Effect of patient characteristics on the efficacy and safety of imeglimin monotherapy in Japanese patients with type 2 diabetes mellitus: A post-hoc analysis of two randomized, placebo-controlled trials.

AIMS/INTRODUCTION: Substantial variability in demographic and clinical characteristics exists among patients with type 2 diabetes mellitus, which may impact treatment. This post-hoc analysis evaluated the efficacy and safety of imeglimin 1,000 mg twice daily (BID) monotherapy in type 2 diabetes mellitus patients according to demographic and clinical characteristics. MATERIALS AND METHODS: Data were pooled from two placebo-controlled, 24 week, randomized, double-blind studies in adults with type 2 diabetes mellitus. Outcomes (least squares mean [LSM] change in HbA1c from baseline to week 24, and safety) were analyzed according to subgroups based on demographics, clinical characteristics, and comorbidities. RESULTS: The difference in LSM change in HbA1c from baseline to week 24 was statistically significant for imeglimin vs placebo in all patient subgroups analyzed (P < 0.05 each), including demographics (age, body mass index), clinical characteristics (duration of type 2 diabetes mellitus, chronic kidney disease [CKD] stage, and prior medication use) and comorbidities (hypertension, dyslipidemia, risk of hepatic fibrosis and liver function parameter status). A statistically significant separation from placebo in HbA1c was observed at week 4 and maintained through week 24. No new safety concerns were identified with imeglimin in any patient subpopulations. CONCLUSIONS: The efficacy and safety of imeglimin was demonstrated across patient subgroups, irrespective of baseline demographic and clinical characteristics. Our findings confirm the efficacy and safety of imeglimin across a broad spectrum of patients with type 2 diabetes mellitus.

Trends in Prescribing Antipsychotics for Children and Adolescents in Japan: A Descriptive Epidemiological Study Using a Large-Scale Pharmacy Dataset.

Little is known about antipsychotic prescription patterns among children and adolescents in Japan, particularly in outpatient settings. We investigated the prevalence and trends of antipsychotic prescription for outpatients aged ≤ 17 years receiving a first antipsychotic prescription from 2006 to 2012 based on a large-scale dispensation dataset. Measurements included age, sex, department of diagnosis and treatment, type of prescription (monotherapy or polytherapy), antipsychotic dosage, and concomitant psychotropic drugs. Of the 10,511 patients, 65.1% were aged 13-17 years, and 52.9% were males. Second-generation antipsychotic monotherapy prescriptions increased from 53.8% in 2006 to 78.3% in 2012. Risperidone was the most frequently prescribed antipsychotic, followed by aripiprazole and olanzapine. Approximately 25.0% of patients were prescribed an initial dose less than recommended. Second-generation antipsychotic monotherapy is currently the most frequent prescription pattern among outpatients aged ≤ 17 years receiving an initial antipsychotic prescription.

Zonisamide improves axial symptoms in dementia with Lewy bodies with parkinsonism: Post hoc analysis of clinical trials.

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.

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: 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.

Trends in antipsychotic prescriptions for Japanese outpatients during 2006-2012: a descriptive epidemiological study.

PURPOSE: This study aimed to assess the trends in antipsychotic prescriptions for outpatients in Japan, where a community-based approach to mental healthcare is emphasized. METHODS: This descriptive epidemiological study used claims data from 1038 community pharmacies across Japan. Outpatients who were ≥18 years old and receiving their initial antipsychotic prescription during 2006-2012 were evaluated. The annual trends were reported for monotherapies, polypharmacy, antipsychotic doses, and the concurrent prescription of psychotropic medications. RESULTS: The 152 592 outpatients included 101 133 (66%) adults (18-64 years old) and 51 459 (34%) older adults (≥65 years old). Among the adults, second-generation antipsychotic monotherapy prescriptions increased from 49% in 2006 to 71% in 2012, first-generation antipsychotic monotherapy prescriptions decreased from 29 to 14%, and antipsychotic polypharmacy decreased from 23 to 15%, respectively. Among the older adults, second-generation antipsychotic monotherapy prescriptions increased from 64 to 82%, first-generation antipsychotic monotherapy prescriptions decreased from 29 to 12%, and antipsychotic polypharmacy decreased from 7 to 6%, respectively. During the study period, >80% of the adults and >90% of the older adults received antipsychotics at risperidone-equivalent doses of <6 mg/day. Anxiolytics/hypnotics, antidepressants, antiparkinson agents, mood stabilizers, and anti-dementia agents were concurrently prescribed with antipsychotics for 70, 33, 20, 20, and 0.3% of the adults and for 43, 16, 19, 8, and 16% of the older adults, respectively. CONCLUSIONS: 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.

Zonisamide improves wearing-off in Parkinson's disease: A randomized, double-blind study.

BACKGROUND: Previously, we reported 50 mg/d zonisamide improved wearing-off without increasing dyskinesia in patients with Parkinson's disease (PD). METHODS: To determine the efficacy of zonisamide for treatment of "off" time in PD patients, we conducted a multicenter, randomized, double-blind, parallel-group, placebo-controlled study in Japan. Patients with PD and wearing-off received placebo for 4 weeks and then were treated for 12 weeks with zonisamide 25 or 50 mg/d or placebo, in addition to their previous therapy. The primary endpoint was the change from baseline in daily "off" time as determined by patients' diaries at the final assessment. Secondary endpoints included changes from baseline in the total scores of the Unified Parkinson's Disease Rating Scale Parts I, II, III, and IV, the dyskinesia duration, and PDQ-39 score. RESULTS: Of 422 patients enrolled, 389 (131 for placebo, 130 for zonisamide 25 mg, and 128 for zonisamide 50 mg) were randomized, and 354 (120, 119, and 115, respectively) completed the study. The "off" time significantly reduced by 0.719 ± 0.179 h for zonisamide, 50 mg compared with placebo (0.011 ± 0.173 h, P = 0.005). Although the incidence of somnolence was higher for zonisamide (3.1% for zonisamide 25 mg, 6.3% for zonisamide 50 mg) than for placebo (2.3%), the incidences of the other adverse events, including dyskinesia or hallucination, for both zonisamide treatments were comparable to those for placebo. CONCLUSION: 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.