Effects of LY450139, on the Progression of Alzheimer's Disease as Compared With Placebo
Condition: Alzheimer's Disease
MeSH terms: Alzheimer Disease
Intervention: LY450139; Placebo
Intervention description: Administered orally once daily.; Administered orally once daily.
Intervention MeSH terms: N2-((2S)-2-(3,5-difluorophenyl)-2-hydroxyethanoyl)-N1-((7S)-5-methyl-6-oxo-6,7-dihydro-5H-dibenzo(b,d)azepin-7-yl)-L-alaninamide
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 1111.0
Sex: All
Minimum age: 55 Years
Healthy volunteers: No
Keywords: Alzheimer's Disease

Summary:

      Alzheimer's disease (AD) is a fatal degenerative disease of the brain for which there is no
      cure. AD causes brain cells to die. AD is thought to be caused by an excess of beta amyloid
      (β-amyloid), a sticky protein in the brain that forms amyloid plaques. At autopsy, AD
      patients are required to have these amyloid plaques in the brain in order to have a
      definitive diagnosis of AD. Inhibiting the enzyme gamma-secretase (γ-secretase) lowers the
      production of β-amyloid. Semagacestat (LY450139) is a functional γ-secretase inhibitor and
      was shown to lower β-amyloid in blood and spinal fluid in humans tested thus far and in
      blood, spinal fluid and brain in animals tested thus far. This study used several different
      tests to measure the effect of semagacestat on both β-amyloid and amyloid plaques for some
      patients. The buildup of amyloid plaques was measured by a brain scan that takes a picture of
      amyloid plaques in the brain. Other tests measured the overall function of the brain and
      brain size in some patients. In this trial, patients who initially received placebo (inactive
      sugar pill) were, at a certain point in the study, switched over to active drug,
      semagacestat. In other words, all patients could eventually receive active drug. Each
      patient's participation could last approximately 2 years. Patients taking approved AD
      medications were permitted to participate in this study and continue taking these medications
      during the study. All patients who completed this study had the option to continue receiving
      semagacestat by participating in an open label study.

      Preliminary results from this study (LFBC) (and another similar study LFAN [NCT00594568])
      showed semagacestat did not slow disease progression and was associated with worsening of
      clinical measures of cognition and the ability to perform activities of daily living. Study
      drug was stopped in all studies. LFBC, LFAN and open label LFBF (NCT01035138) have been
      amended to continue collecting safety data, including cognitive scores, for at least seven
      months. The CT-Registry will reflect results of analyses from the original protocol in
      addition to those from the amended protocol.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Meets criteria for mild to moderate Alzheimer's disease (AD) with Mini-Mental State
             Examination score of 16 through 26 at visit 1

          -  Modified Hachinski Ischemia Scale score of less than or equal to 4

          -  Geriatric Depression Scale score of less than or equal to 6

          -  A magnetic resonance imaging (MRI) or computerized tomography (CT) scan in the last 2
             years with no findings inconsistent with a diagnosis of AD

          -  If female, must be without menstruation for a least 12 consecutive months or have had
             both ovaries removed.

        Exclusion Criteria:

          -  Is not capable of swallowing whole oral medication

          -  Has serious or unstable illnesses

          -  Does not have a reliable caregiver

          -  Chronic alcohol and/or drug abuse within the past 5 years

          -  Has ever had a active vaccination for AD