title: Effectiveness and safety of generic memantine hydrochloride manufactured in China in the treatment of moderate to severe Alzheimer's disease: a multicenter, double-blind randomized controlled trial.
abstract: BACKGROUND
  Memantine hydrochloride is a N-methyl-D-aspartate (NMDA) antagonist that may be useful in the treatment of Alzheimer's disease.
  
  
  OBJECTIVE
  Compare the efficacy and safety of generic memantine hydrochloride produced in China to that of the imported proprietary version of the medication (Ebixa) in the treatment of moderate to severe Alzheimer's disease (AD).
  
  
  METHODS
  In this multicenter, double-blind randomized controlled trial 229 patients with moderate to severe AD were randomly assigned to a 16-week trial of either the generic preparation or the proprietary preparation of memantine hydrochloride. All participants were assessed at baseline and at 4, 8, 12 and 16 weeks after enrolment. The primary outcome variable was the Alzheimer Disease Assessment Scale-cognition (ADAS-Cog) score. Secondary outcomes were scores in the Mini-Mental State Examination (MMSE), the Activities of Daily Living (ADL) scale and the Clinical Global Impression (CGI) scale.
  
  
  RESULTS
  Sample sizes for the safety set (SS) analysis, full analysis set (FAS) and per protocol set (PPS) analysis were 112, 109 and 103 in the generic medication group, and 111, 107 and 101 in the proprietary medication group, respectively. The ADAS-Cog and ADL total scores at the end of weeks 4, 8, 12, and 16 decreased significantly compared with baseline for both groups (p<0.001) and the MMSE total scores at the end of weeks 4, 8, 12, and 16 increased significantly compared with baseline for both groups (p<0.001). There were no significant differences in ADAS-Cog total scores, ADL total scores and level of improvement based on the CGI scores between the two groups at any of the follow-up assessments. The occurrence of adverse events was 20.5% in the generic medication group and 27.0% in the proprietary medication group; this difference was not statistically significant (χ (2)=1.30, p=0.255).
  
  
  CONCLUSIONS
  There are no significant differences in the effectiveness or safety between memantine that is generically produced in China and imported proprietary memantine in the treatment of individuals with moderate and severe AD during the first 16 weeks of treatment.
authors.affiliation: Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine; Shanghai Diagnosis and Treatment Center for Alzheimer's disease, Shanghai, China.
authors.forename: Minjie
authors.initials: M
authors.lastname: Zhu
authors.affiliation: Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine; Shanghai Diagnosis and Treatment Center for Alzheimer's disease, Shanghai, China.
authors.forename: Shifu
authors.initials: S
authors.lastname: Xiao
authors.affiliation: Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine; Shanghai Diagnosis and Treatment Center for Alzheimer's disease, Shanghai, China.
authors.forename: Guanjun
authors.initials: G
authors.lastname: Li
authors.affiliation: Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine; Shanghai Diagnosis and Treatment Center for Alzheimer's disease, Shanghai, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Li
authors.affiliation: Guangzhou Psychiatric Hospital, Guangzhou, Guangdong Province, China.
authors.forename: Mouni
authors.initials: M
authors.lastname: Tang
authors.affiliation: First People's Hospital, Chenzhou, Hunan Province, China.
authors.forename: Siming
authors.initials: S
authors.lastname: Yang
authors.affiliation: First Affiliated Hospital of Kunming Medical School, Kunming, Yunnan Province, China.
authors.forename: Xiufeng
authors.initials: X
authors.lastname: Xu
authors.affiliation: The Chinese People's Liberation Army Bethune International Peace Hospital, Shijiazhuang, Hebei Province, China.
authors.forename: Lianyuan
authors.initials: L
authors.lastname: Feng
authors.affiliation: Affiliated Hospital of Guilin Medical School, Guilin, Guangxi Province, China.
authors.forename: Kaixiang
authors.initials: K
authors.lastname: Liu
authors.affiliation: Venturepharma Center of Data Management and Analysis, Beijing, China.
authors.forename: Lianping
authors.initials: L
authors.lastname: Hu