Effects of LY450139, on the Progression of Alzheimer's Disease as Compared With Placebo (IDENTITY-2)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT00762411
First received: September 26, 2008
Last updated: September 22, 2014
Last verified: September 2014
Results First Received: November 6, 2013  
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
Condition: Alzheimer's Disease
Interventions: Drug: LY450139
Drug: Placebo

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
140 mg LY450139 Participants received 60 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 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.

Participant Flow for 3 periods

Period 1:   Initial Treatment
    140 mg LY450139     Placebo  
STARTED     556     555  
Intent-to-treat (ITT)     555 [1]   553 [2]
COMPLETED     22     34  
NOT COMPLETED     534     521  
Death                 7                 6  
Adverse Event                 132                 40  
Protocol Violation                 4                 1  
Withdrawal by Subject                 65                 52  
Physician Decision                 1                 0  
Sponsor Decision                 293                 401  
Lost to Follow-up                 5                 0  
Caregiver Decision                 21                 16  
Abnormal Lab/ECG Result                 6                 4  
Entry Criteria Exclusion                 0                 1  
[1] ITT population included all randomized participants(pts) who received at least 1 dose of study drug.
[2] ITT population included all randomized participants who received at least 1 dose of study drug.

Period 2:   Delayed Start
    140 mg LY450139     Placebo  
STARTED     22     34  
COMPLETED     5     8  
NOT COMPLETED     17     26  
Adverse Event                 0                 4  
Protocol Violation                 0                 1  
Sponsor Decision                 16                 20  
Caregiver Decision                 1                 1  

Period 3:   Safety Follow Up (SFU)-Optional
    140 mg LY450139     Placebo  
STARTED     312 [1]   430 [1]
COMPLETED     228     312  
NOT COMPLETED     84     118  
Death                 1                 8  
Adverse Event                 0                 1  
Withdrawal by Subject                 21                 46  
Lost to Follow-up                 6                 1  
Caregiver Decision                 8                 8  
No safety visit or SFU                 48                 54  
[1] SFU was optional; pts entered from initial treatment and delayed start or did not enter SFU.



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
140 mg LY450139 Participants received 60 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 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.
Total Total of all reporting groups

Baseline Measures
    140 mg LY450139     Placebo     Total  
Number of Participants  
[units: participants]
  555     553     1108  
Age  
[units: years]
Mean ± Standard Deviation
  73.4  ± 8.0     73.0  ± 8.0     73.2  ± 8.0  
Gender  
[units: participants]
     
Female     316     327     643  
Male     239     226     465  
Race/Ethnicity, Customized  
[units: participants]
     
Caucasian     358     354     712  
African     11     8     19  
Hispanic     33     29     62  
East Asian     150     160     310  
West Asian     3     2     5  
Region of Enrollment  
[units: participants]
     
Brazil     18     21     39  
Bulgaria     20     18     38  
Canada     50     49     99  
China     22     22     44  
France     28     29     57  
Germany     24     20     44  
Hungary     19     16     35  
Italy     14     11     25  
Japan     64     69     133  
Korea, Republic of     38     43     81  
Mexico     26     24     50  
Romania     20     17     37  
Russian Federation     15     19     34  
Serbia     5     8     13  
Taiwan     25     24     49  
Turkey     25     23     48  
Ukraine     19     20     39  
United States     123     120     243  
Study-Specific Measure [1]
[units: units on a scale]
Mean ± Standard Deviation
  24.5  ± 9.1     24.2  ± 9.1     24.3  ± 9.1  
Study-Specific Measure [2]
[units: units on a scale]
Mean ± Standard Deviation
  58.8  ± 13.3     59.1  ± 13.8     58.9  ± 13.5  
[1] The cognitive subscale of the ADAS (ADAS‑Cog11) consists of 11 items assessing areas of function most typically impaired in AD: orientation, verbal memory, language, and praxis. The scale ranges from 0 to 70, with higher scores indicating greater disease severity.
[2] The Alzheimer's Disease Cooperative Study Activities of Daily Living (ADCS-ADL) Inventory Score is a 23-item inventory developed as a rater-administered questionnaire that should be answered by the participant’s caregiver. The ADCS-ADL measures both basic and instrumental activities of daily living by participants. The total ADCS-ADL score ranges from 0 to 78, with lower scores indicating greater disease severity.



  Outcome Measures
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1.  Primary:   Change From Baseline in Alzheimer's Disease Assessment Scale- Cognitive Subscale (ADAS-Cog11) at 76 Weeks   [ Time Frame: Baseline (randomization), 76 weeks ]

2.  Primary:   Change From Baseline in Alzheimer's Disease Assessment Scale- Cognitive Subscale (ADAS-Cog11) at 16 Weeks After Cessation of Study Drug   [ Time Frame: Baseline (randomization), 16 weeks following treatment cessation ]

3.  Primary:   Change From Baseline in Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory (ADCS-ADL) at 76 Weeks   [ Time Frame: Baseline (randomization), 76 weeks ]

4.  Primary:   Change From Baseline in Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory (ADCS-ADL) at 16 Weeks After Cessation of Study Drug   [ Time Frame: Baseline (randomization), 16 weeks following treatment cessation ]

5.  Secondary:   Change From Baseline in Clinical Dementia Rating (Sum of Boxes; CDR-SB) at 76 Weeks   [ Time Frame: Baseline (randomization), 76 weeks ]

6.  Secondary:   Change From Baseline in Neuropsychiatric Inventory (NPI) at 76 Weeks   [ Time Frame: Baseline (randomization), 76 weeks ]

7.  Secondary:   Change From Baseline in the Resource Utilization in Dementia-Lite (RUD-Lite) up to 76 Weeks   [ Time Frame: Baseline (randomization), up to 76 weeks ]

8.  Secondary:   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   [ Time Frame: Baseline (randomization), 76 weeks ]

9.  Secondary:   Change From Baseline in Quality of Life in Alzheimer's Disease (QoL-AD) at 76 Weeks   [ Time Frame: Baseline (randomization), 76 weeks ]

10.  Secondary:   Change From Baseline in Mini Mental State Examination (MMSE) at 76 Weeks   [ Time Frame: Baseline (randomization), 76 weeks ]

11.  Secondary:   Percent Change From Baseline in Amyloid Beta (Aβ) 1-42 Plasma Concentration at 52 Weeks   [ Time Frame: Baseline (randomization), 52 weeks ]

12.  Secondary:   Change From Baseline in Positron Emission Tomography (PET) Using Fluorine-18 Fluorodeoxyglucose (18F-FDG) at 76 Weeks   [ Time Frame: Baseline (randomization), 76 weeks ]

13.  Secondary:   Change From Baseline in Hippocampal Volume Using Volumetric Magnetic Resonance Imaging (vMRI) up to 76 Weeks   [ Time Frame: Baseline (randomization), up to 76 weeks ]

14.  Secondary:   Change From Baseline in Amyloid Imaging Positron Emission Tomography (AV-45 PET) up to 76 Weeks   [ Time Frame: Baseline (randomization), up to 76 weeks ]

15.  Secondary:   Change From Baseline in Tau Concentration in Spinal Fluid up to 76 Weeks   [ Time Frame: Baseline (randomization), up to 76 weeks ]

16.  Secondary:   LY450139 Population Pharmacokinetics: Clearance of LY450139   [ Time Frame: 6 weeks, 12 weeks, and 52 weeks ]

17.  Secondary:   LY450139 Population Pharmacokinetics: Volume of Distribution of LY450139   [ Time Frame: 6 weeks, 12 weeks, and 52 weeks ]

18.  Secondary:   Change From Baseline in Clinical Dementia Rating (Sum of Boxes; CDR-SB) at 4 Weeks After Cessation of Study Drug   [ Time Frame: Baseline (randomization), 4 weeks following treatment cessation ]

19.  Secondary:   Change From Baseline in Neuropsychiatric Inventory (NPI) at 4 Weeks After Cessation of Study Drug   [ Time Frame: Baseline (randomization), 4 weeks following treatment cessation ]

20.  Secondary:   Change From Baseline in Resource Utilization in Dementia-Lite (RUD-Lite) at 4 Weeks After Cessation of Study Drug   [ Time Frame: Baseline (randomization), 4 weeks following treatment cessation ]

21.  Secondary:   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   [ Time Frame: Baseline (randomization), 4 weeks following treatment cessation ]

22.  Secondary:   Change From Baseline in Quality of Life in Alzheimer's Disease (QoL-AD) at 4 Weeks After Cessation of Study Drug   [ Time Frame: Baseline (randomization), 4 weeks following treatment cessation ]

23.  Secondary:   Change From Baseline in Mini Mental State Examination (MMSE) 4 Weeks After Cessation of Study Drug   [ Time Frame: Baseline (randomization), 4 weeks following treatment cessation ]

24.  Secondary:   Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog12) at 76 Weeks   [ Time Frame: Baseline (randomization), 76 weeks ]

25.  Secondary:   Change From Baseline in Alzheimer's Disease Assessment Scale (ADAS-Cog14) at 76 Weeks   [ Time Frame: Baseline (randomization), 76 weeks ]

26.  Secondary:   Change From Baseline in Phosphorylated-Tau (P-tau) Concentration in Spinal Fluid up to 76 Weeks   [ Time Frame: Baseline (randomization), up to 76 weeks ]

27.  Secondary:   Change From Baseline in Amyloid Beta (Aβ) 1-42 Concentration in Spinal Fluid up to 76 Weeks   [ Time Frame: Baseline (randomization), up to 76 weeks ]

28.  Secondary:   Change From Baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog12) at 16 Weeks After Cessation of Study Drug   [ Time Frame: Baseline (randomization), 16 weeks following treatment cessation ]

29.  Secondary:   Change From Baseline in Alzheimer's Disease Assessment Scale (ADAS-Cog14) at 16 Weeks After Cessation of Study Drug   [ Time Frame: Baseline (randomization), 16 weeks following treatment cessation ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
All dosing for 4-week post-study drug cessation timeframe outcome measures stopped after protocol-specified interim review showed dose-dependent cognitive/functional worsening for LY450139 participants. No assessments made during 32-week follow up.


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.


Results Point of Contact:  
Name/Title: Chief Medical Officer
Organization: Eli Lilly and Company
phone: 800-545-5979


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
Results First Received: November 6, 2013
Last Updated: September 22, 2014
Health Authority: United States: Food and Drug Administration