Study of Lurasidone as Adjunctive Treatment in Patients With Major Depressive Disorder With Inadequate Response to Antidepressant Monotherapy

NCT07781293 | Not Yet Recruiting Phase 3

• 1 other identifier: BK-LUD-302
• Study Type: interventional
• Target: 364
• Locations: 0 countries
• Sites: N/A

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).

Conditions

Major Depressive Disorder (MDD); Major Depressive Disorder With Psychotic Features

Keywords

Major Depressive Disorder; Antidepressant Inadequate Response; Adjunctive Therapy; Randomized Double-Blind Placebo-Controlled

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Montgomery-Åsberg Depression Rating Scale Total Score at 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.

  Baseline to Week 8

Secondary Outcomes (8)

• Change From Baseline in Montgomery-Åsberg Depression Rating Scale Total Score by Lurasidone Dose (20, 40, or 60 mg)

  Baseline to Week 8

• 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

• MADRS Response Rate

  Baseline to Week 8

• MADRS Remission Rate

  Baseline to Week 8

• Change From Baseline in Clinical Global Impression-Severity Score

  Baseline to Week 8

Other Outcomes (19)

• Incidence of Adverse Events (AE), Serious Adverse Events (SAE), and Discontinuations due to AE

  Baseline ~ Week8 + 1week Safety Follow-up

• Change From Baseline in Abnormal Involuntary Movement Scale Total Score

  Baseline ~ Week8 + 1week Safety Follow-up

• Change From Baseline in Barnes Akathisia Rating Scale Total Score

  Baseline ~ Week8 + 1week Safety Follow-up

Study Arms (2)

Lurasidone + Antidepressant

EXPERIMENTAL

Drug: Lurasidone; Drug: Background Antidepressant Therapy

Placebo + Antidepressant

PLACEBO COMPARATOR

Drug: Placebo; Drug: Background Antidepressant Therapy

Interventions

Lurasidone DRUG

Lurasidone

Lurasidone + Antidepressant

Placebo DRUG

Placebo

Placebo + Antidepressant

Background Antidepressant Therapy DRUG

Background Antidepressant treatment (ADT)

Lurasidone + Antidepressant; Placebo + Antidepressant

Eligibility Criteria

• Age: 19 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Signed informed consent prior to participation
• Outpatients aged 19-65 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), confirmed by ATRQ
• Currently on one of the allowed antidepressants (SSRI: citalopram, escitalopram, fluoxetine, paroxetine, sertraline; SNRI: duloxetine, venlafaxine, desvenlafaxine, milnacipran; Others: bupropion, vortioxetine, amitriptyline, tianeptine, agomelatine) 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)

You may not qualify if:

• 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 (QTcB ≥460 ms in men, ≥480 ms in women)
• Clinically significant lab abnormalities: ALT/AST \>2× ULN, bilirubin \>1.5× ULN, Hb \<8 g/dL (women) or \<9 g/dL (men), ANC \<1,200/µL, HbA1c \>8%, HBsAg or HCV antibody positive (unless HCV RNA negative), CrCl \<50 mL/min, abnormal thyroid function (TSH, free T3/T4)
• History of serious medical conditions: uncontrolled cardiovascular disease, recent MI, arrhythmia, active cancer (within 5 years, except basal/squamous cell skin cancer), GI surgery affecting absorption, uncontrolled endocrine disease, moderate/severe hepatic impairment, untreated sleep apnea, seizure disorders, dementia, HIV infection
• Prolactin \>100 ng/mL or pituitary adenoma history

Sponsors & Collaborators

• Bukwang Pharmaceutical: lead

Related Links

• Nedrug(MFDS)

MeSH Terms

Conditions

Depressive Disorder, Major

Interventions

Lurasidone Hydrochloride

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Central Study Contacts

Yeram An

CONTACT

+82-2-828-8204; ye.ram.an@bukwang.co.kr

Wonjun Seo

CONTACT

+82-2-828-8161; won.jun.seo@bukwang.co.kr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: August 6, 2026
• First Posted: August 24, 2026
• Study Start (Estimated): September 28, 2026
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): October 1, 2027
• Last Updated: August 27, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will not share