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NCT Number: NCT07781293

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

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).

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Key information

Conditions

Major Depressive Disorder (MDD) Depressive Disorder Depressive Disorder, Major Major Depressive Disorder With Psychotic Features Mental Disorders Mood Disorders

Age range

19 year–64 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

About this study

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 19-65 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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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)

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 (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
  • 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

Treatment and study plan

Lurasidone

Drug

Lurasidone

Placebo

Drug

Placebo

Background Antidepressant Therapy

Drug

Background Antidepressant treatment (ADT)

Primary outcomes

  1. Change From Baseline in Montgomery-Åsberg Depression Rating Scale Total Score at Week 8

    Time frame: Baseline to Week 8

    The primary efficacy endpoint is the mean change from baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score at Week 8, comparing adjunctive lurasidone (20, 40, 60 mg/day) with placebo in adult patients with major depressive disorder who show inadequate response to antidepressant monotherapy.

    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.

Secondary outcomes

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

    Time frame: 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.

  2. Change in Montgomery-Åsberg Depression Rating Scale Total Score During the Treatment Period by Lurasidone Dose (20, 40, or 60 mg)

    Time frame: 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.

  3. MADRS Response Rate

    Time frame: 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.

  4. MADRS Remission Rate

    Time frame: Baseline to Week 8

    Proportion of participants with MADRS total score ≤10 at Week 8

  5. Change From Baseline in Clinical Global Impression-Severity Score

    Time frame: Baseline to Week 8

    The Clinical Global Impression-Severity (CGI-S) scale is a clinician-rated measure of overall illness severity. Scores range from 1 to 7, with higher scores indicating greater illness severity. The outcome measure is the mean change in Clinical Global Impression-Severity score compared to placebo.

  6. Change From Baseline in Hamilton Anxiety Rating Scale Score

    Time frame: Baseline to Week 8

    The Hamilton Anxiety Rating Scale (HAM-A) is a 14-item clinician-rated scale used to assess the severity of anxiety symptoms. Each item is scored from 0 to 4, resulting in a total score ranging from 0 to 56. Higher scores indicate greater severity of anxiety symptoms. The outcome measure is the mean change in Hamilton Anxiety Rating Scale score compared to placebo.

  7. Change From Baseline in 17-Item Hamilton Depression Rating Scale Score

    Time frame: Baseline to Week 8

    The 17-item Hamilton Depression Rating Scale (HAM-D17) is a clinician-rated scale used to assess the severity of depressive symptoms. The total score ranges from 0 to 52, with higher scores indicating greater severity of depressive symptoms. The outcome measure is the mean change in Hamilton Depression Rating Scale (17-item) score compared to placebo.

  8. Change From Baseline in Sheehan Disability Scale Total and Subscale Scores

    Time frame: Baseline to Week 8

    The Sheehan Disability Scale (SDS) is a 3-item self-rated scale that assesses functional impairment in work or school, social life, and family life or home responsibilities. Each domain is scored from 0 to 10, with higher scores indicating greater functional impairment. The total score ranges from 0 to 30, with higher scores indicating greater overall functional impairment. Changes from baseline in the SDS total and subscale scores will be evaluated compared with placebo.

Other outcomes

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

    Time frame: Baseline ~ Week8 + 1week Safety Follow-up

    Frequency and proportion of participants experiencing adverse events, serious adverse events, and discontinuations due to adverse events during the study.

  2. Change From Baseline in Abnormal Involuntary Movement Scale Total Score

    Time frame: Baseline ~ Week8 + 1week Safety Follow-up

    The Abnormal Involuntary Movement Scale (AIMS) is a clinician-rated scale used to assess the severity of abnormal involuntary movements. Items assessing abnormal movements are rated from 0 (none) to 4 (severe), with higher scores indicating greater severity of abnormal involuntary movements. Change from baseline in the AIMS total score will be evaluated.

  3. Change From Baseline in Barnes Akathisia Rating Scale Total Score

    Time frame: Baseline ~ Week8 + 1week Safety Follow-up

    The Barnes Akathisia Rating Scale (BARS) is a clinician-rated scale used to assess akathisia. The scale includes objective restlessness, subjective awareness of restlessness, subjective distress related to restlessness, and a global clinical assessment of akathisia. Higher scores indicate greater severity of akathisia. Change from baseline in the BARS total score will be evaluated.

  4. Change From Baseline in Simpson-Angus Scale Total Score

    Time frame: Baseline ~ Week8 + 1week Safety Follow-up

    The Simpson-Angus Scale (SAS) is a 10-item clinician-rated scale used to assess drug-induced parkinsonian symptoms. Each item is scored from 0 to 4, with higher scores indicating greater severity of parkinsonian symptoms. The total score ranges from 0 to 40. Change from baseline in the SAS total score will be evaluated.

  5. Number of Participants With Clinically Significant Abnormal Clinical Laboratory Findings

    Time frame: Baseline ~ Week8 + 1week Safety Follow-up

    The number and percentage of participants with at least one protocol-specified clinical laboratory finding assessed by the investigator as clinically significant will be summarized.

  6. Number of Participants With Clinically Significant Abnormal Physical Examination Findings

    Time frame: Baseline ~ Week8 + 1week Safety Follow-up

    The number and percentage of participants with at least one clinically significant abnormal finding identified during a protocol-specified physical examination will be summarized.

  7. Change From Baseline in Body Weight

    Time frame: Baseline ~ Week8 + 1week Safety Follow-up

    Change from baseline in body weight measured in kilograms.

  8. Change From Baseline in Waist Circumference

    Time frame: Baseline ~ Week8 + 1week Safety Follow-up

    Change from baseline in waist circumference measured in centimeters.

  9. Change From Baseline in Seated Systolic Blood Pressure

    Time frame: Baseline ~ Week8 + 1week Safety Follow-up

    Change from baseline in seated systolic blood pressure measured in millimeters of mercury (mmHg).

  10. Change From Baseline in Seated Diastolic Blood Pressure

    Time frame: Baseline ~ Week8 + 1week Safety Follow-up

    Change from baseline in seated diastolic blood pressure measured in millimeters of mercury (mmHg).

  11. Change From Baseline in Pulse Rate

    Time frame: Baseline ~ Week8 + 1week Safety Follow-up

    Change from baseline in pulse rate measured in beats per minute.

  12. Change From Baseline in Body Temperature

    Time frame: Baseline ~ Week8 + 1week Safety Follow-up

    Change from baseline in body temperature measured in degrees Celsius.

  13. Change From Baseline in Electrocardiogram Heart Rate

    Time frame: Baseline ~ Week8 + 1week Safety Follow-up

    Change from baseline in heart rate measured by standard 12-lead electrocardiogram, reported in beats per minute.

  14. Change From Baseline in RR Interval

    Time frame: Baseline ~ Week8 + 1week Safety Follow-up

    Change from baseline in RR interval measured by standard 12-lead electrocardiogram, reported in milliseconds.

  15. Change From Baseline in PR Interval

    Time frame: Baseline ~ Week8 + 1week Safety Follow-up

    Change from baseline in PR interval measured by standard 12-lead electrocardiogram, reported in milliseconds.

  16. Change From Baseline in QT Interval

    Time frame: Baseline ~ Week8 + 1week Safety Follow-up

    Change from baseline in QT interval measured by standard 12-lead electrocardiogram, reported in milliseconds.

  17. Change From Baseline in QRS Duration

    Time frame: Baseline ~ Week8 + 1week Safety Follow-up

    Change from baseline in QRS duration measured by standard 12-lead electrocardiogram, reported in milliseconds.

  18. Change From Baseline in Bazett-Corrected QT Interval

    Time frame: Baseline ~ Week8 + 1week Safety Follow-up

    Change from baseline in QT interval corrected for heart rate using the Bazett formula (QTcB), reported in milliseconds.

  19. Suicidal Ideation and Suicidal Behavior Assessed by the Columbia-Suicide Severity Rating Scale

    Time frame: Baseline ~ Week8 + 1week Safety Follow-up

    The Columbia-Suicide Severity Rating Scale (C-SSRS) is a clinician-administered assessment used to identify and classify suicidal ideation and suicidal behavior. This outcome measure does not report a single C-SSRS total score. The frequency and percentage of participants with protocol-specified categories of suicidal ideation and suicidal behavior will be summarized.

Study contacts

Contact information is provided by the study sponsor or research team.

Wonjun Seo

CONTACT

[email protected]

+82-2-828-8161

Yeram An

CONTACT

[email protected]

+82-2-828-8204

Sponsors and collaborators

Lead sponsor

Bukwang Pharmaceutical

Industry

Registry information

Official study title

Evaluating the Efficacy and Safety of Lurasidone as Adjunctive Therapy in Adult Patients Diagnosed With Major Depressive Disorder Who Have an Inadequate Response to Antidepressant Monotherapy: A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Trial

Important dates

Study start
2026
Primary completion
2027
Study completion
2027
First posted
Aug 24, 2026
Registry last updated
Aug 24, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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