The study provides evidence that confirms the efficacy of zonisamide 50 mg/d for reduction in "off" time in PD patients with wearing-off phenomena.

Background: We previously showed that zonisamide significantly improved parkinsonian symptoms by a multicenter, double-blind clinical trial. Aim: To confirm the efficacy of zonisamide on Parkinson's disease, a phase 3, randomized, placebo-controlled, multicenter, double-blind trial was carried out in Japan. Methods: Participants had advanced Parkinson's disease taking L-dopa with at least one other antiparkinson drug, but were developing a deterioration of response to L-dopa therapy. The trial consisted of a 2-week initial phase (singleblind, with administration of placebo) and a 12-week treatment phase (doubleblind, with patients randomly assigned to either placebo, or zonisamide 25 or 50 mg/day). Patients were evaluated using the Unified Parkinson's Disease Rating Scale (UPDRS). Results: A total of 185 patients (mean age 64.8 years; mean duration 7.5 years) were included in the efficacy analysis (placebo, zonisamide 25 mg, 50 mg; 63, 61, 61 patients, respectively). When compared with the placebo group, the UPDRS Part III total score at final assessment (the primary end-point for efficacy) significantly improved (P = 0.029) in the zonisamide 25 mg group. After 12 weeks of therapy, the UPDRS Part III total score significantly improved in both the zonisamide 25 mg (P = 0.038) and 50 mg groups (P = 0.049), compared with the placebo group. Neither the zonisamide 25 mg nor 50 mg group differed significantly from the placebo group in the incidence of adverse events (P = 0.363 and P = 0.713, respectively). Conclusion: These findings confirmed that zonisamide is well tolerated and efficacious in the treatment of advanced Parkinson's disease.

The present study evaluated large-scale claims-based datasets and found that high-dose prescriptions and antipsychotic polypharmacy among Japanese outpatients were not as prevalent as has been previously thought. Copyright © 2017 John Wiley & Sons, Ltd.

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.

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The secondary ionization of lithium metal and lithium iodide by contact with an argon ECR plasma was studied. Lithium and argon ion densities in the lithium-argon mixture plasma were diagnosed by using double probes, a photospectrometer and a mass spectrometer. According to plasma diagnostics, the apparent ionization cross sections were ∼ 10 −16 m 2 for lithium metal and ∼ 10 −17 m 2 for lithium iodide. This ionization method produces a low-temperature plasma which would be appropriate for ion cyclotron resonance isotope separation.

Patients with dementia with Lewy bodies (DLB) experience worsening axial symptoms with disease progression, which can negatively affect quality of life. Previous phase 2 and 3 clinical trials conducted in Japan showed that zonisamide improved parkinsonism in patients with DLB. In the present study, we performed a post hoc analysis of pooled data from the previous phase 2 and 3 trials to examine the effect of zonisamide on axial symptoms in this patient group. In our pooled analysis, the primary outcome was the change from baseline to 12 weeks in axial symptom score, measured as the sum of Unified Parkinson's Disease Rating Scale Part III items relevant to gait/balance/midline function. A total of 498 patients were included in this analysis. Zonisamide 25 mg and 50 mg significantly reduced the axial symptom score at week 12 compared with placebo ( p < 0.01 and p < 0.001, respectively, by mixed model of repeated measures). Our findings indicate that zonisamide may improve axial symptoms in DLB with parkinsonism and, thus, may potentially reduce the risk of falls and improve quality of life in this vulnerable patient population.

Objectives: We performed a post-hoc analysis of clinical trial data with the goal of investigating whether diabetic subgroups identified by data-driven clustering respond differently to imeglimin. Methods: Data from randomized, double-blind clinical trials of imeglimin as monotherapy or add-on to insulin therapy were included in the analysis. For monotherapy, 1) duration of type 2 diabetes, 2) baseline BMI, 3) baseline HbA1c, and 4) baseline HOMA-β, and for add-on to insulin therapy, the first three and 4) insulin total daily dose were applied as coordinates to form clusters by the non-hierarchical k-means method. The efficacy of imeglimin were examined for each cluster. Results: We identified four clusters of patients with diabetes, which had significantly different patient characteristics. Cluster 1 was a group with lower values of all four indices compared to the total patient population before cluster segregation, cluster 2 was a group with longer duration of diabetes, cluster 3 was a group with higher baseline BMI and higher HOMA-β (for monotherapy) or higher insulin total daily dose (for add-on to insulin therapy), and cluster 4 was a group with higher baseline HbA1c. The improvement in HbA1c with imeglimin differed significantly among the four clusters. The mean change differences versus placebo for imeglimin in monotherapy ranged from -0.64% to -1.27%, and add-on to insulin therapy ranged from -0.31% to -0.82%. In all clusters except for cluster 3 in the add-on to insulin therapy, imeglimin showed statistically significant HbA1c improvement compared to placebo. Conclusion: Data-driven clustering of patients with type 2 diabetes allowed us to identify subgroups that respond differently to imeglimin in improving HbA1c. This new stratification might help to tailor and target the imeglimin treatment to patients who would benefit most. Disclosure K.Hagi: Employee; Sumitomo Pharma. K.Kochi: Employee; Sumitomo Dainippon Pharma Co., Ltd., Sumitomo Pharma Co., Ltd. H.Watada: Research Support; Boehringer Ingelheim Japan, Inc., Mitsubishi Tanabe Pharma Corporation, LifeScan Diabetes Institute, Eli Lilly Japan K.K., Sun Pharmaceutical Industries Ltd., Teijin Pharma Limited, Taisho Pharmaceutical Holdings Co., Ltd., Ono Pharmaceutical Co., Ltd., Kowa Company, Ltd., Merck Sharp & Dohme Corp., Sanwa Kagaku Kenkyusho, Speaker's Bureau; Mitsubishi Tanabe Pharma Corporation, Taiho Pharmaceutical Co. Ltd., Novo Nordisk, Abbott Japan Co., Ltd., Astellas Pharma Inc., Merck Sharp & Dohme Corp., Kissei Pharmaceutical Co., Ltd., AstraZeneca, Ono Pharmaceutical Co., Ltd., Boehringer Ingelheim Japan, Inc., Sanofi, Sun Pharmaceutical Industries Ltd., Eli Lilly Japan K.K. K.Kaku: Advisory Panel; Novo Nordisk, Consultant; Sanwa Kagaku Kenkyusho, Speaker's Bureau; Astellas Pharma Inc., Daiichi Sankyo, Eli Lilly Japan K.K., Boehringer Ingelheim Japan, Inc., Kowa Company, Ltd., Mitsubishi Tanabe Pharma Corporation, Taiho Pharmaceutical Co. Ltd., Takeda Pharmaceutical Co., Ltd. K.Ueki: Advisory Panel; Abbott Japan Co., Ltd., Research Support; Abbott Japan Co., Ltd., Boehringer Ingelheim Japan, Inc., Eli Lilly Japan K.K., Sumitomo Dainippon Pharma Co., Ltd., Novo Nordisk, Sanofi K.K., MSD Life Science Foundation, Takeda Pharmaceutical Co., Ltd., Speaker's Bureau; Boehringer Ingelheim Japan, Inc., Eli Lilly Japan K.K., Astellas Pharma Inc., AstraZeneca, Sumitomo Dainippon Pharma Co., Ltd., Novo Nordisk, Taiho Pharmaceutical Co. Ltd., Kowa Company, Ltd., Mitsubishi Tanabe Pharma Corporation, Ono Pharmaceutical Co., Ltd.