Efficacy and Tolerability of MLC601 in Patients With Mild to Moderate Alzheimer Disease Who Were Unable to Tolerate or Failed to Benefit From Treatment With Rivastigmine

• changes in the Mini-Mental State Examination (MMSE) relative to baseline measurements [ Time Frame: every 4 weeks up to 18 months ] [ Designated as safety issue: No ]
  change in the Mini-Mental State Examination (MMSE) relative to baseline measurements will be evaluated every 4 weeks up to 18 months.
  
  
• changes in the cognitive subscale of the AD Assessment Scale (ADAS-cog) relative to baseline measurements [ Time Frame: every 4 weeks up to 18 months ] [ Designated as safety issue: No ]
  change in the cognitive subscale of the AD Assessment Scale (ADAS-cog) relative to baseline measurements will be evaluated every 4 weeks up to 18 months.
  
  

• to measure included adverse events (AEs) [ Time Frame: every 4 weeks ] [ Designated as safety issue: Yes ]
  Safety and tolerability evaluations included physical examinations, electrocardiography, vital sign monitoring and laboratory testing weekly for the first 8 weeks and every 4 weeks thereafter. AEs were defined as any sign, symptom, syndrome or disease that occurred for the first time or worsened after baseline, whether they were considered treatment related.
  
  
• measuring withdrawal rate [ Time Frame: every 4 weeks ] [ Designated as safety issue: Yes ]
  measuring any withdrawal rate among intervention group
  
  

An 18-month open-label pilot study would be conducted at three university referral centres in Tehran, Iran. All patients are at least 50 years old, met the criteria for AD according to the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV), and failed treatment with the cholinesterase inhibitor Rivastigmine for any reason. A baseline medical history will be taken and physical examination will be performed for all participants, and any comorbidities and concomitant therapies would be noted. Patients with controlled concomitant diseases, such as hypertension and diabetes, will be allowed to enter the study. Mini-Mental State Examination (MMSE)10 and Alzheimer disease assessment scale-cognitive sub scale11 (ADAS-cog) will be used to measure treatment efficacy. MLC601 will be prescribed as one capsule three times daily without an escalation dose. Safety and tolerability evaluations included physical examinations, electrocardiography, vital sign monitoring and laboratory testing weekly for the first 8 weeks and every 4 weeks thereafter. The MMSE and ADAS-cog will be recorded at each efficacy follow-up visit.