A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-arm Study to Assess the Efficacy, Safety, and Tolerability of AVP-786 (Deudextromethorphan Hydrobromide [d6-DM]/Quinidine Sulfate [Q]) for the Treatment of Negative Symptoms of Schizophrenia
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 136
- 试验地点
- 132
- 主要终点
- Change From Baseline (Week 3) to Week 15 in the Positive and Negative Syndrome Scale (PANSS) Marder Negative Factors Score
研究概览
简要总结
This study was conducted to evaluate the efficacy, safety, and tolerability of AVP-786, as compared with placebo, for the treatment of negative symptoms of schizophrenia.
研究设计
- 研究类型
- 干预性
- 分配方式
- 随机
- 干预模型
- 平行分组
- 主要目的
- 治疗
- 盲法
- 四盲 (受试者、医护人员、研究者、结局评估者)
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- Participants who meet the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-V) diagnostic criteria for schizophrenia confirmed by the Mini International Neuropsychiatric Interview (M.I.N.I) Version 7.0.2
- Participants must have well-controlled positive symptoms and prominent negative symptoms as defined by Positive and Negative Syndrome Scale (PANSS) criteria.
- Participants currently receiving a second-generation atypical antipsychotic drug (SGA) are eligible if they are stable and adherent to their dosing schedule.
- Participants must have a reliable informant (e.g., case manager, social worker, family member). The informant should be able to spend an adequate amount of time with the participant to be able to address behaviors, activities, and symptoms.
排除标准
- Participants with current major depressive disorder (MDD)
- Participants with pseudo-parkinsonism secondary to their ongoing antipsychotic medication
- Participants currently using anticholinergic medications
- Participants recently hospitalized as in-patients
研究组 & 干预措施
Placebo
Participants received AVP-786 matching placebo capsules, orally, BID over a 12-week DBT period.
干预措施: Placebo (Drug)
AVP-786
Participants received AVP-786-28/4.9 (deudextromethorphan hydrobromide (d6-DM) 28 milligrams (mg)/quinidine sulfate (Q) 4.9 mg) capsule, along with AVP-786 matching placebo capsule, orally, once daily (QD) for 3 days followed by AVP-786-28/4.9 capsule, orally, BID for the next 4 days of titration period. Following the 1-week titration period, participants received AVP-786-42.63/4.9 (d6-DM 42.63 mg/Q 4.9 mg), orally, BID for the remaining 11 weeks of the DBT period.
干预措施: AVP-786 (Drug)
Placebo (Run-in Period)
Participants received AVP-786 matching placebo capsules, orally, twice a day (BID) over a 3-week run-in period.
干预措施: Placebo (Drug)
方案终点
主要结局
Change From Baseline (Week 3) to Week 15 in the Positive and Negative Syndrome Scale (PANSS) Marder Negative Factors Score
时间窗: Baseline (Week 3); Week 15
The PANSS is a validated clinical scale used as a reliable and valid measure of the negative and positive symptom of schizophrenia. PANSS consists of three subscales: a total of 30 disparate items. Each item's severity was rated on a 7-point scale, with a score of 1 (absence of symptoms) and a score of 7 (extremely severe symptoms). The PANSS marder negative factors score is comprised of the following 7 items of the 30-item PANSS: blunted affect, emotional withdrawal, poor rapport, passive/apathetic social withdrawal, lack of spontaneity and flow of conversation, motor retardation and active social avoidance. The PANSS Negative Subscale ranges from 7 (absence of symptoms) to 49 (extremely severe symptoms). PANSS total score range is 30 to 210, with higher scores indicating more severe symptoms. Negative change from baseline indicates improvement. Baseline is defined as the end of the placebo run-in period (Week 3), and to be the last assessment prior to the first dose of study drug.
Change from Baseline to Week 15 in the Positive and Negative Syndrome Scale (PANSS) Marder Negative Factors Score
时间窗: Baseline; Week 15
次要结局
- Change From Baseline (Week 3) to Week 15 in the Negative Symptom Assessment-16 (NSA-16) Global Negative Symptom Score(Baseline (Week 3); Week 15)
- Change From Baseline (Week 3) to Week 15 in the Patient Global Impression of Severity (PGI-S) Score(Baseline (Week 3); Week 15)
- Patient Global Impression of Change (PGI-C) Score(At Weeks 6, 9, 12 and 15)
- Change from Baseline to Week 15 in the Negative Symptom Assessment-16 (NSA-16) Global Negative Symptom Score(Baseline; Week 15)
- Change from Baseline to Week 15 in the Patient Global Impression of Severity (PGI-S) Score(Baseline; Week 15)
- Change from Baseline to Week 15 in the Patient Global Impression of Change (PGI-C) Score(Baseline; Week 15)
试验结果
结果已于 2026-09-29 在 ClinicalTrials.gov 公示。 在 ClinicalTrials.gov 查看
受试者流程
入组 136 人 · 完成 109 人
主要终点
Change From Baseline (Week 3) to Week 15 in the Positive and Negative Syndrome Scale (PANSS) Marder Negative Factors Score
score on a scale · Standard Error · 时间窗: Baseline (Week 3); Week 15
| AVP-786 （n=61） | Placebo （n=54） |
|---|---|
| -2.3 (0.47) | -2.5 (0.49) |
mITT population included all participants who were placebo run-in nonresponders, randomized in Phase B and in the safety population with both Phase B baseline and at least 1 postbaseline PANSS measurement.
Least Squares (LS) Mean Difference 0.2 · 95% 置信区间 -1.09–1.47 · p = 0.768 · MMRM
The mixed-effects model for repeated measures (MMRM) analysis included fixed effects for treatment, trial center, visit, treatment-by-visit interaction, and baseline-by-visit interaction. An unstructured covariance model was used.
其他终点（3）
Change From Baseline (Week 3) to Week 15 in the Negative Symptom Assessment-16 (NSA-16) Global Negative Symptom Score
score on a scale · Standard Error · 时间窗: Baseline (Week 3); Week 15
| AVP-786 （n=61） | Placebo （n=54） |
|---|---|
| -0.4 (0.10) | -0.5 (0.10) |
mITT population included all participants who were placebo run-in nonresponders, randomized in Phase B and in the safety population with both Phase B baseline and at least 1 postbaseline PANSS measurement.
LS Mean Difference 0.1 · 95% 置信区间 -0.17–0.37 · p = 0.443 · MMRM
The MMRM analysis included fixed effects for treatment, trial center, visit, treatment-by-visit interaction, and baseline-by-visit interaction. An unstructured covariance model was used.
Change From Baseline (Week 3) to Week 15 in the Patient Global Impression of Severity (PGI-S) Score
score on a scale · Standard Error · 时间窗: Baseline (Week 3); Week 15
| AVP-786 （n=61） | Placebo （n=54） |
|---|---|
| -0.3 (0.16) | -0.4 (0.16) |
mITT population included all participants who were placebo run-in nonresponders, randomized in Phase B and in the safety population with both Phase B baseline and at least 1 postbaseline PANSS measurement.
LS Mean Difference 0.1 · 95% 置信区间 -0.31–0.54 · p = 0.590 · MMRM
The MMRM analysis included fixed effects for treatment, trial center, visit, treatment-by-visit interaction, and baseline-by-visit interaction. An unstructured covariance model was used.
Patient Global Impression of Change (PGI-C) Score
score on a scale · Standard Deviation · 时间窗: At Weeks 6, 9, 12 and 15
| 分类 | AVP-786 （n=61） | Placebo （n=54） |
|---|---|---|
| Week 6 | 3.1 (1.07) | 3.0 (1.05) |
| Week 9 | 2.8 (1.10) | 2.9 (0.98) |
| Week 12 | 2.9 (1.15) | 2.9 (1.05) |
| Week 15 | 2.8 (1.20) | 2.9 (1.00) |
mITT population included all participants who were placebo run-in nonresponders, randomized in Phase B and in the safety population with both Phase B baseline and at least 1 postbaseline PANSS measurement.
Treatment Difference 0.1 · 95% 置信区间 -0.31–0.51 · p = 0.6377 · Cochran-Mantel-Haenszel
P-value and treatment difference (CI) were derived from Cochran-Mantel-Haenszel (CMH) row mean scores statistics controlling for study center.
Treatment Difference -0.1 · 95% 置信区间 -0.51–0.24 · p = 0.4827 · Cochran-Mantel-Haenszel
P-value and treatment difference (CI) were derived from CMH row mean scores statistics controlling for study center.
Treatment Difference 0.0 · 95% 置信区间 -0.43–0.36 · p = 0.8662 · Cochran-Mantel-Haenszel
P-value and treatment difference (CI) were derived from CMH row mean scores statistics controlling for study center.
Treatment Difference -0.1 · 95% 置信区间 -0.51–0.30 · p = 0.6062 · Cochran-Mantel-Haenszel
P-value and treatment difference (CI) were derived from CMH row mean scores statistics controlling for study center.
安全性
| 组别 | 严重不良事件 | 死亡 |
|---|---|---|
| Placebo (Run-in Period) | 0 / 136 | 0 / 136 |
| AVP-786 | 2 / 65 | 0 / 65 |
| Placebo | 0 / 60 | 0 / 60 |
最常见的严重不良事件（人数）
| 事件 | Placebo (Run-in Period) | AVP-786 | Placebo |
|---|---|---|---|
| Cellulitis | 0 / 136 | 1 / 65 | 0 / 60 |
| Pneumonia | 0 / 136 | 1 / 65 | 0 / 60 |
数值为申办方在 ClinicalTrials.gov 公示的原始数据，未经重新计算；括号内为公示的离散度（如 95% 置信区间）。
研究者
研究点 (132)
标识符
- NCT 编号
- NCT03896945
- 其他研究编号
- 18-AVP-786-207, 2021-001352-33
日期
- 首次提交
- (7年前)
- 首次发布
- (7年前)
- 主要完成日期
- (3年前)
- 研究完成日期
- (3年前)
- 最近核实
- (29天前)
- 最近更新
- (昨天)
监管与共享
- FDA 监管药物
- 是
- FDA 监管器械
- 否
- 个体参与者数据共享计划
- 是
- 是否有结果
- 是
Anonymized Individual participant data (IPD) that underlie the results of this study will be shared with researchers to achieve aims pre-specified in a methodologically sound research proposal. Small studies with less than 25 participants are excluded from data sharing.