Effect of LY450139 on the Long Term Progression of Alzheimer's Disease
Status:
Completed
Trial end date:
2011-05-01
Target enrollment:
Participant gender:
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.