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Rivastigmine in moderately severe-to-severe Alzheimer's disease: Severe Impairment Battery factor analysis.

ABSTRACT: The Severe Impairment Battery (SIB) is validated for assessing cognition in patients with severe dementia. The current analysis aimed to further investigate the cognitive efficacy of rivastigmine capsules, as assessed by SIB factor scores, in patients with moderately severe-to-severe Alzheimer's disease (AD).This was a retrospective analysis of a 26-week, multicenter, randomized, double-blind, placebo-controlled study of oral rivastigmine conducted in Spain. Previously reported outcome measures included the full SIB. Current analyses examined calculated scores and effect sizes for the change from baseline at Week 26 on: newly defined SIB subscales (derived by a factor analysis of the 40 SIB items, using the PROC FACTOR function (SAS)); previously defined memory, language and praxis subscales (derived by previous analysis of the nine SIB domains); and the individual SIB items. Treatment differences were assessed.SIB data were provided by 104 rivastigmine-treated patients and 106 patients receiving placebo (Intent-To-Treat Last Observation Carried Forward population). Significantly less decline was observed on the previously defined memory and language subscales, and the newly defined working memory/memory subscale in rivastigmine-treated patients (all P?

SUBMITTER: Ferris S

PROVIDER: S-EPMC3978681 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Rivastigmine in moderately severe-to-severe Alzheimer's disease: Severe Impairment Battery factor analysis.

Ferris Steven S Karantzoulis Stella S Somogyi Monique M Meng Xiangyi X

Alzheimer's research & therapy 20131218 6

<h4>Introduction</h4>The Severe Impairment Battery (SIB) is validated for assessing cognition in patients with severe dementia. The current analysis aimed to further investigate the cognitive efficacy of rivastigmine capsules, as assessed by SIB factor scores, in patients with moderately severe-to-severe Alzheimer's disease (AD).<h4>Methods</h4>This was a retrospective analysis of a 26-week, multicenter, randomized, double-blind, placebo-controlled study of oral rivastigmine conducted in Spain. ...[more]

PMID: 24351447

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Project description:IntroductionThe US Food and Drug Administration approved a 23 mg daily dose of donepezil for treatment of moderate to severe Alzheimer's disease (AD) based on outcomes from a large trial comparing the 23 mg/day dose with the standard 10 mg/day dose. Results from this study indicated that after 24 weeks, donepezil 23 mg/day provided significant cognitive benefits over donepezil 10 mg/day, measured using the Severe Impairment Battery (SIB). In the analyses reported herein, we further characterize the range of cognitive domains impacted by treatment with donepezil 23 mg/day.MethodsA post hoc analysis was conducted using data from a 24-week, randomized, double-blind trial comparing donepezil 23 mg/day versus 10 mg/day in 1,467 patients with moderate to severe AD (baseline Mini-Mental State Examination (MMSE) score 0 to 20). Changes from baseline to week 24 in the nine SIB domain scores were analyzed in the intent-to-treat (ITT) population (baseline MMSE 0 to 20), in patients with more severe baseline AD (MMSE 0 to 16), and in severity strata based on baseline MMSE scores (0 to 5, 6 to 10, 11 to 15, 16 to 20).ResultsIn the ITT population, changes in six of the nine SIB domains favored donepezil 23 mg/day over donepezil 10 mg/day. LS mean treatment differences were significant for the language, visuospatial ability, and construction domains. In the more advanced cohort of patients (MMSE 0 to 16 at baseline), LS mean treatment differences were statistically significant favoring donepezil 23 mg/day in five of the nine domains: language, memory, visuospatial ability, attention, and construction. Descriptive analysis of LS mean changes in SIB domain scores in the four baseline severity strata showed variable patterns of response; overall, cognitive benefits of donepezil 23 mg/day were greatest in patients with MMSE scores of 0 to 15.ConclusionsThese results suggest that donepezil 23 mg/day provides benefits over 10 mg/day across a range of cognitive domains. The magnitude of benefit and domains impacted varied depending on the stage of AD; significant benefits with higher dose donepezil were most apparent at more advanced stages of AD and were most prominent in the language domain.

Project description:AimThe Severe Impairment Battery (SIB), a reliable cognitive measure for evaluating treatment response in advanced Alzheimer's disease (AD), takes approximately 20 min to administer. A recently derived 8-item version of the SIB - the SIB-8 - which takes about 3 min to administer, may represent a more convenient tool for use in clinical practice. The current analyses further explored the SIB-8 scale with respect to its validity and sensitivity.MethodsA post hoc analysis was performed using data from a 24-week trial of donepezil 23 mg/day and 10 mg/day in > 1400 patients with moderate to severe AD [baseline Mini-Mental State Examination (MMSE) score 0-20]. Treatment effects on cognition (patterns of score change) were assessed using the full SIB and SIB-8 in the total study population and subgroups based on concomitant memantine use and baseline MMSE. Internal consistency/agreement and correlations between the SIB and SIB-8 and other clinical end points were evaluated.ResultsAssessment of score changes from baseline to week 24 with donepezil (23 or 10 mg/day) demonstrated comparable patterns of change when using the SIB-8 and the full SIB, despite inherent differences in the total score ranges for the two scales. Internal consistency/agreement between the full SIB and SIB-8 was good (Cronbach's alphas: 0.77-0.95). SIB-8 scores reliably correlated with SIB total scores (r = 0.859, baseline; r = 0.900, week 24; p < 0.0001), as well as MMSE scores (r = 0.7163, baseline; r = 0.7963, week 24; p < 0.0001). Scores on both SIB scales were moderately associated with functional measures at baseline and week 24.ConclusionsIn this post hoc analysis, similar treatment effects were measured by the full SIB and the SIB-8. Very good internal consistency/agreement and strong correlations between the SIB and the more rapid and convenient SIB-8 indicate that the SIB-8 may be a useful and efficient clinical proxy for the full SIB in evaluating treatment response in patients with advanced AD.

Project description:IntroductionThe glomerular filtration rate (GFR), a measure of renal function, decreases by approximately 10 mL/min every 10 years after the age of 40 years, which could lead to the accumulation of drugs and/or renal toxicity. Pharmacokinetic studies of drugs excreted both renally and non-renally are desirable in patients with impaired renal function, defined by parameters including estimated GFR (eGFR) and creatinine clearance (CLCR).ObjectiveWe describe here a population pharmacokinetic analysis of the possible effects of renal impairment on steady-state plasma concentrations of rivastigmine and its metabolite NAP226-90 after rivastigmine patch (5 cm2 [4.6 mg/24 h], 10 cm2 [9.5 mg/24 h], 15 cm2 [13.3 mg/24 h], and 20 cm2 [17.4 mg/24 h]) and capsule (1.5, 3, 4.5, and 6 mg/12 h) treatment in patients with Alzheimer's disease.MethodsThe data used to conduct the current pharmacokinetic analysis were obtained from the pivotal phase III, 24-week, multicenter, randomized, double-blind, placebo- and active-controlled, parallel-group study (IDEAL). One blood sample was collected from each patient at steady-state to measure plasma concentrations of rivastigmine and NAP226-90 using a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. The steady-state plasma concentrations of rivastigmine and NAP226-90 were plotted against CLCR and eGFR data, and boxplots were constructed after stratification by renal function.ResultsThe two groups (mild/no renal impairment vs. moderate/severe/end-stage renal impairment) showed comparable demographic covariates for all patch sizes and capsule doses. No correlation was observed between CLCR or eGFR and plasma concentrations of rivastigmine or NAP226-90. Boxplots of concentrations of rivastigmine or NAP226-90 for each dose largely overlapped for patch and capsule. Additionally, model-based estimates of plasma concentrations adjusted for body weight yielded similar results.ConclusionThe results of this study show that renal function does not affect rivastigmine or NAP226-90 steady-state plasma concentrations, and no dose adjustment in patients with renal impairment is required. CLINICALTRIALS.GOV: NCT00099242.

Dataset Information

Rivastigmine in moderately severe-to-severe Alzheimer's disease: Severe Impairment Battery factor analysis.

Publications

Rivastigmine in moderately severe-to-severe Alzheimer's disease: Severe Impairment Battery factor analysis.

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