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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02972658




Registration number
NCT02972658
Ethics application status
Date submitted
21/11/2016
Date registered
23/11/2016
Date last updated
3/12/2019

Titles & IDs
Public title
A Study of Lanabecestat (LY3314814) in Early Alzheimer's Disease Dementia
Scientific title
A Randomized, Double-Blind, Delayed-Start Study of LY3314814 (AZD3293) in Early Alzheimer's Disease Dementia (Extension of Study AZES, The AMARANTH Study)
Secondary ID [1] 0 0
I8D-MC-AZFD
Secondary ID [2] 0 0
16557
Universal Trial Number (UTN)
Trial acronym
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 - Lanabecestat

Experimental: AZES Lanabecestat 20 milligrams (mg)/AZFD Lanabecestat 20 mg - Participants who received Lanabecestat 20 mg in the feeder study (AZES) were randomized to receive Lanabecestat 20 mg.

Experimental: AZES Lanabecestat 50 mg/AZFD Lanabecestat 50 mg - Participants who received Lanabecestat 50 mg in the feeder study (AZES) were randomized to receive Lanabecestat 50 mg.

Experimental: AZES Placebo/AZFD Lanabecestat 20 mg - Participants who received placebo in the feeder study (AZES) were randomized to receive Lanabecestat 20 mg.

Experimental: AZES Placebo/AZFD Lanabecestat 50 mg - Participants who received placebo in the feeder study (AZES) were randomized to receive Lanabecestat 50 mg.


Treatment: Drugs: Lanabecestat
Administered orally

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change From Baseline Analysis on the 13-item Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog13) - ADAS-Cog13 (13-item version of ADAS-Cog) is a psychometric instrument that evaluates word recall, ability to follow commands, constructional praxis, naming, ideational praxis, orientation, word recognition, memory, comprehension of spoken language, word-finding, and language ability, with a measure of delayed word recall and concentration/ distractibility. The total score of the 13-item scale ranges from 0 to 85, with an increase in score indicating cognitive worsening. Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with factors for treatment, visit, treatment*visit, baseline efficacy score, baseline efficacy score-by-visit interaction, disease status at baseline, apolipoprotein E4 (APOE4) status, acetylcholinesterase inhibitor (AChEI) use at baseline, age at baseline, and pooled country.
Timepoint [1] 0 0
AZES Baseline through AZFD Week 26
Secondary outcome [1] 0 0
Change From Baseline Analysis on the Alzheimer´s Disease Cooperative Study Activities of Daily Living Inventory Instrumental Items (ADCS-iADL) - The ADCS-ADL is a 23-item inventory developed as a rater-administered questionnaire answered by the participant's caregiver. The ADCS-ADL measures both basic and instrumental activities of daily living by participants. The range for the ADCS-iADL is 0-59 with higher scores reflecting better performance. LS Mean was determined by MMRM with factors for treatment, visit, treatment*visit, baseline efficacy score, baseline efficacy score-by-visit interaction, disease status at baseline, APOE4 status, AChEI use at baseline, age at baseline, and pooled country.
Timepoint [1] 0 0
AZES Baseline through AZFD Week 26
Secondary outcome [2] 0 0
Change From Baseline on the Functional Activities Questionnaire (FAQ) Score - FAQ is a 10-item, caregiver-questionnaire and was administered to the study partner and asked to rate the participant's ability to perform a variety of activities ranging from writing checks, assembling tax records, shopping, playing games, food preparation, traveling, keeping appointments, traveling out of neighborhood, keeping track of current events and understanding media. FAQ total score was calculated by adding the scores from each of the 10 items. Each activity is rated on a scale from 0 to 3 (Never did and would have difficulty now =1; Never did but could do now =0; Normal =0; Has difficulty but does by self =1; Requires assistance =2; Dependent =3). FAQ scale is 0 to 30, with higher scores indicating greater impairment. LS Mean was determined by MMRM with factors for treatment, visit, treatment*visit, baseline efficacy score, baseline efficacy score-by-visit interaction, disease status at baseline, APOE4 status, AChEI use at baseline, age at baseline, and pooled country.
Timepoint [2] 0 0
AZES Baseline through AZFD Week 26
Secondary outcome [3] 0 0
Change From Baseline on the Integrated Alzheimer's Disease Rating Scale (iADRS) Score - The iADRS is a composite that measures both cognition and function. The iADRS comprises scores form the ADAS- Cog and the ADCS-iADL. The iADRS is calculated as a linear combination of the total scores of the ADAS-Cog13 (score range 0 to 85 with higher scores reflecting worse performance) and the ADCS-iADL (score range from 0-59 with higher scores reflecting better performance). The iADRS score ranges from 0 to 144 with higher scores indicating greater impairment. LS Mean was determined by MMRM with factors for treatment, visit, treatment*visit, baseline efficacy score, baseline efficacy score-by-visit interaction, disease status at baseline, APOE4 status, AChEI use at baseline, age at baseline, and pooled country.
Timepoint [3] 0 0
AZES Baseline through AZFD Week 26
Secondary outcome [4] 0 0
Change From Baseline on the Mini-Mental Status Examination (MMSE) - The MMSE is an instrument used to assess a participant's cognitive function. The MMSE assesses orientation to time and place, immediate and delayed recall of words, attention and calculation, language (naming, comprehension and repetition), and spatial ability (copying a figure). The range for MMSE total Score is 0 to 30, with a higher score indicating better cognitive performance. LS Mean was determined by MMRM methodology with factors for treatment, visit, treatment*visit, baseline efficacy score, baseline efficacy score-by-visit interaction, disease status at baseline, APOE4 status, AChEI use at baseline, age at baseline, and pooled country.
Timepoint [4] 0 0
AZES Baseline through AZFD Week 26
Secondary outcome [5] 0 0
Change From Baseline Analysis on the ADAS-Cog13 - ADAS-cog13 (13-item ADAS cog) is a psychometric instrument that evaluates word recall, ability to follow commands, constructional praxis, naming, ideational praxis, orientation, word recognition, memory, comprehension of spoken language, word-finding, and language ability, with a measure of delayed word recall and concentration/ distractibility. The total score of the 13-item scale ranges from 0 to 85, with an increase in score indicating cognitive worsening. Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with factors for treatment, visit, treatment*visit, baseline efficacy score, baseline efficacy score-by-visit interaction, disease status at baseline, APOE4 status, AChEI use at baseline, age at baseline, and pooled country.
Timepoint [5] 0 0
AZES Baseline through AZFD Week 52

Eligibility
Key inclusion criteria
- Participants previously enrolled in AMARANTH (NCT02245737) who meet eligibility
criteria for delayed-start I8D-MC-AZFD.
Minimum age
55 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Participants who participate in AMARANTH (NCT02245737) who develop new conditions
precluding them from enrolling into I8D-MC-AZFD.

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 analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
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,SA,VIC,WA
Recruitment hospital [1] 0 0
Southern Neurology - Kogarah
Recruitment hospital [2] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [3] 0 0
Eastern Clinical Research Unit - Box Hill
Recruitment hospital [4] 0 0
Delmont Private Hospital - Glen Iris
Recruitment hospital [5] 0 0
The Florey Institute of Neuroscience and Mental Health - Parkville
Recruitment hospital [6] 0 0
Australian Alzheimer's Research Foundation - Nedlands
Recruitment hospital [7] 0 0
Neuro Trials Victoria Pty Ltd - Noble Park
Recruitment postcode(s) [1] 0 0
2217 - Kogarah
Recruitment postcode(s) [2] 0 0
5000 - Adelaide
Recruitment postcode(s) [3] 0 0
3128 - Box Hill
Recruitment postcode(s) [4] 0 0
3146 - Glen Iris
Recruitment postcode(s) [5] 0 0
3052 - Parkville
Recruitment postcode(s) [6] 0 0
6009 - Nedlands
Recruitment postcode(s) [7] 0 0
3174 - Noble Park
Recruitment outside Australia
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Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
AstraZeneca
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Eli Lilly and Company
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
This study is an extension of study I8D-MC-AZES (NCT02245737), the AMARANTH study. The
purpose of this study is to evaluate the effectiveness of the study drug lanabecestat in
participants with early Alzheimer's disease dementia at the time of entry into study
I8D-MC-AZES.
Trial website
https://clinicaltrials.gov/show/NCT02972658
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

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT02972658