A Study of Semagacestat for Alzheimer's Patients (Identity XT)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01035138
First received: December 17, 2009
Last updated: September 22, 2014
Last verified: September 2014
  Purpose

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.


Condition Intervention Phase
Alzheimer's Disease
Drug: semagacestat
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official 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)

Resource links provided by NLM:


Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog11) at Week 16 After Cessation of Study Drug [ Time Frame: Baseline (LFAN randomization), 16 weeks (LFBF) after cessation of study drug ] [ Designated as safety issue: Yes ]
    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.

  • Change From Baseline in Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory (ADCS-ADL) at Week 16 After Cessation of Study Drug [ Time Frame: Baseline (LFAN randomization), 16 weeks (LFBF) after cessation of study drug ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • Percent Change From Baseline in Amyloid Beta (Aβ) 1-42 Plasma Concentration at Week 12 [ Time Frame: Baseline (LFAN Randomization ), 6 hours pose-dose at Week 12 (LFBF) ] [ Designated as safety issue: No ]
    Concentration of amino acid peptide known as Aβ 1-42 in plasma. Least Square (LS) Mean value was controlled for baseline value, age, and investigator.

  • Change From Baseline in Hippocampal Volume Using Volumetric Magnetic Resonance Imaging (vMRI) at Week 12 [ Time Frame: Baseline (LFAN Randomization), 12 weeks (LFBF) ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Amyloid Imaging Positron Emission Tomography (AV-45-PET) at Week 12 [ Time Frame: Baseline (LFAN Randomization), 12 weeks (LFBF) ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog11) at Week 12 [ Time Frame: Baseline (LFAN Randomization), 12 weeks (LFBF) ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog12) at Week 12 [ Time Frame: Baseline (LFAN Randomization), 12 weeks (LFBF) ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog14) at Week 12 [ Time Frame: Baseline (LFAN Randomization), 12 weeks (LFBF) ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory (ADCS-ADL) at Week 12 [ Time Frame: Baseline (LFAN Randomization), 12 weeks (LFBF) ] [ Designated as safety issue: No ]
    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.

  • Mean Concentration of LY450139 [ Time Frame: 3 months (pre-dose, 2, 4, and 6 hours after dosing )(LFBF) ] [ Designated as safety issue: No ]
  • Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog12) at Week 16 After Cessation of Study Drug [ Time Frame: Baseline (LFAN Randomization), 16 weeks (LFBF) after cessation of study drug ] [ Designated as safety issue: Yes ]
    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.

  • Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog14) at Week 16 After Cessation of Study Drug [ Time Frame: Baseline (LFAN Randomization), 16 weeks (LFBF) after cessation of study drug ] [ Designated as safety issue: Yes ]
    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.

  • Change From Baseline in Clinical Dementia Rating Scale (Sum of Boxes) (CDR-SB) at Week 24 [ Time Frame: Baseline (LFAN Randomization), 24 weeks (LFBF) ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Mini-Mental State Examination (MMSE) at Week 24 [ Time Frame: Baseline (LFAN Randomization), 24 weeks (LFBF) ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Neuropsychiatric Inventory (NPI) at Week 24 [ Time Frame: Baseline (LFAN Randomization), 24 weeks (LFBF) ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in EuroQol-5D (EQ-5D) at Week 24 [ Time Frame: Baseline (LFAN Randomization), 24 weeks (LFBF) ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Resource Utilization in Dementia-Lite Questionnaire (RUD-Lite) at Week 12 [ Time Frame: Baseline (LFAN Randomization), 12 weeks (LFBF) ] [ Designated as safety issue: No ]
    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.


Enrollment: 180
Study Start Date: December 2009
Study Completion Date: April 2011
Primary Completion Date: April 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Drug: semagacestat Drug: semagacestat
140mg administered orally, once daily for 24 months; dose reduction to 100mg or 60 mg possible due to intolerability
Other Names:
  • semagacestat
  • LY450139

  Eligibility

Ages Eligible for Study:   55 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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

Exclusion Criteria:

  • Meets LFAN or LFBC study discontinuation criteria at the last visit of the LFAN or LFBC study
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01035138

  Show 71 Study Locations
Sponsors 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

No publications provided

Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT01035138     History of Changes
Other Study ID Numbers: 5930, H6L-MC-LFBF
Study First Received: December 17, 2009
Results First Received: November 6, 2013
Last Updated: September 22, 2014
Health Authority: Australia: Department of Health and Ageing Therapeutic Goods Administration
Canada: Health Canada
Chile: Instituto de Salud Pública de Chile
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
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
Sweden: Medical Products Agency
United States: Food and Drug Administration

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 October 19, 2014