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
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 364
- 主要终点
- Change From Baseline in Montgomery-Åsberg Depression Rating Scale Total Score at Week 8
研究概览
简要总结
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).
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
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.
入排标准
- 年龄范围
- 19 Years 至 64 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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)
排除标准
- •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
研究组 & 干预措施
Lurasidone + Antidepressant
干预措施: Background Antidepressant Therapy (Drug)
Placebo + Antidepressant
干预措施: Placebo (Drug)
Placebo + Antidepressant
干预措施: Background Antidepressant Therapy (Drug)
Lurasidone + Antidepressant
干预措施: Lurasidone (Drug)
结局指标
主要结局
Change From Baseline in Montgomery-Åsberg Depression Rating Scale Total Score at Week 8
时间窗: 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.
次要结局
- 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)(Baseline to Week 8)
- MADRS Response Rate(Baseline to Week 8)
- MADRS Remission Rate(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)
- Change From Baseline in Sheehan Disability Scale Total and Subscale Scores(Baseline to Week 8)
- Change From Baseline in Clinical Global Impression-Severity Score(Baseline to Week 8)
- Change From Baseline in Hamilton Anxiety Rating Scale Score(Baseline to Week 8)
- Change From Baseline in 17-Item Hamilton Depression Rating Scale Score(Baseline to Week 8)