Clinical trial NCT01554176: 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
Overall status: TERMINATED
Phase: PHASE2
Conditions: Major Depressive Disorder, Recurrent
Keywords: Current depressive episode
moderate to severe
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2012-03-14
Enrollment: 129
Sex: ALL
Minimum age (years): 21
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Change From Baseline to Week 6 in Montgomery Asberg Depression Rating Scale (MADRS) Total Score
timeFrame: Baseline and Week 6
measure: Number of Participants With an Adverse Event (AE) During Treatment Phase
timeFrame: Up to Week 6
measure: Number of Participants Who Discontinued Study Drug Due to an AE During Treatment Phase
timeFrame: Up to Week 6
measure: Number of Participants With an AE During Run-out Phase
timeFrame: From first run-out dose (following Week 6 visit) up to 14 days after last dose of study drug (approximately 4 weeks)
measure: Number of Participants Who Discontinued Study Drug Due to an AE During Run-out Phase
timeFrame: From first run-out dose (following Week 6 visit) up to Week 8 (2 weeks)
Secondary outcomes:
measure: Change From Baseline to Week 6 in MADRS Total Score Excluding the Sleep Item
timeFrame: Baseline and Week 6
measure: Change From Baseline to Week 6 in the Hamilton Depression Rating Scale, 17-item Version (HAM-D17) Bech Subscale Score
timeFrame: Baseline and Week 6
measure: Percentage of Participants With HAM-D17 Remission (HAM-D17 Total Score ≤7) at Week 6
timeFrame: Week 6
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
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.