Effect of LY450139 on the Long Term Progression of Alzheimer's Disease - Full Text View

Purpose

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 A-Beta 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 inhibits the production of A-Beta amyloid as measured in blood and spinal fluid in humans tested thus far and in blood, spinal fluid and brain in animals tested thus far. This study will use several different tests to measure the effect of LY450139 on both A-Beta amyloid and amyloid plaques for some patients. The build up of amyloid plaques will be measured by a new brain scan that can take a picture of amyloid plaques in the brain. Other tests will attempt to measure the overall function of the brain and brain size in some patients. In this trial, patients who initially receive placebo (inactive sugar pill) will at a certain point in the study be switched over to active drug, LY450139. In other words, all patients will eventually receive active drug. Each patient's participation will last approximately two years. Patients taking approved AD medications may participate in this study and continue taking these medications during the study. All patients who complete this study will have the option to continue receiving LY450139 by participating in an open label study.

Condition	Intervention	Phase
Alzheimer's Disease	Drug: LY450139 Drug: placebo	Phase III

Genetics Home Reference related topics:

Alzheimer disease

MedlinePlus related topics:

Alzheimer's Disease Nuclear Scans

ChemIDplus related topics:

LY 450139

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study

Official Title:	Effect of γ-Secretase Inhibition on the Progression of Alzheimer's Disease: LY450139 Versus Placebo

Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:

Rate of cognitive and functional decline in Alzheimer's disease over time. [ Time Frame: Throughout the study ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Sometime during the study, patients originally given placebo will be given LY450139. This may help show the effect of long term treatment. [ Time Frame: Throughout the study ] [ Designated as safety issue: No ]
A chemical marker of AD in the blood which may be lowered by LY450139. [ Time Frame: Throughout the study ] [ Designated as safety issue: No ]
Energy usage (metabolism) seen on a brain scan called FDG-PET. [ Time Frame: Baseline and endpoint ] [ Designated as safety issue: No ]
Brain size (volume) seen with AD on a brain scan called vMRI. [ Time Frame: Baseline and endpoint ] [ Designated as safety issue: No ]
Amount of brain amyloid plaque seen in AD on a brain scan called AV-45-PET. [ Time Frame: Baseline and endpoint ] [ Designated as safety issue: No ]
A chemical marker (tau) known to be elevated in spinal fluid in AD. [ Time Frame: Baseline and endpoint ] [ Designated as safety issue: No ]
Safety [ Time Frame: Throughout the study ] [ Designated as safety issue: Yes ]
To measure levels of LY450139 and their effect on safety, chemical markers, and effectiveness. [ Time Frame: During the study ] [ Designated as safety issue: Yes ]
Quality of life. [ Time Frame: Throughout the study ] [ Designated as safety issue: No ]

Estimated Enrollment:	1500
Study Start Date:	March 2008
Estimated Study Completion Date:	March 2012
Estimated Primary Completion Date:	March 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental	Drug: LY450139 100 mg by mouth once a day for duration of study
2: Experimental	Drug: LY450139 140 mg by mouth once a day for duration of study
3: Placebo Comparator	Drug: placebo Once a day for a blinded period of time

Eligibility

Ages Eligible for Study:	55 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Meets criteria for mild to moderate 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 Alzheimer's disease
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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00594568

Contacts


Contact: There may be multiple sites in this clinical trial 1-877-CTLILLY (1-877-285-4559) or	1-317-615-4559

Show 59 Study Locations

Sponsors and Collaborators

Eli Lilly and Company

Investigators


Study Director:	Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours EST)	Eli Lilly and Company

More Information

Lilly Clinical Trial Registry This link exits the ClinicalTrials.gov site

Responsible Party:	Eli Lilly ( Chief Medical Officer )
Study ID Numbers:	7666, H6L-MC-LFAN
First Received:	January 11, 2008
Last Updated:	August 12, 2008
ClinicalTrials.gov Identifier:	NCT00594568
Health Authority:	United States: Food and Drug Administration

Study placed in the following topic categories:

Delirium, Dementia, Amnestic, Cognitive Disorders

Mental Disorders

Alzheimer Disease

Disease Progression

Central Nervous System Diseases

Neurodegenerative Diseases

Brain Diseases

Dementia

Cognition Disorders

Delirium

Additional relevant MeSH terms:

Nervous System Diseases

Tauopathies

ClinicalTrials.gov processed this record on August 28, 2008

Sponsored by:	Eli Lilly and Company
Information provided by:	Eli Lilly and Company
ClinicalTrials.gov Identifier:	NCT00594568