1. Adjunct zonisamide to levodopa for DLB parkinsonism: A randomized double-blind phase 2 study
- Author
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Kenji Kosaka, Toshinari Odawara, Masatoshi Nakamura, Kazuko Hasegawa, Sayaka Iiyama, Miho Murata, and Masaaki Tagawa
- Subjects
0301 basic medicine ,Lewy Body Disease ,Male ,medicine.medical_specialty ,Zonisamide ,Placebo ,Severity of Illness Index ,law.invention ,Antiparkinson Agents ,Levodopa ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,Double-Blind Method ,law ,Internal medicine ,Severity of illness ,medicine ,Clinical endpoint ,Dementia ,Humans ,Adverse effect ,Aged ,Aged, 80 and over ,business.industry ,Parkinsonism ,Middle Aged ,medicine.disease ,030104 developmental biology ,Treatment Outcome ,Drug Therapy, Combination ,Female ,Neurology (clinical) ,business ,030217 neurology & neurosurgery ,medicine.drug - Abstract
ObjectiveTo investigate the efficacy and safety of zonisamide as an adjunct to levodopa therapy for parkinsonism in patients with dementia with Lewy bodies (DLB).MethodsThis phase 2, placebo-controlled, randomized, double-blind study consisted of run-in (placebo, 4 weeks) and treatment (placebo or zonisamide 25 or 50 mg once daily, 12 weeks) periods. Outpatients diagnosed with probable DLB were eligible for inclusion. The primary endpoint was the change from baseline in Unified Parkinson's Disease Rating Scale (UPDRS) part 3 total score at week 12. Cognitive function, behavioral and psychological symptoms of dementia (BPSD), caregiver burden, other UPDRS parts as secondary endpoints, and safety were also assessed.ResultsOverall, 158 patients with DLB received the study drug; 21 discontinued during treatment and 137 completed treatment. Improvement in UPDRS part 3 total score at week 12 was significantly greater in the zonisamide 50 mg group compared with placebo (between-group difference −4.1; 95% confidence interval −6.8 to −1.4; p = 0.003). Zonisamide did not worsen cognitive function, BPSD, or caregiver burden. The overall incidence of adverse events was higher in the zonisamide 50 mg than the 25 mg and placebo groups (65.3%, 43.1%, and 50.0%, respectively); similar rates of serious adverse events were observed among all groups.ConclusionZonisamide (adjunctive to levodopa) improved parkinsonism accompanying DLB without worsening cognitive function or psychiatric symptoms.Clinical trial registrationJapicCTI-122040.Classification of evidenceThis study provides Class I evidence that zonisamide (adjunctive to levodopa) improves parkinsonism and is well-tolerated in patients with DLB.
- Published
- 2017