Major Depressive Disorder (MDD), Major Depressive Disorder With Psychotic Features
Conditions
Keywords
Major Depressive Disorder, Antidepressant Inadequate Response, Adjunctive Therapy, Randomized Double-Blind Placebo-Controlled
Brief summary
This Phase 3, multicenter, randomized, double-blind, placebo-controlled clinical trial is designed to evaluate the efficacy and safety of lurasidone as adjunctive therapy in adult patients with major depressive disorder (MDD) who show an inadequate response to antidepressant monotherapy. Eligible participants will continue their background antidepressant treatment and be randomized to receive either lurasidone (20, 40, or 60 mg/day) or placebo for 8 weeks. The primary endpoint is the change from baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score at Week 8. Secondary endpoints include response and remission rates, changes in Clinical Global Impression-Severity (CGI-S), 17-item Hamilton Depression Rating Scale (HAM-D17), Hamilton Anxiety Rating Scale (HAM-A), and Sheehan Disability Scale (SDS) scores. Safety assessments will include adverse events, laboratory tests, electrocardiograms (ECGs), vital signs, and suicidality monitoring Columbia-Suicide Severity Rating Scale (C-SSRS).
Detailed description
Major depressive disorder (MDD) is a common psychiatric condition, and many patients fail to achieve adequate improvement with antidepressant monotherapy. Adjunctive therapies are therefore needed to improve outcomes. Lurasidone, an atypical antipsychotic, has shown potential benefit when combined with antidepressants. This study will enroll up to 364 adult outpatients aged 19-64 years who meet Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for MDD and demonstrate inadequate response to at least one antidepressant. Participants must have a MADRS score ≥24 and CGI-S score ≥4 at both screening and baseline. After a screening/washout period of up to 14 days, subjects will be randomized 1:1 to lurasidone or placebo, in addition to their ongoing antidepressant. Treatment period: 8 weeks of double-blind therapy, with dose titration allowed in the first 2 weeks and fixed dosing thereafter. Follow-up: 1 week safety follow-up after last dose. Primary objective: To assess whether adjunctive lurasidone significantly improves depressive symptoms compared to placebo, measured by MADRS total score change from baseline to Week 8. Secondary objectives: To evaluate response and remission rates, functional improvement (SDS), and changes in anxiety and depression severity scales (HAM-A, HAM-D17, CGI-S). Safety objectives: To monitor adverse events, extrapyramidal symptoms (Abnormal Involuntary Movement Scale (AIMS), Barnes Akathisia Rating Scale (BARS), Simpson-Angus Scale (SAS)), suicidality (Columbia-Suicide Severity Rating Scale (C-SSRS)), laboratory values, electrocardiograms (ECGs), and vital signs. This trial will provide important evidence on the role of lurasidone as adjunctive therapy for patients with MDD who do not respond adequately to antidepressant monotherapy.
Interventions
DRUGLurasidone
Lurasidone
DRUGPlacebo
Placebo
DRUGBackground Antidepressant Therapy
Background Antidepressant treatment (ADT)
Sponsors
Bukwang Pharmaceutical
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Double-blind: Participant, Care Provider, Investigator, Outcomes Assessor are all masked; Randomization and blinding procedures ensure neither participants nor study staff know treatment assignment until unblinding.
Intervention model description
Participants will be randomized in a 1:1 ratio to receive adjunctive lurasidone (20, 40, or 60 mg/day) or placebo, in addition to ongoing antidepressant therapy, for 8 weeks.
Eligibility
Sex/Gender
ALL
Age
19 Years to 64 Years
Healthy volunteers
No
Inclusion criteria
* Signed informed consent prior to participation * Outpatients aged 19-64 years * Diagnosis of Major Depressive Disorder (MDD) per DSM-5 using MINI; psychotic features allowed * Current major depressive episode lasting ≥8 weeks at baseline * MADRS total score ≥24 at both screening and baseline * CGI-S score ≥4 at both screening and baseline * Documented history of antidepressant treatment (ADT) with inadequate response (\<50% improvement) * Currently on one of the protocol-permitted antidepressants at minimum effective dose for ≥6 weeks * Agreement to maintain the same background ADT regimen until study completion * BMI between 16-40 kg/m² * Willingness to discontinue prohibited psychotropic medications during washout * Stable doses of permitted concomitant medications (oral hypoglycemics ≥30 days, thyroid replacement ≥90 days, antihypertensives ≥30 days, lipid-lowering agents ≥30 days before baseline)
Exclusion criteria
* Lifetime diagnosis of schizophrenia, schizoaffective disorder, bipolar disorder, or other psychotic disorders * Diagnosis within past 6 months of panic disorder, generalized anxiety disorder, OCD, PTSD, eating disorder, substance abuse/dependence (except caffeine/nicotine), or clinically significant personality disorder * ≥25% reduction in MADRS score between screening and baseline * Significant suicide risk (per C-SSRS, MADRS item 10 ≥5, recent suicide attempt, or investigator judgment) * First major depressive episode onset after age 60 * Treatment resistance: ≥3 adequate ADT trials without remission, or non-response to antipsychotic augmentation * Prior ECT, VNS, rTMS within 5 years or history of ECT failure * Known hypersensitivity to lurasidone or excipients * Use of prohibited medications (strong CYP3A4 inhibitors/inducers, QTc-prolonging drugs) within 14 days before randomization * Prior exposure to lurasidone or investigational CNS drugs (per protocol limits) * Pregnancy, breastfeeding, or unwillingness to use effective contraception; positive pregnancy test at screening or baseline * Clinically significant ECG abnormalities. * Clinically significant laboratory abnormalities that may affect study participation or safety. * Clinically significant uncontrolled cardiovascular, hepatic, renal, endocrine, neurological, psychiatric, or other medical conditions that may affect study participation or safety. * Prolactin \>100 ng/mL or pituitary adenoma history * Investigator/site staff or family members of study personnel * Inability to comply with study procedures or anticipated relocation during study * More than 2 prior attempts at screening/washout for this study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Montgomery-Åsberg Depression Rating Scale Total Score at Week 8 | Baseline to Week 8 | The MADRS is a 10-item clinician-rated scale used to assess the severity of depressive symptoms. Each item is scored from 0 to 6, with a total score ranging from 0 to 60. Higher scores indicate greater severity of depressive symptoms. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Montgomery-Åsberg Depression Rating Scale Total Score by Lurasidone Dose (20, 40, or 60 mg) | Baseline to Week 8 | The Montgomery-Åsberg Depression Rating Scale (MADRS) is a 10-item clinician-rated scale used to assess the severity of depressive symptoms. Each item is scored from 0 to 6, resulting in a total score ranging from 0 to 60. Higher scores indicate greater severity of depressive symptoms. Mean change from baseline in MADRS total score at Week 8 will be evaluated for each lurasidone dose group (20, 40, or 60 mg) compared with placebo. |
| Change in Montgomery-Åsberg Depression Rating Scale Total Score During the Treatment Period by Lurasidone Dose (20, 40, or 60 mg) | dose-specific baseline to Week 8 | The Montgomery-Åsberg Depression Rating Scale (MADRS) is a 10-item clinician-rated scale used to assess the severity of depressive symptoms. Each item is scored from 0 to 6, resulting in a total score ranging from 0 to 60. Higher scores indicate greater severity of depressive symptoms. Mean change in MADRS total score during the treatment period will be evaluated for each lurasidone dose group (20, 40, or 60 mg) compared with placebo. |
| MADRS Response Rate | Baseline to Week 8 | The Montgomery-Åsberg Depression Rating Scale (MADRS) total score ranges from 0 to 60, with higher scores indicating greater severity of depressive symptoms. Response is defined as a change in MADRS total score from baseline that meets the prespecified criterion of at least a 50% decrease from baseline. |
| MADRS Remission Rate | Baseline to Week 8 | Proportion of participants with MADRS total score ≤10 at Week 8 |
| Change From Baseline in Clinical Global Impression-Severity Score | Baseline to Week 8 | Change from baseline in CGI-S score at Week 8. |
| Change From Baseline in Hamilton Anxiety Rating Scale Score | Baseline to Week 8 | Change from baseline in HAM-A score at Week 8. |
| Change From Baseline in 17-Item Hamilton Depression Rating Scale Score | Baseline to Week 8 | Change from baseline in HAM-D17 score at Week 8. |
| Change From Baseline in Sheehan Disability Scale Total and Subscale Scores | Baseline to Week 8 | Ｃhange from baseline in SDS total and subscale score at Week 8. |
Contacts
CONTACTHyunjeong Kim
CONTACTWonjun Seo
Outcome results
None listed