Open-Label Extension for Alzheimer's Disease Patients Who Complete One of Two Semagacestat Phase 3 Double-Blind Studies (H6L-MC-LFAN or H6L-MC-LFBC)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 180
- 试验地点
- 1
- 主要终点
- Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog11) at Week 16 After Cessation of Study Drug
研究概览
简要总结
The primary objective of the original study was to assess the safety of semagacestat in Alzheimer's disease (AD) patients during 24 months of open-label treatment. Baseline for the efficacy measures is defined as the baseline for feeder studies LFAN (NCT00594568) and LFBC (NCT00762411). For all safety analyses (adverse events), baseline for patients will be week 0 of this study (LFBF).
Preliminary results from LFAN and LFBC showed semagacestat did not slow disease progression and was associated with worsening of clinical measures of cognition and the ability to perform activities of daily living. Study drug was stopped in all studies. Studies LFAN, LFBC and LFBF have been amended to continue collecting safety data, including cognitive scores, for at least seven months. The CT-Registry will reflect results of analyses from the original protocol in addition to those from the amended protocol. Very few participants from LFBC rolled over into LFBF (N = 9). Due to insufficient sample size, the data for LFBC participants who rolled into LFBF were not analyzed.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 55 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Meets National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS/ADRDA) criteria for probable Alzheimer's Disease
- •Completed semagacestat study LFAN or study LFBC through 88 weeks
- •Must continue to have a reliable caregiver
- •Capable of swallowing whole oral medication
- •Agrees not to participate in other investigational compounds for the duration of study
排除标准
- •Meets LFAN or LFBC study discontinuation criteria at the last visit of the LFAN or LFBC study
研究组 & 干预措施
Drug: semagacestat
干预措施: semagacestat (Drug)
结局指标
主要结局
Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog11) at Week 16 After Cessation of Study Drug
时间窗: Baseline (LFAN randomization), 16 weeks (LFBF) after cessation of study drug
The cognitive subscale of the ADAS (ADAS-Cog11) consists of 11 items assessing areas of function most typically impaired in Alzheimer's Disease (AD): orientation, verbal memory, language, and praxis. The scale ranges from 0 to 70, with higher scores indicating greater disease severity.
Change From Baseline in Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory (ADCS-ADL) at Week 16 After Cessation of Study Drug
时间窗: Baseline (LFAN randomization), 16 weeks (LFBF) after cessation of study drug
The ADCS-ADL is a 23-item inventory developed as a rater-administered questionnaire answered by the participant's caregiver. It measures both basic and instrumental activities of daily living. The total score ranges from 0 to 78, with lower scores indicating greater disease severity.
次要结局
- Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog14) at Week 12(Baseline (LFAN Randomization), 12 weeks (LFBF))
- Change From Baseline in Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory (ADCS-ADL) at Week 12(Baseline (LFAN Randomization), 12 weeks (LFBF))
- Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog14) at Week 16 After Cessation of Study Drug(Baseline (LFAN Randomization), 16 weeks (LFBF) after cessation of study drug)
- Change From Baseline in Neuropsychiatric Inventory (NPI) at Week 24(Baseline (LFAN Randomization), 24 weeks (LFBF))
- Change From Baseline in Hippocampal Volume Using Volumetric Magnetic Resonance Imaging (vMRI) at Week 12(Baseline (LFAN Randomization), 12 weeks (LFBF))
- Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog12) at Week 16 After Cessation of Study Drug(Baseline (LFAN Randomization), 16 weeks (LFBF) after cessation of study drug)
- Percent Change From Baseline in Amyloid Beta (Aβ) 1-42 Plasma Concentration at Week 12(Baseline (LFAN Randomization ), 6 hours pose-dose at Week 12 (LFBF))
- Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog11) at Week 12(Baseline (LFAN Randomization), 12 weeks (LFBF))
- Change From Baseline in Resource Utilization in Dementia-Lite Questionnaire (RUD-Lite) at Week 12(Baseline (LFAN Randomization), 12 weeks (LFBF))
- Change From Baseline in Mini-Mental State Examination (MMSE) at Week 24(Baseline (LFAN Randomization), 24 weeks (LFBF))
- Change From Baseline in EuroQol-5D (EQ-5D) at Week 24(Baseline (LFAN Randomization), 24 weeks (LFBF))
- Change From Baseline in Amyloid Imaging Positron Emission Tomography (AV-45-PET) at Week 12(Baseline (LFAN Randomization), 12 weeks (LFBF))
- Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog12) at Week 12(Baseline (LFAN Randomization), 12 weeks (LFBF))
- Mean Concentration of LY450139(3 months (pre-dose, 2, 4, and 6 hours after dosing )(LFBF))
- Change From Baseline in Clinical Dementia Rating Scale (Sum of Boxes) (CDR-SB) at Week 24(Baseline (LFAN Randomization), 24 weeks (LFBF))