

Filorexant DRUG

Filorexant, one 10 mg tablet, orally, once daily at bedtime

Also known as: MK-6096

Filorexant 10 mg (Treatment Phase); Filorexant 10 mg/Filorexant 10 mg (Run-out Phase); Filorexant 10 mg/Placebo (Run-out Phase)

Placebo DRUG

Placebo, one tablet, orally, once daily at bedtime

Filorexant 10 mg/Placebo (Run-out Phase); Placebo (Treatment Phase); Placebo/Placebo (Run-out Phase)

Eligibility Criteria

• Age: 21 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related 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 Neuropsychopharmacol. 2017 Aug 1;20(8):613-618. doi: 10.1093/ijnp/pyx033.

  PMID: 28582570 RESULT

MeSH Terms

Conditions

Depressive Disorder, Major; Recurrence

Interventions

MK-6096

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 12, 2012
• First Posted: March 14, 2012
• Study Start: May 18, 2012
• Primary Completion: September 3, 2013
• Study Completion: September 3, 2013
• Last Updated: November 7, 2018
• Results First Posted: November 7, 2016

Record last verified: 2018-10

Data Sharing

• IPD Sharing: Will share