Dataset Information

Efficacy and Safety of Zonisamide in Dementia with Lewy Bodies Patients with Parkinsonism: A Post Hoc Analysis of Two Randomized, Double-Blind, Placebo-Controlled Trials.

ABSTRACT:

Background

Although previous phase II and III clinical trials conducted in Japan showed that zonisamide improved parkinsonism in patients with dementia with Lewy bodies (DLB), some differences in efficacy outcomes were observed between the trials.

Objective

We aimed to further examine the efficacy and safety of zonisamide in DLB patients with parkinsonism in a post hoc analysis of pooled data from the previous phase II and III trials.

Methods

Both trials featured a 4-week run-in period followed by a 12-week treatment period with a double-blind, placebo-controlled, parallel-group, randomized, multicenter trial design. In our pooled analysis, the primary outcome was the change in Unified Parkinson's Disease Rating Scale (UPDRS) part III total score. Other outcomes included the changes in Mini-Mental State Examination (MMSE) and Neuropsychiatric Inventory-10 (NPI-10) scores, and the incidence of adverse events.

Results

Zonisamide significantly decreased the UPDRS part III total and individual motor symptom scores but did not affect the MMSE or NPI-10 scores at week 12. There was no difference in the incidence of adverse events between the zonisamide and placebo groups except for decreased appetite, which had an increased frequency in the zonisamide 50?mg group compared with placebo.

Conclusion

Our findings indicate that zonisamide improved parkinsonism with DLB without deterioration of cognitive function and or worsening behavioral and psychological symptoms of dementia.

SUBMITTER: Hasegawa K

PROVIDER: S-EPMC7902955 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Efficacy and Safety of Zonisamide in Dementia with Lewy Bodies Patients with Parkinsonism: A Post Hoc Analysis of Two Randomized, Double-Blind, Placebo-Controlled Trials.

Hasegawa Kazuko K Kochi Kenji K Maruyama Hidenori H Konishi Osamu O Toya Shunji S Odawara Toshinari T

Journal of Alzheimer's disease : JAD 20210101 2

<h4>Background</h4>Although previous phase II and III clinical trials conducted in Japan showed that zonisamide improved parkinsonism in patients with dementia with Lewy bodies (DLB), some differences in efficacy outcomes were observed between the trials.<h4>Objective</h4>We aimed to further examine the efficacy and safety of zonisamide in DLB patients with parkinsonism in a post hoc analysis of pooled data from the previous phase II and III trials.<h4>Methods</h4>Both trials featured a 4-week r ...[more]

PMID: 33337365

Similar Datasets

Project description:IntroductionThe efficacy of a cholinesterase inhibitor, donepezil, in patients with dementia with Lewy bodies (DLB) was investigated to confirm the superiority over placebo in the 12-week, double-blind phase of this phase III study.MethodsPatients with probable DLB (n = 142) were randomly assigned to placebo or to 5 mg or 10 mg of donepezil administered once daily for 12 weeks. The co-primary endpoints were changes in cognitive function assessed using the Mini-Mental State Examination (MMSE) and behavioral and neuropsychiatric symptoms using the Neuropsychiatric Inventory (NPI-2: hallucinations and fluctuations). The superiority of each active group over placebo was determined with simultaneous statistical significance in both endpoints. Safety evaluations included adverse events (AEs) and the unified Parkinson's disease rating scale (UPDRS) part III.ResultsThe predefined superiority of donepezil to the placebo was not confirmed in either active group in the primary analysis. MMSE score significantly improved compared to placebo in the 10 mg group (10 mg: 2.2 ± 0.4, placebo: 0.6 ± 0.5 (mean ± standard error); P = 0.016). The change in MMSE score in the 5 mg group was not significant (1.4 ± 0.5 (mean ± standard error); P = 0.232). Although NPI-2 improved compared to baseline in the active groups, the differences from placebo were not significant. Most AEs were mild or moderate. Although the incidence of parkinsonism was slightly higher in the 10 mg group, the change in the UPDRS score was minimal and without a significant difference from the placebo group.ConclusionsThe co-primary endpoints were not achieved in this trial. However, significant improvement in MMSE score was demonstrated with 10 mg, but not 5 mg, of donepezil. The evaluation of psychiatric symptoms might be affected by advanced education and instructions given to caregivers. Overall, donepezil was well tolerated in patients with DLB. With careful attention on gastrointestinal or parkinsonian symptoms, patients with DLB can safely benefit from treatment with donepezil.Trial registrationClinicalTrials.gov Identifier: NCT01278407 (trial registration date: 14 January 2011).

Project description:INTRODUCTION:Duloxetine has demonstrated efficacy in chronic low back pain (CLBP). We examined the predictors of response to duloxetine for CLBP. PATIENTS AND METHODS:This was a post hoc analysis of pooled data from 4 double-blind, ran-domized, placebo-controlled trials of duloxetine (60 mg/day for 12-14 weeks) in adult patients with CLBP. Primary outcome was proportion of patients with ?30% reduction in Brief Pain Inventory (BPI) average pain ("pain reduction") at 12-14 weeks. The proportion of patients with ?30% and ?50% (secondary outcome) pain reduction in duloxetine and placebo groups was compared. Variables for responder analyses were early improvement (?15% pain reduction at Week 2), sex, age, baseline BPI average pain score, duration of CLBP, and number of painful body sites according to the Michigan Body Map (?2 vs 1 [isolated CLBP]; 1 trial); relative risk (RR) and 95% confidence interval (CI) were calculated. RESULTS:Compared with placebo (n = 653), a greater proportion of duloxetine-treated patients (n = 642) achieved ?30% (59.7% vs 47.8%; P < 0.001) and ?50% pain reduction (48.6% vs 35.1%; P < 0.001). Among duloxetine-treated patients, early improvement was associated with greater likelihood of ?30% (RR [95% CI], 2.91 [2.30-3.67]) or ?50% (3.24 [2.44-4.31]) pain reduction. Women were slightly more likely than men to achieve ?30% (RR [95% CI], 1.14 [1.00-1.30]) or ?50% (1.17 [0.99-1.38]) pain reduction. Response rates were similar between age, CLBP duration, and baseline BPI average pain score subgroups. Patients with ?2 painful sites were more likely to respond to duloxetine 60 mg relative to placebo than patients with isolated CLBP (RR, duloxetine vs placebo [95% CI]: ?30% reduction, ?2 painful sites 1.40 [1.18-1.66], isolated CLBP 1.07 [0.78-1.48]; ?50% reduction, ?2 painful sites 1.51 [1.20-1.89], isolated CLBP 1.23 [0.81-1.88]). CONCLUSION:Early pain reduction was indicative of overall response. Patients with multiple painful sites had more benefit from duloxetine than patients with isolated CLBP.

Project description:IntroductionDementia with Lewy bodies (DLB) is the third most common type of dementia after Alzheimer's disease (AD) and vascular dementia. Treatment is targeted at specific disease manifestations/symptoms. While donepezil is approved for the treatment of DLB in Japan, to date no other treatment has been approved for this indication anywhere in the world. Notwithstanding, many of the medications that are approved for AD are widely used in the treatment of DLB with varying degrees of success. Consequently, clinical evidence is limited, and there is a need to understand the comparative efficacy and safety of currently used therapies for DLB. The aim of this study was to conduct a network meta-analysis (NMA) to evaluate the outcomes of the available treatment options based on currently used trial endpoints.MethodsUsing data from a previously published systematic review, we conducted an NMA to investigate the efficacy and safety of treatments in patients with DLB. Networks were based on change from baseline of efficacy endpoints (Mini-Mental State Examination; Neuropsychiatric Inventory; Unified Parkinson's Disease Rating Scale) and rate of safety events (overall adverse events [AEs]; discontinuations; discontinuations due to AEs; psychiatric events).ResultsFocused around a common treatment option of placebo, the NMA comprised studies on donepezil, rivastigmine, memantine and quetiapine. Donepezil 3 mg, 5 mg and 10 mg doses were compared against each other and placebo. Overall, donepezil consistently performed better than the alternative treatments when compared to placebo for all efficacy and safety endpoints. However, the small sample size and/or heterogeneity of the studies led to uncertainty, resulting in no statistically significant differences favouring any treatment above another or placebo.ConclusionDespite the lack of statistical significance, when assessing the efficacy and safety outcomes for each drug in the evidence network, donepezil appeared to have a more favourable overall benefit/risk profile for patients with DLB. Further comparative trials are required to improve understanding of the true difference between existing and potential future treatment options.

Dataset Information

Efficacy and Safety of Zonisamide in Dementia with Lewy Bodies Patients with Parkinsonism: A Post Hoc Analysis of Two Randomized, Double-Blind, Placebo-Controlled Trials.

Background

Objective

Methods

Results

Conclusion

Publications

Efficacy and Safety of Zonisamide in Dementia with Lewy Bodies Patients with Parkinsonism: A Post Hoc Analysis of Two Randomized, Double-Blind, Placebo-Controlled Trials.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets