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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01035138




Trial ID
NCT01035138
Ethics application status
Date submitted
17/12/2009
Date registered
17/12/2009
Date last updated
22/09/2014

Titles & IDs
Public title
A Study of Semagacestat for Alzheimer's Patients
Scientific title
Open-Label Extension for Alzheimer's Disease Patients Who Complete One of Two Semagacestat Phase 3 Double-Blind Studies (H6L-MC-LFAN or H6L-MC-LFBC)
Secondary ID [1] 0 0
H6L-MC-LFBF
Secondary ID [2] 0 0
5930
Universal Trial Number (UTN)
Trial acronym
Identity XT
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 - semagacestat

Experimental: Drug: semagacestat -


Treatment: Drugs: semagacestat
140mg administered orally, once daily for 24 months; dose reduction to 100mg or 60 mg possible due to intolerability

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 Week 16 After Cessation of Study Drug - The cognitive subscale of the ADAS (ADAS-Cog11) consists of 11 items assessing areas of function most typically impaired in Alzheimer's Disease (AD): orientation, verbal memory, language, and praxis. The scale ranges from 0 to 70, with higher scores indicating greater disease severity.
Timepoint [1] 0 0
Baseline (LFAN randomization), 16 weeks (LFBF) after cessation of study drug
Primary outcome [2] 0 0
Change From Baseline in Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory (ADCS-ADL) at Week 16 After Cessation of Study Drug - The ADCS-ADL is a 23-item inventory developed as a rater-administered questionnaire answered by the participant's caregiver. It measures both basic and instrumental activities of daily living. The total score ranges from 0 to 78, with lower scores indicating greater disease severity.
Timepoint [2] 0 0
Baseline (LFAN randomization), 16 weeks (LFBF) after cessation of study drug
Secondary outcome [1] 0 0
Percent Change From Baseline in Amyloid Beta (Aß) 1-42 Plasma Concentration at Week 12 - Concentration of amino acid peptide known as Aß 1-42 in plasma. Least Square (LS) Mean value was controlled for baseline value, age, and investigator.
Timepoint [1] 0 0
Baseline (LFAN Randomization ), 6 hours pose-dose at Week 12 (LFBF)
Secondary outcome [2] 0 0
Change From Baseline in Hippocampal Volume Using Volumetric Magnetic Resonance Imaging (vMRI) at Week 12 - The vMRI assessment of right hippocampal and left hippocampal volume is reported. Least Square (LS) Mean value was controlled for baseline value, age, and investigator.
Timepoint [2] 0 0
Baseline (LFAN Randomization), 12 weeks (LFBF)
Secondary outcome [3] 0 0
Change From Baseline in Amyloid Imaging Positron Emission Tomography (AV-45-PET) at Week 12 - A radioactive tracer for PET that is a ligand for amyloid called [18F]-AV-45. This permits the visualization of amyloid in the brains of Alzheimer's participants. The outcome reported is the composite summary of the standard uptake value ratio for the cerebellar gray matter. Least Squares (LS) Mean value was controlled for baseline value, age, and investigator. Due to insufficient sample size, this analysis was not done.
Timepoint [3] 0 0
Baseline (LFAN Randomization), 12 weeks (LFBF)
Secondary outcome [4] 0 0
Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog11) at Week 12 - The cognitive subscale of the ADAS (ADAS-Cog11) consists of 11 items assessing areas of function most typically impaired in Alzheimer's Disease (AD): orientation, verbal memory, language, and praxis. The scale ranges from 0 to 70, with higher scores indicating greater disease severity. Least Square (LS) Mean value was controlled for baseline value, age, investigator, and concomitant standard of care (SOC) medication.
Timepoint [4] 0 0
Baseline (LFAN Randomization), 12 weeks (LFBF)
Secondary outcome [5] 0 0
Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog12) at Week 12 - ADAS-Cog12 is the ADAS-Cog11 augmented with the delayed free recall measure, resulting in a total score ranging from 0 to 80. Higher scores indicate greater disease severity. Least Square (LS) Mean value was controlled for baseline value, age, investigator, and concomitant standard of care (SOC) medication.
Timepoint [5] 0 0
Baseline (LFAN Randomization), 12 weeks (LFBF)
Secondary outcome [6] 0 0
Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog14) at Week 12 - The ADAS-Cog14 is the ADAS-Cog11 augmented with delayed free recall, digit cancellation, and maze completion measures. A score of 0 to 10 for delayed free recall and a conversion code of 0 to 5 for digit cancellation and maze completion provide total score ranges for this extended ADAS-Cog14 of 0 to 90. Higher scores indicate greater disease severity. Least Square (LS) Mean value was controlled for the baseline value, age, investigator, and concomitant standard of care (SOC) medication.
Timepoint [6] 0 0
Baseline (LFAN Randomization), 12 weeks (LFBF)
Secondary outcome [7] 0 0
Change From Baseline in Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory (ADCS-ADL) at Week 12 - The ADCS-ADL is a 23-item inventory developed as a rater-administered questionnaire answered by the participant's caregiver. It measures both basic and instrumental activities of daily living. The total score ranges from 0 to 78, with lower scores indicating greater disease severity. Least Square (LS) Mean value was controlled for baseline value, age, investigator, and concomitant standard of care (SOC) medication.
Timepoint [7] 0 0
Baseline (LFAN Randomization), 12 weeks (LFBF)
Secondary outcome [8] 0 0
Mean Concentration of LY450139
Timepoint [8] 0 0
3 months (pre-dose, 2, 4, and 6 hours after dosing )(LFBF)
Secondary outcome [9] 0 0
Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog12) at Week 16 After Cessation of Study Drug - ADAS-Cog12 is the ADAS-Cog11 augmented with the delayed free recall measure, resulting in a total score ranging from 0 to 80. Higher scores indicate greater disease severity.
Timepoint [9] 0 0
Baseline (LFAN Randomization), 16 weeks (LFBF) after cessation of study drug
Secondary outcome [10] 0 0
Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog14) at Week 16 After Cessation of Study Drug - The ADAS-Cog14 is the ADAS-Cog11 augmented with delayed free recall, digit cancellation, and maze completion measures. A score of 0 to 10 for delayed free recall and a conversion code of 0 to 5 for digit cancellation and maze completion provide total score ranges for this extended ADAS-Cog14 of 0 to 90. Higher scores indicate greater disease severity.
Timepoint [10] 0 0
Baseline (LFAN Randomization), 16 weeks (LFBF) after cessation of study drug
Secondary outcome [11] 0 0
Change From Baseline in Clinical Dementia Rating Scale (Sum of Boxes) (CDR-SB) at Week 24 - The CDR-SB is a semi-structured interview of participants and their caregivers. The participant's cognitive status is rated in 6 domains of functioning, including memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care. A severity score is assigned for each of the 6 domains with total score ranging from 0 to 18. Higher scores indicate greater disease severity. Least Square (LS) Mean value was controlled for baseline value, age, investigator, and concomitant standard of care (SOC) medication.
Timepoint [11] 0 0
Baseline (LFAN Randomization), 24 weeks (LFBF)
Secondary outcome [12] 0 0
Change From Baseline in Mini-Mental State Examination (MMSE) at Week 24 - The MMSE is a brief screening instrument used to assess cognitive function in elderly participants. It assesses orientation, memory, attention, and ability to name objects, follow verbal and written commands, write a sentence, and copy figures. The total score ranges from 0 to 30, with a lower score indicating greater disease severity. Least Square (LS) Mean value was controlled for baseline value, age, investigator, and concomitant standard of care (SOC) medication.
Timepoint [12] 0 0
Baseline (LFAN Randomization), 24 weeks (LFBF)
Secondary outcome [13] 0 0
Change From Baseline in Neuropsychiatric Inventory (NPI) at Week 24 - The NPI is a tool for assessing psychopathology in patients with dementia and other neurologic disorders. Information is obtained from a caregiver familiar with the patient's behavior. The score ranges from 12 to 144, with higher scores indicating greater disease severity. Least Square (LS) Mean value was controlled for the baseline value, age, investigator, concomitant standard of care medication.
Timepoint [13] 0 0
Baseline (LFAN Randomization), 24 weeks (LFBF)
Secondary outcome [14] 0 0
Change From Baseline in EuroQol-5D (EQ-5D) at Week 24 - EQ-5D (proxy version) measures mobility, self-care, usual activities, pain/discomfort, anxiety/depression; each has 3 severity levels (no, some, severe problems) coded to a 1-digit number (1-3). Digits are combined into 5-digit number describing health state. Numbers 1-3 are not added for total score. Visual Analog Scale (VAS) assesses caregiver's impression of participant's overall health state; VAS scores range=0-100, with lower scores indicating greater disease severity. LS Mean value was controlled for baseline value, age, investigator, and concomitant standard of care (SOC) medication.
Timepoint [14] 0 0
Baseline (LFAN Randomization), 24 weeks (LFBF)
Secondary outcome [15] 0 0
Change From Baseline in Resource Utilization in Dementia-Lite Questionnaire (RUD-Lite) at Week 12 - RUD-Lite assesses the healthcare resource utilization of participants and their caregivers to determine the level of formal and informal care attributable to Alzheimer's Disease (AD). Information on both caregivers (caregiving time, work status) and participants (accommodation and healthcare resource utilization) is collected from the baseline and follow-up interviews. Reported the change in number of hospitalizations per participant to week 12.
Timepoint [15] 0 0
Baseline (LFAN Randomization), 12 weeks (LFBF)

Eligibility
Key inclusion criteria
- Meets National Institute of Neurological and Communicative Disorders and
Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS/ADRDA) criteria
for probable Alzheimer's Disease

- Completed semagacestat study LFAN or study LFBC through 88 weeks

- Must continue to have a reliable caregiver

- Capable of swallowing whole oral medication

- Agrees not to participate in other investigational compounds for the duration of study
Minimum age
55 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Meets LFAN or LFBC study discontinuation criteria at the last visit of the LFAN or
LFBC study

Study design
Purpose of the study
Treatment
Allocation to intervention
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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
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
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. - Kogarah
Recruitment hospital [2] 0 0
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. - Geelong
Recruitment hospital [3] 0 0
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. - Heidelberg West
Recruitment postcode(s) [1] 0 0
2217 - Kogarah
Recruitment postcode(s) [2] 0 0
3220 - Geelong
Recruitment postcode(s) [3] 0 0
3081 - Heidelberg West
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
Connecticut
Country [4] 0 0
United States of America
State/province [4] 0 0
District of Columbia
Country [5] 0 0
United States of America
State/province [5] 0 0
Florida
Country [6] 0 0
United States of America
State/province [6] 0 0
Indiana
Country [7] 0 0
United States of America
State/province [7] 0 0
Kentucky
Country [8] 0 0
United States of America
State/province [8] 0 0
Louisiana
Country [9] 0 0
United States of America
State/province [9] 0 0
Massachusetts
Country [10] 0 0
United States of America
State/province [10] 0 0
Missouri
Country [11] 0 0
United States of America
State/province [11] 0 0
New York
Country [12] 0 0
United States of America
State/province [12] 0 0
North Carolina
Country [13] 0 0
United States of America
State/province [13] 0 0
Ohio
Country [14] 0 0
United States of America
State/province [14] 0 0
Oklahoma
Country [15] 0 0
United States of America
State/province [15] 0 0
Oregon
Country [16] 0 0
United States of America
State/province [16] 0 0
Pennsylvania
Country [17] 0 0
United States of America
State/province [17] 0 0
Rhode Island
Country [18] 0 0
United States of America
State/province [18] 0 0
South Carolina
Country [19] 0 0
United States of America
State/province [19] 0 0
Vermont
Country [20] 0 0
Canada
State/province [20] 0 0
British Columbia
Country [21] 0 0
Canada
State/province [21] 0 0
Quebec
Country [22] 0 0
Chile
State/province [22] 0 0
Antofagasta
Country [23] 0 0
Chile
State/province [23] 0 0
Santiago
Country [24] 0 0
Chile
State/province [24] 0 0
Valdivia
Country [25] 0 0
Finland
State/province [25] 0 0
Kuopio
Country [26] 0 0
Finland
State/province [26] 0 0
Oulu
Country [27] 0 0
France
State/province [27] 0 0
Toulouse
Country [28] 0 0
Germany
State/province [28] 0 0
Hannover
Country [29] 0 0
Germany
State/province [29] 0 0
Muenchen
Country [30] 0 0
Germany
State/province [30] 0 0
Regensburg
Country [31] 0 0
Germany
State/province [31] 0 0
Siegen
Country [32] 0 0
Israel
State/province [32] 0 0
Ashkelon
Country [33] 0 0
Israel
State/province [33] 0 0
Petah Tikva
Country [34] 0 0
Israel
State/province [34] 0 0
Tel Hashomer
Country [35] 0 0
Italy
State/province [35] 0 0
Milano
Country [36] 0 0
Japan
State/province [36] 0 0
Fukui
Country [37] 0 0
Japan
State/province [37] 0 0
Fukuoka
Country [38] 0 0
Japan
State/province [38] 0 0
Kochi
Country [39] 0 0
Japan
State/province [39] 0 0
Tokushima
Country [40] 0 0
Poland
State/province [40] 0 0
Lublin
Country [41] 0 0
Poland
State/province [41] 0 0
Poznan
Country [42] 0 0
South Africa
State/province [42] 0 0
Bellville
Country [43] 0 0
Spain
State/province [43] 0 0
Barcelona
Country [44] 0 0
Spain
State/province [44] 0 0
Plasencia
Country [45] 0 0
Sweden
State/province [45] 0 0
Stockholm

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

Ethics approval
Ethics application status

Summary
Brief summary
The primary objective of the original study was to assess the safety of semagacestat in
Alzheimer's disease (AD) patients during 24 months of open-label treatment. Baseline for the
efficacy measures is defined as the baseline for feeder studies LFAN (NCT00594568) and LFBC
(NCT00762411). For all safety analyses (adverse events), baseline for patients will be week 0
of this study (LFBF).

Preliminary results from LFAN and 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. Studies LFAN, LFBC
and 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. Very few participants from LFBC
rolled over into LFBF (N = 9). Due to insufficient sample size, the data for LFBC
participants who rolled into LFBF were not analyzed.
Trial website
https://clinicaltrials.gov/show/NCT01035138
Trial related presentations / publications
Public notes

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