The study comprised 350 patients who were randomised to receive memantine monotherapy or placebo. Patients with MMSE scores between 5 and 14 were recruited, and baseline characteristics were similar between the memantine and placebo groups.

Ef?cacy assessments (ITT population) were made at Weeks 4, 8, 12, 18 and 24 (endpoint). The number of withdrawals was similar between the treatment groups, with 44 memantine patients (25%) discontinuing therapy in comparison with 46 placebo patients (27%).

        In the primary ef?cacy measures of function (ADCS-ADL₁₉) and cognition (SIB), the bene?t of memantine was not statistically signi?cant at endpoint, mainly due to a less than expected decline in the placebo group.

        SIB score was numerically in favour of memantine from Week 4, and reached statistical signi?cance at Week 12 (p=0.008, OC). Strong trends in favour of memantine were also seen at Weeks 8 (p=0.064, OC) and 18 (p=0.065, OC) (Figure 6.2).

        Due to violations of the normality assumptions for the SIB, nonparametric analyses were also performed. A statistically signi?cant bene?t of memantine over placebo was demonstrated for the SIB at all visits, including endpoint (OC and LOCF analyses).

        In the secondary ef?cacy measure of global status (CIBIC-Plus), memantine reached statistical signi?cance versus placebo at Weeks 12 (p=0.003, OC) and 18 (p=0.009, OC).

 

Although not statistically significant at endpoint, data from Study MD-01 support improvements in cognition and global status in memantine-treated patients with moderate to severe AD.

The study population comprised 404 patients (MMSE 5–14) already receiving stable treatment with donepezil. Eligible patients had been receiving donepezil therapy for at least 6 months, with no change of dose for the 3 months preceding the study, or during the study period. At the start of the study, patients were randomised to receive either memantine 20 mg/day or placebo.

Patients (ITT population) were assessed for ef?cacy at Weeks 4, 8, 12, 18, and 24. In total, 51 placebo patients (25%) withdrew from the study, in comparison with 30 patients (15%) from the memantine group. One patient in the memantine group withdrew prior to receiving any study medication, and was therefore excluded from the analysis.

        Memantine produced statistically signi?cant bene?ts versus placebo in all primary and secondary outcomes of global status, function, cognition and behaviour (Table 6.3).

        In addition, patients receiving memantine showed a sustained improvement over baseline in cognition (SIB score) versus placebo, over the 24-week study period.

        Improvement in behaviour (NPI score) was also maintained from Week 12 to endpoint in the memantine-treated patient group (Figure 6.3).³³

 

The study comprised 403 patients (MMSE 10–22) who were randomised to either memantine monotherapy (20 mg/day) or placebo. Baseline characteristics were similar between the memantine and placebo groups.

Primary and secondary outcome assessments of cognition, global patient status and activities of daily living were obtained at baseline and at the end of Weeks 4, 8, 12, 18, and 24 (endpoint), or at dropout. Secondary outcome assessments of behaviour were obtained at baseline and at the end of Weeks 12 and 24, or at dropout. All ef?cacy analyses were based on the ITT population.

The number of withdrawals was similar between the groups – 17% of the placebo-treated group and 18% of the memantinetreated group. The reasons for withdrawal were also generally similar between the groups.

        Memantine produced signi?cant improvements versus placebo at endpoint (Week 24; LOCF analysis), in the total mean scores of:

  global status: CIBIC-Plus (p=0.004; Figure 6.4)

  cognition: ADAS-Cog (p=0.003)

  behaviour: NPI (p=0.011).

            Memantine’s effect on functional outcome (ADCS-ADL₂₃) was not signi?cant (p=0.890).

 

The document about donepezil was translated by Huayiwang Mandarin Translation Company.

 

该研究入组了350名受试者，受试者随机进入美金刚单药组或者安慰剂组。入组的受试者MMSE评分为5-14分，美金刚组及安慰剂组基线特征相似。

在第4周、8周、12周、18周及24周（研究终点）时对受试者（ITT数据集）进行有效性评价，美金刚组及安慰剂组退出的受试者数目相似，美金刚组44名受试者（25%）中断治疗，安慰剂组46名受试者（27%）中断治疗。

         在患者功能的主要有效性评价(ADCS-ADL₁₉)及认知能力评价（SIB）方面，在研究终点时，美金刚组的受益较安慰剂组相比，无显著统计学意义，主要是因为安慰剂组受试者的恶化程度较预期低。

         从数字上看，美金刚组自第四周开始SIB评分即具有优势，在第12周具有统计学意义（p=0.008, OC）。美金刚能让受试者受益的强烈趋势也见于第8周（p=0.064， OC）及第18周（p=0.065， OC）（图 6.2）。

         由于SIB的数据不符合正态分布，采用非参数检验进行统计分析。在全部访视，包括观察终点，与安慰剂相比，美金刚能给受试者带来SIB方面的受益，具有显著统计学意义（OC 及 LOCF 分析）。

         在全身状况次要有效性评价（CIBIC-Plus）方面，在第12周及第18周，美金刚组与安慰剂组相比具有显著统计学意义，第12周（p=0.003， OC），第18周（p=0.009， OC）。

 

尽管在观察终点时没有显著统计学意义，MD-01的研究数据支持美金刚能改善中、重度阿尔茨海默病患者的认知能力及整体状况。

 

该研究入组了404名正在接受稳定剂量多奈哌齐治疗的受试者（MMSE 5-14）。合格的受试者至少接受了6个月的多奈哌齐治疗，并在参加该研究前的3个月内未改变剂量，或者在研究期间未改变剂量。在研究开始时，患者被随机分配至美金刚组（20毫克/天）或者安慰剂组。

在第4周、8周、12周、18周及24周时对受试者（ITT数据集）进行有效性评价。安慰剂组共51名受试者（25%）退出研究，美金刚组30名受试者（15%）退出研究。美金刚组一个受试者在接受任何研究药物前退出研究，因此排除在分析之外。

         在全身状况、功能、认知能力及行为所有主要及次要观察结果方面，美金刚组与安慰剂组相比均具有显著的统计学意义（表6.3）。

         另外，与安慰剂组相比，在为期24周的研究期间，美金刚组认知能力（SIB评分）较基线有持续的改善。

         在美金刚组，受试者行为能力（NPI评分）也得到改善，自第12周开始，一直维持到研究终点（图6.3）³³。

 

MD-10 (Peskind 等， 2006)²⁷

该研究入组了403名受试者（MMSE 10-22），受试者随机进入美金刚单药组（20毫克/天）或者安慰剂组。美金刚组及安慰剂组基线特征相似。

在基线、第4周、第8周、第12周、第18周及第24周（研究终点）或脱落时对受试者认知能力、整体状况及日常生活活动的主要及次要结果进行评价。在基线、第12周、第24周或者脱落时对受试者行为的次要结果进行评价。采用ITT数据集进行有效性分析。

安慰剂组退出的受试者比例为17%，美金刚组为18%，二者相似。两组之间受试者退出研究的理由也大致相似。

         在研究终点时（第24周；LOCF分析），与安慰剂组比较，美金刚组受试者的病情在下面总平均分方面出现极大改善：

  整体状况：CIBIC-Plus （p=0.004； 图 6.4）

  认知能力：ADAS-Cog （p=0.003）

  行为能力：NPI （p=0.011）。

            美金刚对功能性指标（ADCS-ADL₂₃）的效应不显著（p=0.890）。

原件下载：