Effect of LY450139 on the Long Term Progression of Alzheimer's Disease
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: 1537.0
Sex: All
Minimum age: 55 Years
Healthy volunteers: No

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
      participants. The build-up 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 participants. In this trial, participants 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 participants could eventually receive active drug.
      Participation could last approximately 2 years. Participants taking approved AD medications
      were permitted to participate in this study and continue taking these medications during the
      study. All participants who completed this study had the option to continue receiving
      semagacestat by participating in an open-label study.

      Preliminary results from this study (H6L-MC-LFAN [LFAN]) and another similar study
      (H6L-MC-LFBC [LFBC; NCT00762411]) 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. Studies LFAN, LFBC, and
      open-label H6L-MC-LFBF (LFBF; NCT01035138) were amended to continue collecting safety data,
      including cognitive scores, for at least 7 months. The Clinical Trial Registry (CTR) will
      reflect results of analyses from the original LFAN protocol in addition to those from the
      amended LFAN protocol.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Meets criteria for mild to moderate Alzheimer's disease (AD) with Mini-Mental State
             Examination (MMSE) score of 16-26 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 at 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 or drug abuse within the past 5 years

          -  Has ever had active vaccination for AD