A Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy, Safety, and Tolerability of AVP-786 (Deuterium Modified Dextromethorphan Hydrobromide/Quinidine Sulfate) as an Adjunctive Therapy in Patients With Major Depressive Disorder With an Inadequate Response to Antidepressant Treatment
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 206
- 试验地点
- 32
- 主要终点
- Montgomery-Ǻsberg Depression Rating Scale (MADRS) total score
研究概览
简要总结
The objectives of this 10-week study are to evaluate the efficacy, safety, and tolerability of AVP 786 as an adjunctive therapy compared with placebo in patients with major depressive disorder (MDD) who have shown an inadequate response to standard antidepressant treatment. A secondary objective of this study is to assess the pharmacokinetics (PK) of AVP-786 and potential correlations with pharmacodynamic effects.
详细描述
It is estimated that up to approximately 200 patients will participate in the study at approximately 30 enrolling centers in the US.
Eligible patients for this study must have MDD as defined by the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) criteria, and have shown an inadequate response to standard antidepressant treatment.
This is a multicenter, randomized, double-blind, placebo-controlled, study of 10 weeks duration.
Following screening procedures for assessment of inclusion and exclusion criteria, eligible patients will be randomized into the study. Study medication will be administered orally twice a day (BID) (1 capsule in the morning and 1 capsule in the evening, approximately 12 hours apart) throughout the treatment period.
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)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Clinical diagnosis of major depressive episode ≤ 24 months in duration
- •HAM-D17 score ≥
- •Documented to not have a significant (25% or greater) change in QIDS-SR16 score between Screening and Baseline visits.
- •Patients have been deemed to have an inadequate response (less than 50% symptom reduction) to at least 1 but no more than 3 adequate antidepressant trials during the current depressive episode.
- •Patients must be receiving ongoing treatment with an adequate dose of antidepressants.
- •Body Mass Index (BMI) of 18-35 kg/m².
排除标准
- •History of myasthenia gravis.
- •Have cardiovascular concerns such as:
- •History of complete heart block, QT interval corrected for heart rate (QTc) prolongation, or torsades de pointes.
- •QTc using the Fridericia's formula (QTcF) at screening > 450 msec for males and > 470 msec for females based on central review at the screening visit, unless due to ventricular pacing.
- •Any family history of congenital QT interval prolongation syndrome.
- •Known hypersensitivity/intolerance to DM, Q, opiate drugs (codeine, etc.), or any other ingredient of the study medication.
- •Pose a current suicide risk, as evidenced by any of the following:
- •It is the judgment of the investigator that the subject may be at risk for suicide.
- •The subject is rated a "yes" to question 4 or question 5 on the Baseline C-SSRS, if the most recent episode occurred within the past 12 months.
- •The subject has attempted suicide within the past 6 months
- •Presence of any other current DSM-IV-TR Axis I disorders with the exception of: generalized anxiety disorder (GAD: 300.02), social anxiety disorder (300.23), dysthymic disorder (300.4), or specific phobia (300.29). Patients with co-morbid GAD, social anxiety disorder, or specific phobia are ineligible if the co-morbid condition is clinically unstable, or has been the primary focus of treatment within the 6 month period prior to screening
- •Axis I diagnosis of:
- •Delirium, dementia, amnestic, or other cognitive disorder;
- •Schizophrenia or other psychotic disorder, based on the M.I.N.I.;
- •Bipolar I or II disorder, based on the M.I.N.I.
- •Clinically significant Axis II (DSM-IV-TR) diagnosis of borderline, antisocial, paranoid, schizoid, schizotypal or histrionic personality disorder.
研究组 & 干预措施
AVP-786
干预措施: AVP-786 (d6-dextromethorphan hydrobromide and quinidine sulfate combination) (Drug)
Placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Montgomery-Ǻsberg Depression Rating Scale (MADRS) total score
时间窗: Visit 5 (Day 70) Week 10
The MADRS consists of 10 items, each rated based on the structured interview. The dimensions assessed in the MADRS are as follows: 1. Apparent sadness 2. Reported sadness 3. Inner tension 4. Reduced sleep 5. Reduced appetite 6. Concentration difficulties 7. Lassitude 8. Inability to feel 9. Pessimistic thoughts 10. Suicidal thoughts. Each item is rated on a scale from 0 to 6. The MADRS total score is the sum of the scores for the 10 dimensions and can range from 0 to 60, with higher scores indicating a higher severity of depression.
次要结局
- Sheehan Disability Scale (SDS)(Visit 5 (Day 70) Week 10)
- 17-item Hamilton Rating Scale for Depression (HAM-D17)(Visit 5 (Day 70) Week 10)
- Massachusetts General Hospital Antidepressant Treatment Response Questionnaire (MGH ATRQ)(Visit 5 (Day 70) Week 10)
- 16-item Quick Inventory of Depressive Symptomatology - Self Report (QIDS-SR16)(Visit 5 (Day 70) Week 10)
- Clinical Global Impression of Severity of Illness (CGI-S)(Visit 5 (Day 70) Week 10)
- Clinical Global Impression of Change (CGI-C)(Visit 5 (Day 70) Week 10)
- EuroQOL 5 Dimension 5 Level (EQ-5D-5L)(Visit 5 (Day 70) Week 10)
- Patient Global Impression of Change (PGIC)(Visit 5 (Day 70) Week 10)
- 7-item Generalized Anxiety Disorder (GAD-7)(Visit 5 (Day 70) Week 10)