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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT00762411




Registration number
NCT00762411
Ethics application status
Date submitted
26/09/2008
Date registered
30/09/2008
Date last updated
16/02/2015

Titles & IDs
Public title
Effects of LY450139, on the Progression of Alzheimer's Disease as Compared With Placebo
Scientific title
Effect of LY450139 a y-Secretase Inhibitor, on the Progression of Alzheimer's Disease as Compared With Placebo
Secondary ID [1] 0 0
H6L-MC-LFBC
Secondary ID [2] 0 0
11271
Universal Trial Number (UTN)
Trial acronym
IDENTITY-2
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Alzheimer's Disease 0 0
Condition category
Condition code
Neurological 0 0 0 0
Alzheimer's disease
Neurological 0 0 0 0
Dementias

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - LY450139
Treatment: Drugs - Placebo

Experimental: LY450139 - Participants received 60 milligrams (mg) LY450139 orally once daily for 2 weeks followed by 100 mg LY450139 orally once daily for 2 weeks, then 140 mg LY450139 orally once daily until Week 88.

Placebo Comparator: Placebo - Participants received placebo orally once daily for the first 76 weeks. At the end of 76 weeks, participants in the placebo arm received LY450139 titrated up to 140 mg orally once daily until Week 88.


Treatment: Drugs: LY450139
Administered orally once daily.

Treatment: Drugs: Placebo
Administered orally once daily.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change From Baseline in Alzheimer's Disease Assessment Scale- Cognitive Subscale (ADAS-Cog11) at 76 Weeks
Timepoint [1] 0 0
Baseline (randomization), 76 weeks
Primary outcome [2] 0 0
Change From Baseline in Alzheimer's Disease Assessment Scale- Cognitive Subscale (ADAS-Cog11) at 16 Weeks After Cessation of Study Drug
Timepoint [2] 0 0
Baseline (randomization), 16 weeks following treatment cessation
Primary outcome [3] 0 0
Change From Baseline in Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory (ADCS-ADL) at 76 Weeks
Timepoint [3] 0 0
Baseline (randomization), 76 weeks
Primary outcome [4] 0 0
Change From Baseline in Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory (ADCS-ADL) at 16 Weeks After Cessation of Study Drug
Timepoint [4] 0 0
Baseline (randomization), 16 weeks following treatment cessation
Secondary outcome [1] 0 0
Change From Baseline in Clinical Dementia Rating Sum of Boxes (CDR-SB) at 76 Weeks
Timepoint [1] 0 0
Baseline (randomization), 76 weeks
Secondary outcome [2] 0 0
Change From Baseline in Neuropsychiatric Inventory (NPI) at 76 Weeks
Timepoint [2] 0 0
Baseline (randomization), 76 weeks
Secondary outcome [3] 0 0
Change From Baseline in the Resource Utilization in Dementia-Lite (RUD-Lite) up to 76 Weeks
Timepoint [3] 0 0
Baseline (randomization), up to 76 weeks
Secondary outcome [4] 0 0
Change From Baseline in the EuroQol 5-Dimensional Health-Related Quality of Life Scale Proxy Version (EQ-5D Proxy) Visual Analog Scale (VAS) at 76 Weeks
Timepoint [4] 0 0
Baseline (randomization), 76 weeks
Secondary outcome [5] 0 0
Change From Baseline in Quality of Life in Alzheimer's Disease (QoL-AD) at 76 Weeks
Timepoint [5] 0 0
Baseline (randomization), 76 weeks
Secondary outcome [6] 0 0
Change From Baseline in Mini Mental State Examination (MMSE) at 76 Weeks
Timepoint [6] 0 0
Baseline (randomization), 76 weeks
Secondary outcome [7] 0 0
Percent Change From Baseline in Amyloid Beta (Aß) 1-42 Plasma Concentration at 52 Weeks
Timepoint [7] 0 0
Baseline (randomization), 52 weeks
Secondary outcome [8] 0 0
Change From Baseline in Positron Emission Tomography (PET) Using Fluorine-18 Fluorodeoxyglucose (18F-FDG) at 76 Weeks
Timepoint [8] 0 0
Baseline (randomization), 76 weeks
Secondary outcome [9] 0 0
Change From Baseline in Hippocampal Volume Using Volumetric Magnetic Resonance Imaging (vMRI) up to 76 Weeks
Timepoint [9] 0 0
Baseline (randomization), up to 76 weeks
Secondary outcome [10] 0 0
Change From Baseline in Amyloid Imaging Positron Emission Tomography (AV-45 PET) up to 76 Weeks
Timepoint [10] 0 0
Baseline (randomization), up to 76 weeks
Secondary outcome [11] 0 0
Change From Baseline in Tau Concentration in Spinal Fluid up to 76 Weeks
Timepoint [11] 0 0
Baseline (randomization), up to 76 weeks
Secondary outcome [12] 0 0
LY450139 Population Pharmacokinetics: Clearance of LY450139
Timepoint [12] 0 0
6 weeks, 12 weeks, and 52 weeks
Secondary outcome [13] 0 0
LY450139 Population Pharmacokinetics: Volume of Distribution of LY450139
Timepoint [13] 0 0
6 weeks, 12 weeks, and 52 weeks
Secondary outcome [14] 0 0
Change From Baseline in Clinical Dementia Rating Sum of Boxes (CDR-SB) at 4 Weeks After Cessation of Study Drug
Timepoint [14] 0 0
Baseline (randomization), 4 weeks following treatment cessation
Secondary outcome [15] 0 0
Change From Baseline in Neuropsychiatric Inventory (NPI) at 4 Weeks After Cessation of Study Drug
Timepoint [15] 0 0
Baseline (randomization), 4 weeks following treatment cessation
Secondary outcome [16] 0 0
Change From Baseline in Resource Utilization in Dementia-Lite (RUD-Lite) at 4 Weeks After Cessation of Study Drug
Timepoint [16] 0 0
Baseline (randomization), 4 weeks following treatment cessation
Secondary outcome [17] 0 0
Change From Baseline in EuroQol 5-Dimensional Health-Related Quality of Life Scale Proxy Version (EQ-5D Proxy) Visual Analog Scale (VAS) at 4 Weeks After Cessation of Study Drug
Timepoint [17] 0 0
Baseline (randomization), 4 weeks following treatment cessation
Secondary outcome [18] 0 0
Change From Baseline in Quality of Life in Alzheimer's Disease (QoL-AD) at 4 Weeks After Cessation of Study Drug
Timepoint [18] 0 0
Baseline (randomization), 4 weeks following treatment cessation
Secondary outcome [19] 0 0
Change From Baseline in Mini Mental State Examination (MMSE) 4 Weeks After Cessation of Study Drug
Timepoint [19] 0 0
Baseline (randomization), 4 weeks following treatment cessation
Secondary outcome [20] 0 0
Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog12) at 76 Weeks
Timepoint [20] 0 0
Baseline (randomization), 76 weeks
Secondary outcome [21] 0 0
Change From Baseline in Alzheimer's Disease Assessment Scale (ADAS-Cog14) at 76 Weeks
Timepoint [21] 0 0
Baseline (randomization), 76 weeks
Secondary outcome [22] 0 0
Change From Baseline in Phosphorylated-Tau (P-tau) Concentration in Spinal Fluid up to 76 Weeks
Timepoint [22] 0 0
Baseline (randomization), up to 76 weeks
Secondary outcome [23] 0 0
Change From Baseline in Amyloid Beta (Aß) 1-42 Concentration in Spinal Fluid up to 76 Weeks
Timepoint [23] 0 0
Baseline (randomization), up to 76 weeks
Secondary outcome [24] 0 0
Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog12) at 16 Weeks After Cessation of Study Drug
Timepoint [24] 0 0
Baseline (randomization), 16 weeks following treatment cessation
Secondary outcome [25] 0 0
Change From Baseline in Alzheimer's Disease Assessment Scale (ADAS-Cog14) at 16 Weeks After Cessation of Study Drug
Timepoint [25] 0 0
Baseline (randomization), 16 weeks following treatment cessation

Eligibility
Key inclusion criteria
- Meets criteria for mild to moderate Alzheimer's disease (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.
Minimum age
55 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/09/2008
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/04/2011
Sample size
Target
Accrual to date
Final
1111
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Louisiana
Country [5] 0 0
United States of America
State/province [5] 0 0
Mississippi
Country [6] 0 0
United States of America
State/province [6] 0 0
Nebraska
Country [7] 0 0
United States of America
State/province [7] 0 0
New York
Country [8] 0 0
United States of America
State/province [8] 0 0
North Carolina
Country [9] 0 0
United States of America
State/province [9] 0 0
Oklahoma
Country [10] 0 0
United States of America
State/province [10] 0 0
Pennsylvania
Country [11] 0 0
Brazil
State/province [11] 0 0
Rio De Janeiro
Country [12] 0 0
Brazil
State/province [12] 0 0
Salvador
Country [13] 0 0
Brazil
State/province [13] 0 0
São Paulo
Country [14] 0 0
Bulgaria
State/province [14] 0 0
Sofia
Country [15] 0 0
Canada
State/province [15] 0 0
Manitoba
Country [16] 0 0
Canada
State/province [16] 0 0
New Brunswick
Country [17] 0 0
Canada
State/province [17] 0 0
Ontario
Country [18] 0 0
Canada
State/province [18] 0 0
Quebec
Country [19] 0 0
China
State/province [19] 0 0
Beijing
Country [20] 0 0
China
State/province [20] 0 0
Shanghai
Country [21] 0 0
China
State/province [21] 0 0
Xi'An
Country [22] 0 0
France
State/province [22] 0 0
Montpellier
Country [23] 0 0
France
State/province [23] 0 0
Paris
Country [24] 0 0
France
State/province [24] 0 0
Poitiers
Country [25] 0 0
France
State/province [25] 0 0
Strasbourg
Country [26] 0 0
Germany
State/province [26] 0 0
Berlin
Country [27] 0 0
Germany
State/province [27] 0 0
Frankfurt
Country [28] 0 0
Germany
State/province [28] 0 0
Hamburg
Country [29] 0 0
Germany
State/province [29] 0 0
Heidelberg
Country [30] 0 0
Germany
State/province [30] 0 0
Mannheim
Country [31] 0 0
Hungary
State/province [31] 0 0
Budapest
Country [32] 0 0
Hungary
State/province [32] 0 0
Esztergom
Country [33] 0 0
Italy
State/province [33] 0 0
Boggiovara
Country [34] 0 0
Italy
State/province [34] 0 0
Cassino
Country [35] 0 0
Italy
State/province [35] 0 0
Milano
Country [36] 0 0
Italy
State/province [36] 0 0
Parma
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Japan
State/province [37] 0 0
Akita
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Japan
State/province [38] 0 0
Fukuoka
Country [39] 0 0
Japan
State/province [39] 0 0
Hyogo
Country [40] 0 0
Japan
State/province [40] 0 0
Ibaraki
Country [41] 0 0
Japan
State/province [41] 0 0
Iwate
Country [42] 0 0
Japan
State/province [42] 0 0
Kanagawa
Country [43] 0 0
Japan
State/province [43] 0 0
Kumamoto
Country [44] 0 0
Japan
State/province [44] 0 0
Kyoto
Country [45] 0 0
Japan
State/province [45] 0 0
Nagasaki
Country [46] 0 0
Japan
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Osaka
Country [47] 0 0
Japan
State/province [47] 0 0
Saitama
Country [48] 0 0
Japan
State/province [48] 0 0
Tokyo
Country [49] 0 0
Korea, Republic of
State/province [49] 0 0
Seoul
Country [50] 0 0
Korea, Republic of
State/province [50] 0 0
Suwon
Country [51] 0 0
Mexico
State/province [51] 0 0
Aguascalientes
Country [52] 0 0
Mexico
State/province [52] 0 0
Monterrey
Country [53] 0 0
Mexico
State/province [53] 0 0
Saltillo
Country [54] 0 0
Romania
State/province [54] 0 0
Bucharest
Country [55] 0 0
Romania
State/province [55] 0 0
Timisoara
Country [56] 0 0
Russian Federation
State/province [56] 0 0
Ekaterinburg
Country [57] 0 0
Russian Federation
State/province [57] 0 0
Kazan
Country [58] 0 0
Russian Federation
State/province [58] 0 0
Saint Petersburg
Country [59] 0 0
Russian Federation
State/province [59] 0 0
Saratov
Country [60] 0 0
Serbia
State/province [60] 0 0
Belgrade
Country [61] 0 0
Serbia
State/province [61] 0 0
Kragujevac
Country [62] 0 0
Taiwan
State/province [62] 0 0
Changhua
Country [63] 0 0
Taiwan
State/province [63] 0 0
Tainan
Country [64] 0 0
Taiwan
State/province [64] 0 0
Taipei
Country [65] 0 0
Taiwan
State/province [65] 0 0
Tao-Yuan
Country [66] 0 0
Turkey
State/province [66] 0 0
Eskisehir
Country [67] 0 0
Turkey
State/province [67] 0 0
Istanbul
Country [68] 0 0
Turkey
State/province [68] 0 0
Izmir
Country [69] 0 0
Turkey
State/province [69] 0 0
Samsun
Country [70] 0 0
Ukraine
State/province [70] 0 0
Dnipropetrovsk
Country [71] 0 0
Ukraine
State/province [71] 0 0
Donetsk
Country [72] 0 0
Ukraine
State/province [72] 0 0
Kherson
Country [73] 0 0
Ukraine
State/province [73] 0 0
Kyiv
Country [74] 0 0
Ukraine
State/province [74] 0 0
Odesa

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Eli Lilly and Company
Address
Country

Ethics approval
Ethics application status

Summary
Brief 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
(ß-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 (?-secretase) lowers the
production of ß-amyloid. Semagacestat (LY450139) is a functional ?-secretase inhibitor and
was shown to lower ß-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 ß-amyloid and amyloid plaques for some
patients. The buildup 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 2 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 this study (LFBC) (and another similar study LFAN [NCT00594568])
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 (NCT01035138) 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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT00762411
Trial related presentations / publications
Public notes
This record is viewable in the ANZCTR as it had previously listed Australia and/or New Zealand as a recruitment site, however these sites have since been removed

Contacts
Principal investigator
Name 0 0
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)
Address 0 0
Eli Lilly and Company
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries