Trial record 1 of 5 for:
LY-450139 alzheimer
Effect of LY450139 on the Long Term Progression of Alzheimer's Disease
This study has been completed.
Sponsor:
Eli Lilly and Company
Information provided by:
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT00594568
First received: January 11, 2008
Last updated: August 9, 2011
Last verified: July 2011
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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 LFAN (and another similar study LFBC) 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. LFAN, LFBC 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 3 |
| 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 γ-Secretase Inhibition on the Progression of Alzheimer's Disease: LY450139 Versus Placebo |
Resource links provided by NLM:
Further study details as provided by Eli Lilly and Company:
Primary Outcome Measures:
- Change in Alzheimer's Disease Assessment Scale-Cognitive subscale (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-Cognitive subscale (ADAS-Cog11) after cessation of study drug [ Time Frame: Baseline (randomization); 4 weeks, 8 weeks, 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, 8 weeks, 16 weeks, 32 weeks (following treatment cessation) ] [ Designated as safety issue: Yes ]
Secondary Outcome Measures:
- A 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 ]
- A 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 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 Clinical Dementia Rating (Sum of Boxes) (CDR-SB) 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 Neuropsychiatric Inventory (NPI) 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 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 Resource Utilization in Dementia-Lite (RUD-Lite) during treatment [ Time Frame: Baseline (randomization), 28 weeks, 52 weeks and 76 weeks ] [ Designated as safety issue: No ]
- Change in Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog12) after cessation of study drug [ Time Frame: Baseline (randomization); 4 weeks, 8 weeks, 16 weeks, 32 weeks (following treatment cessation) ] [ Designated as safety issue: Yes ]
- Change in Alzheimer's Disease Assessment Scale (ADAS-Cog 14) after cessation of study drug [ Time Frame: Baseline (randomization); 4 weeks, 8 weeks, 16 weeks, 32 weeks (following treatment cessation) ] [ Designated as safety issue: Yes ]
- Change in Clinical Dementia Rating (Sum of the 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 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 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 Resource Utilization in Dementia-Lite (RUD-Lite) after cessation of study drug [ Time Frame: Baseline (randomization); 4 weeks (following treatment cessation) ] [ Designated as safety issue: Yes ]
- A change in phospho-tau concentration in spinal fluid [ Time Frame: Baseline (randomization) and 76 weeks ] [ Designated as safety issue: No ]
- A change in amyloid beta 42 concentration in spinal fluid [ Time Frame: Baseline (randomization) and 76 weeks ] [ Designated as safety issue: No ]
| Enrollment: | 164 |
| Study Start Date: | March 2008 |
| Study Completion Date: | May 2011 |
| Primary Completion Date: | May 2011 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
| Experimental: 100 mg LY450139 |
Drug: LY450139
Administered orally once daily for duration of study
Other Name: semagacestat
|
| Experimental: 140 mg LY450139 |
Drug: LY450139
Administered orally once daily for duration of study
Other Name: semagacestat
|
| Placebo Comparator: Placebo |
Drug: placebo
Administered orally once daily for duration of 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 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
Show 148 Study Locations
Show 148 Study LocationsSponsors 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
Additional Information:
No publications provided
| Responsible Party: | Chief Medical Officer, Eli Lilly |
| ClinicalTrials.gov Identifier: | NCT00594568 History of Changes |
| Other Study ID Numbers: | 7666, H6L-MC-LFAN, CTRI/2009/091/000090 |
| Study First Received: | January 11, 2008 |
| Last Updated: | August 9, 2011 |
| Health Authority: | United States: Food and Drug Administration Argentina: Ministry of Health Australia: Department of Health and Ageing Therapeutic Goods Administration Belgium: Federal Agency for Medicinal Products and Health Products Canada: Health Canada Chile: Ministry of Health Denmark: Danish Medicines Agency Finland: Finnish Medicines Agency France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis) Germany: Federal Institute for Drugs and Medical Devices Germany: Federal Office for Radiation Protection India: Drugs Controller General of India Israel: Ministry of Health Italy: The Italian Medicines Agency Japan: Ministry of Health, Labor and Welfare Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products South Africa: Department of Health Spain: Agencia Española de Medicamentos y Productos Sanitarios Sweden: Medical Products Agency United Kingdom: Medicines and Healthcare Products Regulatory Agency |
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 May 23, 2013