Double Blind Study of Trp01 in Patients With Alzheimer's Disease

Inclusion Criteria:

Patients will be selected in order to fulfill both of the following definitions:

• Dementia according to DSM-IV criteria :

  • development of multiple cognitive deficits manifested by both memory impairment and one or more of the following cognitive disturbances: aphasia, apraxia, agnosia, disturbance in executive functioning
  • the above-mentioned deficits cause significant impairment in social or occupational functioning
  • they do not occur exclusively during the course of delirium

• Dementia according to communicative disorders and stroke criteria (NINCDS-ADRDA)

  • dementia established clinically and documented by a Folstein Mini-Mental State Examination (MMSE)
  • deficits in two or more areas of cognition
  • progressive worsening of memory and other cognitive functions
  • no disturbance of consciousness
  • absence of systematic disorders or other brain diseases that in and of themselves can account for progressive deficit in memory and cognition

Furthermore, patients must fulfill the following criteria:

• men, or postmenopausal or surgically sterilized women
• with severity of dementia of mild to moderate degree as reflected by a score of greater than 14 but less than 26 on the MMSE
• with a minimum one-year duration of the symptomatology (progressive worsening of memory and other cognitive functions)
• living at home or in an institution provided that they have reliable caregivers
• able to perform the required psychometric tests and evaluations. Visual and auditory acuity (with glasses or hearing aid if required) must be sufficient to complete the protocol-specified procedures.
• Clinical laboratory battery (see section 7.2.2) must yield results within normal limits or determined as not clinically significant by the study physician for the patient’s sex and age
• Patients and their substitute decision-makers must have signed the written informed consent form

Exclusion Criteria:

Patients with any of the following will not be included in the study:

• Patients with any other cause of dementia as evidenced by medical history, general physical and neurological examination, laboratory tests, and neuroradiological findings:

  • Vascular dementia, as evidenced by Modified Hachinski Ischemia Scale
  • Depressive pseudementia, as evidenced by cognitive disturbances concomitant to a major depressive episode according to DSM-IV and/or a history of more than one major depressive episode
  • DSM-IV criteria for any major psychiatric disorder including schizophrenia, alcohol or substance abuse
  • Huntington’s chorea or Parkinson’s disease, evidenced by neurological examination, with an onset prior to or concurrent with dementia
  • Creutzfeldt-Jakob disease
  • Intracranial mass lesion
  • Clinically important head injury
  • History or current evidence of stroke
  • Onset of dementia following cardiac arrest or heart surgery
  • Neurosyphilis
  • Seropositivity for HIV
  • Vitamin B12 deficiency
  • Uncorrected hypothyroidism (i.e. abnormal free T4, ultrasensitive TSH)

• Patients with other relevant concomitant diseases:

  • Patients with history or current evidence of a sleep disorder
  • Patients with a clinically significant cardiovascular, renal, hepatic, pulmonary, gastrointestinal, endocrine, metabolic, opthalmologic, or hematologic condition
  • Current evidence or history within the past year of myocardial infarction (MI), congestive heart failure
  • Blood pressure at screening of > 180 mm Hg systolic or 100 mm Hg diastolic
  • Impaired renal, hepatic, or gastrointestinal function, which could interfere with drug absorption, metabolism or excretion
  • Seizure disorder
  • Diabetes
  • Earlier diagnosis or current evidence of cataracts
  • Progressive fatal disease (other than AD)
  • Treatment with any other investigational drug in the last 8 weeks prior to screening
  • Previous administration of TRP01