Trial record 1 of 1 for:    NCT00594568
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Effect of LY450139 on the Long Term Progression of Alzheimer's Disease

This study has been completed.
Sponsor:
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

January 11, 2008
August 9, 2011
March 2008
May 2011   (final data collection date for primary outcome measure)
  • 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 ]
Rate of cognitive and functional decline in Alzheimer's disease over time. [ Time Frame: Throughout the study ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00594568 on ClinicalTrials.gov Archive Site
  • 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 ]
  • 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 PIB-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 ]
Not Provided
Not Provided
 
Effect of LY450139 on the Long Term Progression of Alzheimer's Disease
Effect of γ-Secretase Inhibition on the Progression of Alzheimer's Disease: LY450139 Versus Placebo

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.

Not Provided
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Alzheimer's Disease
  • Drug: LY450139
    Administered orally once daily for duration of study
    Other Name: semagacestat
  • Drug: placebo
    Administered orally once daily for duration of study
  • Experimental: 100 mg LY450139
    Intervention: Drug: LY450139
  • Experimental: 140 mg LY450139
    Intervention: Drug: LY450139
  • Placebo Comparator: Placebo
    Intervention: Drug: placebo
Doody RS, Raman R, Farlow M, Iwatsubo T, Vellas B, Joffe S, Kieburtz K, He F, Sun X, Thomas RG, Aisen PS; Alzheimer's Disease Cooperative Study Steering Committee, Siemers E, Sethuraman G, Mohs R; Semagacestat Study Group. A phase 3 trial of semagacestat for treatment of Alzheimer's disease. N Engl J Med. 2013 Jul 25;369(4):341-50. doi: 10.1056/NEJMoa1210951.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
164
May 2011
May 2011   (final data collection date for primary outcome measure)

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
Both
55 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Argentina,   Australia,   Belgium,   Canada,   Chile,   Denmark,   Finland,   France,   Germany,   India,   Israel,   Italy,   Japan,   Poland,   South Africa,   Spain,   Sweden,   United Kingdom
 
NCT00594568
7666, H6L-MC-LFAN, CTRI/2009/091/000090
Yes
Chief Medical Officer, Eli Lilly
Eli Lilly and Company
Not Provided
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
Eli Lilly and Company
July 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP