Following on from the 28-week, double-blind phase of study MRZ-9605, 175 ‘completers’ (memantine or placebo) were re-titrated and continued on open-label memantine (20 mg/day) for a further 24 weeks. Patients remained blinded to their initial 28-week treatment.

In the double-blind phase, patients who took memantine declined at a signi?cantly slower rate than those who took placebo.10 In the long-term analysis, ef?cacy measures assessed the rate of decline in patients over the whole 52-week period, in the domains of global status, function and cognition.

      The rate of decline in patients in the former placebo group slowed signi?cantly upon their switch to memantine in the extension phase – the change in rate of decline was statistically signi?cant in all three domains (Figure 6.18).

      The rate of decline in patients who received memantine in both phases of the study varied across ef?cacy measures. Comparing outcome in the open-label phase with the double-blind phase, the rate of global decline decreased signi?cantly (p<0.001, OC analysis), the rate of cognitive decline remained unchanged, and the rate of functional decline increased (Figure 6.19).

 

The 148-week extension of study Lu-99679 assessed the decline/rate of disease progression of patients treated with memantine compared to untreated patients, and TEAEs between groups.

Completers of the 24-week, randomised, double-blind, placebo-controlled, 6-month lead-in study Lu-99679 (baseline MMSE 11–23, inclusive – mild to moderate AD) were enrolled in this extension study.

Patients who had received memantine 20 mg/day in the lead-in study continued the same treatment for up to an additional 148 weeks. Those who had received placebo in study Lu-99679 were titrated up to 20 mg/day memantine over 3 weeks, followed by up to 145 weeks of maintenance treatment.

The ADAS-Cog scale was used to assess decline, and in order to assess decline against longitudinal studies in AD patients. Adverse events were also recorded.

      Patients receiving long-term memantine treatment showed less decline (approximately 4.5 points per year) on the ADAS-Cog than longitudinal studies have shown for AD patients not receiving any treatment (approximately 9–11 points per year) – Figure 6.20.60,61

      Memantine-treated patients showed a decreased rate of disease progression on the ADAS-Cog scale during the 3-year extension study, providing further support to other studies into the long-term effects of AD therapies.

      Initiation of memantine treatment did not cause any major increases in TEAEs in the patients who had received placebo in the lead-in study.

 

We translated the file about Long-term extension from English into Chinese.

 

MRZ-9605 为期28周的双盲研究结束后，175名“完成试验者”（美金刚组或者安慰剂组）被再次滴定并继续24周开放的美金刚研究（每天20mg）。患者在最初的28周治疗期保持盲态。

在双盲期，美金刚组患者的恶化速度明显慢于安慰剂组10。在长期有效性分析中，有效性评价方法评价了患者52周期间的恶化程度，评价指标涉及整体状况、功能及认知能力。

     在扩展期，前面服用安慰剂的患者改为服用美金刚后，患者的恶化程度明显减慢，在整体状况、功能及认知能力三个域方面恶化程度的变化均有显著统计学意义（图6.18）。

     在研究的双盲期及开放期，接受美金刚治疗的患者有效性评价指标的恶化程度有所不同。开放期与双盲期比较，整体状况恶化程度减缓比较明显（p<0.001，OC分析），认知能力的恶化情况保持不变，功能恶化情况加速（图6.19）。

 

Lu-99679为期148周的扩展研究评价了美金刚治疗组与安慰剂组之间疾病的恶化情况/疾病进展情况，以及各组之间治疗出现的不良事件（TEAEs）情况

完成24周随机、双盲、安慰剂对照、6个月导入期研究Lu-99679（基线MMSE 11-23，入选标准为轻、中度AD患者）的受试者被入选到该扩展研究中。

在导入期接受每天20mg剂量美金刚治疗的患者继续相同的治疗，直至完成另一个148周治疗周期。在Lu-99679研究中接受安慰剂治疗的患者则在扩展研究的3周滴定期内将美金刚的剂量滴定到20mg/天，随后完成145周的美金刚维持治疗。

为了与纵向研究中患者的恶化情况比较，采用ADAS-Cog量表评价患者的恶化情况。同时记录患者所发生的不良事件。

     与纵向研究中未接受任何治疗的AD患者（大约每年9-11分）相比，接受长期美金刚治疗的患者在ADAS-Cog评分方面恶化速度减缓（大约每年4.5分） – 图6.2060,61

     在为期3年的扩展研究中，美金刚治疗组在ADAS-Cog 量表方面疾病进展的速度减慢，为其他美金刚治疗AD患者长期效果的研究提供了进一步的支持。

     在导入研究中，安慰剂组的患者接受美金刚治疗后并未导致任何治疗出现的不良事件（TEAEs）出现大的增加。

 

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