Effects of LY450139, on the Progression of Alzheimer's Disease as Compared With Placebo - Full Text View

Sponsor:	Eli Lilly and Company
Information provided by (Responsible Party):	Eli Lilly and Company
ClinicalTrials.gov Identifier:	NCT00762411

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 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 lowers the production of beta amyloid. Semagacestat (LY450139) is a functional gamma-secretase inhibitor and was shown to lower beta 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 beta amyloid and amyloid plaques for some patients. 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 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 two 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 LFBC (and another similar study LFAN) 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 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.

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

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	Effect of LY450139 a y-Secretase Inhibitor, on the Progression of Alzheimer's Disease as Compared With Placebo

Resource links provided by NLM:

Genetics Home Reference related topics: Alzheimer disease

MedlinePlus related topics: Alzheimer's Disease Dementia

Drug Information available for: LY 450139

U.S. FDA Resources

Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:

Change in Alzheimer's Disease Assessment Scale - Cognition (ADAS-Cog11) during treatment [ Time Frame: Baseline (randomization), 12 weeks, 28 weeks, 40 weeks, 52 weeks, 64 weeks, and 76 weeks ] [ Designated as safety issue: No ]
Change in Alzheimer's Disease Assessment Scale - Cognition (ADAS-Cog11) after cessation of study drug [ Time Frame: Baseline (randomization); 4 weeks, 8weeks, 16 weeks, 32 weeks (following treatment cessation) ] [ Designated as safety issue: Yes ]
Change in Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory (ADCS-ADL) during treatment [ Time Frame: Baseline (randomization), 12 weeks, 28 weeks, 40 weeks, 52 weeks, 64 weeks, and 76 weeks ] [ Designated as safety issue: No ]
Change in Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory (ADCS-ADL) after cessation of study drug [ Time Frame: Baseline (randomization); 4 weeks, 8weeks, 16 weeks, 32 weeks (following treatment cessation) ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Change in Clinical Dementia Rating (Sum of Boxes) (CDR-SB) during Treatment [ Time Frame: Baseline (randomization), 28 weeks, 52 weeks, and 76 weeks ] [ Designated as safety issue: No ]
Change in Neuropsychiatric Inventory (NPI) during treatment [ Time Frame: Baseline (randomization), 28 weeks, 52 weeks, and 76 weeks ] [ Designated as safety issue: No ]
Change in Resource Utilization in Dementia - Lite Questionnaire (RUD-Lite) during treatment [ Time Frame: Baseline (randomization), 28 weeks, 52 weeks, and 76 weeks ] [ Designated as safety issue: No ]
Change in EuroQol 5-Dimensional Health-related Quality of Life scale (EQ-5D) during treatment [ Time Frame: Baseline (randomization), 28 weeks, 52 weeks, and 76 weeks ] [ Designated as safety issue: No ]
Change in Quality of Life in Alzheimer's Disease (Qol-AD) during treatment [ Time Frame: Baseline (randomization), 28 weeks, 52 weeks and 76 weeks ] [ Designated as safety issue: No ]
Change in Mini-mental State Examination (MMSE) during treatment [ Time Frame: Baseline (randomization), 52 weeks, and 76 weeks ] [ Designated as safety issue: No ]
Change in amyloid beta plasma concentration [ Time Frame: Baseline (randomization), 6 weeks, 12 weeks, 52 weeks, and 76 weeks ] [ Designated as safety issue: No ]
Change from baseline in positron emission tomography (PET) using fluorine- 18 fluorodeoxyglucose (FDG-PET) [ Time Frame: Baseline (randomization) and 76 weeks ] [ Designated as safety issue: No ]
Change from baseline in volumetric magnetic resonance imaging (vMRI) [ Time Frame: Baseline (randomization) and 76 weeks ] [ Designated as safety issue: No ]
Change from baseline in amyloid imaging positron emission tomography (AV-45) [ Time Frame: Baseline (randomization) and 76 weeks ] [ Designated as safety issue: No ]
Change in tau concentration in spinal fluid [ Time Frame: Baseline (randomization) and 76 weeks ] [ Designated as safety issue: No ]
Clearance and volume of distribution of LY450139 will be reported [ Time Frame: 6 weeks, 12 weeks, and 52 weeks ] [ Designated as safety issue: Yes ]
Change in Clinical Dementia Rating (Sum of Boxes) (CDR-SB) after cessation of study drug [ Time Frame: Baseline (randomization); 4 weeks (following treatment cessation) ] [ Designated as safety issue: Yes ]
Change in Neuropsychiatric Inventory (NPI) after cessation of study drug [ Time Frame: Baseline (randomization); 4 weeks (following treatment cessation) ] [ Designated as safety issue: Yes ]
Change in Resource Utilization in Dementia - Lite Questionnaire (RUD-Lite) after cessation of study drug [ Time Frame: Baseline (randomization); 4 weeks (following treatment cessation) ] [ Designated as safety issue: Yes ]
Change in EuroQol 5-Dimensional Health-related Quality of Life scale (EQ-5D) after cessation of study drug [ Time Frame: Baseline (randomization); 4 weeks (following treatment cessation) ] [ Designated as safety issue: Yes ]
Change in Quality of Life in Alzheimer's Disease (Qol-AD) after cessation of study drug [ Time Frame: Baseline (randomization); 4 weeks (following treatment cessation) ] [ Designated as safety issue: Yes ]
Change in Mini-mental State Examination (MMSE) after cessation of study drug [ Time Frame: Baseline (randomization); 4 weeks (following treatment cessation) ] [ Designated as safety issue: Yes ]
Change in Alzheimer's Disease Assessment Scale (ADAS-Cog12) during treatment [ Time Frame: Baseline (randomization), 12 weeks, 28 weeks, 40 weeks, 52 weeks, 64 weeks, and 76 weeks ] [ Designated as safety issue: No ]
Change in Alzheimer's Disease Assessment Scale (ADAS-Cog14) during treatment [ Time Frame: Baseline (randomization), 12 weeks, 28 weeks, 40 weeks, 52 weeks, 64 weeks, and 76 weeks ] [ Designated as safety issue: No ]
Change in phospho-tau concentration in spinal fluid [ Time Frame: Baseline (randomization) and 76 weeks ] [ Designated as safety issue: No ]
Change in amyloid beta 42 concentration in spinal fluid [ Time Frame: Baseline (randomization) and 76 weeks ] [ Designated as safety issue: No ]
Change in Alzheimer's Disease Assessment Scale (ADAS-Cog12) after cessation of study drug [ Time Frame: Baseline (randomization), 4 weeks, 8 weeks, 16 weeks, and 32 weeks (following treatment cessation) ] [ Designated as safety issue: Yes ]
Change in Alzheimer's Disease Assessment Scale (ADAS-Cog14) after cessation of study drug [ Time Frame: Baseline (randomization), 4 weeks, 8 weeks, 16 weeks, and 32 weeks (following treatment cessation) ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	1100
Study Start Date:	September 2008
Study Completion Date:	April 2011
Primary Completion Date:	April 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: LY450139	Drug: LY450139 60mg administered orally once daily, gradually escalated to 140 mg for the duration of the study Other Name: semagacestat
Placebo Comparator: Placebo	Drug: Placebo Administered orally once daily for the duration of the study

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 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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00762411

Show 91 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

No publications provided

Responsible Party:	Eli Lilly and Company
ClinicalTrials.gov Identifier:	NCT00762411 History of Changes
Other Study ID Numbers:	11271, H6L-MC-LFBC
Study First Received:	September 26, 2008
Last Updated:	August 22, 2011
Health Authority:	United States: Food and Drug Administration

Keywords provided by Eli Lilly and Company:

Alzheimer's Disease

Additional relevant MeSH terms:

Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases

Tauopathies
Neurodegenerative Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders

ClinicalTrials.gov processed this record on February 09, 2012