Sixteen-Week Interventional Study to Evaluate the Clinical Effects and Safety of Rivastigmine Capsules in Chinese Patients with Alzheimer’s Disease

Article type: Research Article

Authors: Jia, Jianping^{a; *} | Ji, Yong^{b; c} | Feng, Tao^{c; d} | Ye, Qinyong^e | Peng, Dantao^f | Kuang, Weihong^g | Ning, Yuping^h | Liang, Zhihouⁱ | Fan, Dongsheng^j | Wei, Wenshi^k | Li, Yansheng^l | Xiao, Shifu^m

Affiliations: [a] Innovation Center for Neurological Disorders and Department of Neurology, Xuanwu Hospital, Capital University of Medical Sciences, Beijing, China | [b] Department of Cognitive Disorder, Beijing Tiantan Hospital, Capital Medical University, Beijing, China | [c] China National Clinical Research Center for Neurological Disease, Beijing, China | [d] Movement Disorders Center, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China | [e] Department of Neurology, The Affiliated Union Hospital of Fujian Medical University, Fuzhou, China | [f] Department of Neurology, China-Japan Friendship Hospital, Beijing, China | [g] Mental Health Center, West China Hospital of Sichuan University, Chengdu, China | [h] Department of Psychiatry, Affiliated Brain Hospital of Guangzhou Medical University (Guangzhou Huiai Hospital), Guangzhou, China | [i] Department of Neurology, Affiliated Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China | [j] Department of Neurology, Peking University Third Hospital, Beijing, China | [k] Department of Geriatrics, Huadong Hospital, Fudan University, Shanghai, China | [l] Department of Neurology, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China | [m] Department of Geriatric Psychiatry, Alzheimer’s Disease and Related Disorders’ Center, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, China

Correspondence: [*] Correspondence to: Jianping Jia, Department of Neurology, Innovation Center for Neurological Disorders, Xuan Wu Hospital, Capital Medical University, Beijing 100053, P.R. China. Tel.: +86 10 83198730; Fax: +86 1083171070; E-mail: [email protected].

Abstract: Background:Rivastigmine is a cholinesterase inhibitor, approved for the treatment of mild-to-moderate dementia of Alzheimer’s type. Objective:To explore the efficacy and safety of the maximal tolerated dose of rivastigmine capsules in Chinese patients with mild-to-moderate Alzheimer’s disease (AD). Methods:The study was a multicenter, open-label, single-arm, phase IV clinical study in mild-to-moderate drug-naïve AD patients treated with rivastigmine capsules. The primary endpoint was the changes in the total scores of Alzheimer’s Disease Assessment Scale-Cognitive subscale (ADAS-Cog) from baseline to week 16. Secondary endpoints included changes in the scores of the following assessment scales and safety: Alzheimer’s Disease Cooperative Study; Activities of Daily Living; Mini-Mental Status Examination (MMSE); Neuropsychiatry Index (NPI), and Caregiver Burden Inventory. Results:222 patients were enrolled. Of these, 136 (75.1%) patients received and maintained the effective dose (≥6 mg/d) of rivastigmine for at least 4 weeks. The ADAS-Cog scale score improved in rivastigmine-treated patients at week 16 compared with baseline (p < 0.001) by 2.0 (95% CI: –3.0 to –1.1) points, which met the pre-defined superiority criteria. NPI-10 and NPI-12 scores improved by 3.6 and 4.0 points at week 16 (p = 0.001, p < 0.001), respectively. A total of 107 patients (59.1%) experienced adverse effects (AEs) during the study; common AEs included nausea (20.5%), vomiting (16.6%), anorexia (7.8%), dizziness (7.7%), and diarrhea (7.2%). Conclusion:This was the first phase IV study on rivastigmine in mainland China. The study preliminarily demonstrated that rivastigmine capsules showed good tolerability and efficacy in mild-to-moderate AD patients with the maximal tolerated dose.

Keywords: Alzheimer’s disease, capsule, Chinese population, rivastigmine

DOI: 10.3233/JAD-190791

Journal: Journal of Alzheimer's Disease, vol. 72, no. 4, pp. 1313-1322, 2019