Subgroup Analysis of US and Non-US Patients in a Global Study of High-Dose Donepezil (23 mg) in Moderate and Severe Alzheimer’s Disease

2012 ◽  
Vol 27 (6) ◽  
pp. 421-432 ◽  
Author(s):  
Stephen Salloway ◽  
Jacobo Mintzer ◽  
Jeffrey L. Cummings ◽  
David Geldmacher ◽  
Yijun Sun ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
High Dose ◽  
Efficacy And Safety ◽  
Global Function ◽  
The Us ◽  
The World ◽  
Cognitive Benefits ◽  
Post Hoc ◽  
Patient Subgroups

To better understand responses in the large number of US-based patients included in a global trial of donepezil 23 mg/d versus 10 mg/d for moderate-to-severe Alzheimer’s disease (AD), post hoc exploratory analyses were performed to assess the efficacy and safety in US and non-US (rest of the world [RoW]) patient subgroups. In both subgroups, donepezil 23 mg/d was associated with significantly greater cognitive benefits than donepezil 10 mg/d. Significant global function benefits of donepezil 23 mg/d over 10 mg/d were also observed in the US subgroup only. Compared with RoW patients, US patients had relatively more severe AD, had been treated with donepezil 10 mg/d for longer periods prior to the start of the study, and a higher proportion took concomitant memantine. In both subgroups, donepezil had acceptable tolerability; overall incidence of treatment-emergent adverse events was higher in patients receiving donepezil 23 mg/d compared with donepezil 10 mg/d.

scholarly journals Effects of Body Weight on the Safety of High-dose Donepezil in Alzheimer’s Disease: Post-hoc Analysis of a Multicenter, Randomized, Open-label, Parallel Design, Three-arm Clinical Trial

2020 ◽  
Author(s):  
Yun Jeong Hong ◽  
Hyun Jeong Han ◽  
YoungChul Youn ◽  
Kyung Won Park ◽  
Dong Won Yang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Body Weight ◽  
Dose Titration ◽  
High Dose ◽  
Open Label ◽  
Post Hoc Analysis ◽  
Cognitive Benefits ◽  
N 93 ◽  
Post Hoc

Abstract Background: Donepezil 23mg is considered for Alzheimer’s disease (AD) to optimize cognitive benefits; however, this increases adverse events (AEs), which can negatively influence drug adherence. We investigated whether baseline body weight (BW) differs based on the presence of AEs, and which factors were relevant to the safety of high-dose donepezil. Methods: This study was a post-hoc analysis of a multicenter randomized trial between 2014 and 2016. We included patients with moderate to severe AD treated with donepezil 10mg/day and the daily dose was escalated to 23mg with/without dose titration. Dose titration indicates 15mg/day of donepezil before the escalation or 10mg and 23mg/day on alternate days before the escalation during the first 4 weeks. The patients were divided into two groups according to the occurrence of AEs of special interest (AESIs) to compare baseline characteristics. We also assessed relationships between BW and AESIs.Results: Among 160 safety set population, baseline BWs were different between the AESI (+) (n=67) and AESI (-) (n=93) groups. Baseline BW was inversely correlated with the occurrence of AESIs (p=0.020), and this relationship was more prominent in the no-dose titration group (p=0.009) and disappeared in the dose titration groups (p>0.05).Conclusions: BW was the most important factor which correlated with cholinergic AEs. Hence, stepwise dose-titration should be considered, particularly in patients with low BW, to minimize the inverse relationship between BW and AEs occurrence. (‘Clinicaltrials.gov’ number NCT02550665 registered on Sep. 15, 2015)

scholarly journals Effects of Body Weight on the Safety of High-Dose Donepezil in Alzheimer’s Disease: Post hoc Analysis of a Multicenter, Randomized, Open-Label, Parallel Design, Three-Arm Clinical Trial

2021 ◽  
pp. 1-7
Author(s):  
Yun Jeong Hong ◽  
Hyun Jeong Han ◽  
Young Chul Youn ◽  
Kyung Won Park ◽  
Dong Won Yang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Body Weight ◽  
Dose Titration ◽  
High Dose ◽  
Open Label ◽  
Post Hoc Analysis ◽  
Safety Population ◽  
Cognitive Benefits ◽  
Post Hoc

<b><i>Background:</i></b> Donepezil 23 mg is considered for Alzheimer’s disease (AD) to optimize cognitive benefits; however, increased adverse events (AEs) can negatively influence drug adherence. We investigated whether body weight (BW) differs based on the presence of AEs, and which baseline factors were relevant to the safety of high-dose donepezil. <b><i>Methods:</i></b> This study was a post hoc analysis of a multicenter randomized trial between 2014 and 2016. We included patients with moderate to severe AD treated with 10 mg/day of donepezil, and the daily dose was escalated to 23 mg with/without dose titration. Dose titration indicates 15 mg/day of donepezil before escalation or 10 mg and 23 mg/day on alternate days before escalation during the first 4 weeks. The patients were divided into 2 groups based on occurrence of AEs of special interest (AESIs) to compare baseline characteristics. We also assessed relationships between BW and AESIs. <b><i>Results:</i></b> Among the 160 participants in the safety population, the baseline BWs differed between the AESI (+) (<i>n</i> = 67) and AESI (−) (<i>n</i> = 93) groups. Baseline BW was inversely correlated with the occurrence of AESIs (<i>p</i> = 0.020), and this relationship was prominent in the no-dose titration group (<i>p</i> = 0.009) but absent in the dose-titration groups (<i>p</i> &#x3e; 0.05). <b><i>Conclusions:</i></b> BW is the most important factor that correlated with cholinergic AEs. Hence, stepwise dose titration should be considered, particularly in patients with low BW, to minimize the inverse relationship between BW and the occurrence of AEs (“Clinicaltrials.gov” No. NCT02550665 registered on September 15, 2015).

scholarly journals Clinical Recommendations for the Use of Donepezil 23 mg in Moderate-to-Severe Alzheimer's Disease in the Asia-Pacific Region

2016 ◽  
Vol 6 (3) ◽  
pp. 382-395 ◽  
Author(s):  
Marwan Sabbagh ◽  
SeolHeui Han ◽  
SangYun Kim ◽  
Hae-Ri Na ◽  
Jae-Hong Lee ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Phase Iii ◽  
Asia Pacific ◽  
High Dose ◽  
Asian Patients ◽  
Severe Impairment ◽  
Valuable Treatment ◽  
Cognitive Benefits ◽  
Phase Iii Study

Background: The ‘Asia-Pacific Expert Panel (APEX) for donepezil 23 mg' met in November 2015 to review evidence for the recently approved high dose of donepezil and to provide recommendations to help physicians in Asia make informed clinical decisions about using donepezil 23 mg in patients with moderate-to-severe Alzheimer's disease (AD). Summary: In a global phase III study (study 326) in patients with moderate-to-severe AD, donepezil 23 mg/day demonstrated significantly greater cognitive benefits versus donepezil 10 mg/day, with a between-treatment difference in mean change in the Severe Impairment Battery score of 2.2 points (p < 0.001) in the overall population and 3.1 points (p < 0.001) in patients with advanced AD. A subanalysis of study 326 demonstrated that the benefits and risks associated with donepezil 23 mg/day versus donepezil 10 mg/day in Asian patients with moderate-to-severe AD were comparable to those in the global study population. Key Message: Donepezil 23 mg is a valuable treatment for patients with AD, particularly those with advanced disease. The APEX emphasized the importance of patient selection (AD severity, tolerability of lower doses of donepezil, and absence of contraindications), a stepwise titration strategy for dose escalation, and appropriate monitoring and counseling of patients and caregivers in the management of patients with AD.

scholarly journals Aducanumab for Alzheimer's Disease: An Update

2021 ◽  
Vol 4 (2) ◽  
Author(s):  
Thaarvena Retinasamy ◽  
Mohd. Farooq Shaikh
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Beta ◽  
Mode Of Action ◽  
The Us ◽  
The World ◽  
Accelerated Approval ◽  
Us Fda

The US FDA approved Aducanumab in June 2021 as the first Alzheimer's disease (AD) drug under its accelerated approval pathway. It has given some hope to patients suffering from AD around the world. Aducanumab is an antibody that targets one of the well-known key culprits of this disease, known as amyloid-beta (Aβ). The journey of Aducanumab was bumpy, and there are controversies around the rapid approval of this drug AD treatment. This article highlights the potential of Aducanumab in AD, its mode of action and controversies around it.

Clinical Efficacy and Safety of Donepezil on Cognitive and Global Function in Patients with Alzheimer’s Disease

2000 ◽  
Vol 11 (6) ◽  
pp. 299-313 ◽  
Author(s):  
Akira Homma ◽  
Masatoshi Takeda ◽  
Yukimichi Imai ◽  
Fukashi Udaka ◽  
Kazuo Hasegawa ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Efficacy ◽  
Efficacy And Safety ◽  
Global Function

The cost-utility of the rivastigmine transdermal patch in the management of patients with moderate Alzheimer's disease in the US

2009 ◽  
Vol 36 (S 02) ◽  
Author(s):  
A Brennan ◽  
B Nagy ◽  
A Brandtmüller ◽  
SK Thomas ◽  
M Gallagher ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cost Utility ◽  
Transdermal Patch ◽  
The Us ◽  
The Cost
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