A Study of Lanabecestat (LY3314814) in Participants With Mild Alzheimer's Disease Dementia

ID: NCT02783573
Status: Recruiting
Phase: Phase 3
Start Date: July 01, 2016
First Submitted: May 24, 2016
Last Updated: February 14, 2018
Results: N/A
Organization: Eli Lilly and Company
Sponsors & Collaborators: Eli Lilly and Company, AstraZeneca
Location: Belgium, Canada, China, Czechia, Denmark, France, Japan, Korea, Republic of, United States
Conditions: Alzheimer's Disease
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.

Study Description

Brief Summary

The main purpose of this study is to evaluate the efficacy of the study drug known as lanabecestat in participants with mild Alzheimer's disease (AD) dementia.

Detailed Description

Condition or disease Intervention/treatment Phase

Alzheimer's Disease

Drug: Lanabecestat
Other Names
LY3314814 AZD3293
Drug: Placebo
Other Names
Phase 3

Tracking Information

First Submitted DateMay 24, 2016
Last Update Posted DateFebruary 14, 2018
Start DateJuly 01, 2016
Anticipated Completion DateMarch 01, 2021
Primary Completion DateSeptember 01, 2019
Results First Submitted DateN/A
Received Results Disposit DateN/A

Current Primary Outcome Measures

  • Change from Baseline in Alzheimer´s Disease Assessment Scale- Cognitive Subscale (ADAS-Cog-13) Score [Time Frame: Baseline, Week 78]

Original Primary Outcome Measures

Not Available

Current Secondary Outcome Measures

  • Change from Baseline in Alzheimer´s Disease Cooperative Study Activities of Daily Living Inventory (ADCS-iADL) Instrumental Items Score [Time Frame: Baseline, Week 78]

  • Change from Baseline in Functional Activities Questionnaire (FAQ) Score [Time Frame: Baseline, Week 78]

  • Change from Baseline on the Integrated Alzheimer's Disease Rating Scale (iADRS) Score [Time Frame: Baseline, Week 78]

  • Change from Baseline in the Clinical Dementia Rating - Sum of Boxes (CDR-SB) Score [Time Frame: Baseline, Week 78]

  • Change in Clinical Dementia Rating (CDR) Global Score [Time Frame: From Loss of 1 Global Stage through Week 78]

  • Change from Baseline in Neuropsychiatric Inventory (NPI) Score [Time Frame: Baseline, Week 78]

  • Change from Baseline on the Mini-Mental State Examination (MMSE) [Time Frame: Baseline, Week 78]

  • Change from Baseline in Concentration of Cerebrospinal fluid (CSF) Biomarker Aβ1-42 [Time Frame: Baseline, Week 78]

  • Change from Baseline in Concentration of CSF Biomarker Aβ1-40 [Time Frame: Baseline, Week 78]

  • Change from Baseline in CSF Biomarker Total Tau [Time Frame: Baseline, Week 78]

  • Change from Baseline in CSF Biomarker Phosphorylated Tau [Time Frame: Baseline, Week 78]

  • Change from Baseline in Brain Amyloid Burden using Florbetapir Amyloid Scan [Time Frame: Baseline, Week 78]

  • Change from Baseline in Regional Cerebral Blood Flow (rCBF) using Florbetapir Perfusion Scan [Time Frame: Baseline, Week 78]

  • Change from Baseline in Whole Brain Volume [Time Frame: Baseline, Week 78]

  • Population Pharmacokinetics (PK): Apparent Oral Clearance of Lanabecestat [Time Frame: Predose Week 4 through Week 71]

  • Population PK: Central Volume of Distribution of Lanabecestat [Time Frame: Predose Week 4 through Week 71]

Original Secondary Outcome Measures

Not Available

Study Design

Brief TitleA Study of Lanabecestat (LY3314814) in Participants With Mild Alzheimer's Disease Dementia
Official TitleA Randomized, Double-Blind, Placebo-Controlled and Delayed-Start Study of LY3314814 in Mild Alzheimer's Disease Dementia
Brief Summary

The main purpose of this study is to evaluate the efficacy of the study drug known as lanabecestat in participants with mild Alzheimer's disease (AD) dementia.

Detailed Description

Study TypeInterventional
Study PhasePhase 3
Estimated Enrollment
1899
Allocation
Randomized
Interventional Model
Parallel Assignment
Masking
Triple
Primary Purpose
Treatment
Conditions
Alzheimer's Disease
Target Follow-Up Duration N/A
Biospecimen:
N/A
Sampling MethodN/A
Study PopulationN/A
Intervention
Drug: Lanabecestat

Administered orally

Other Names
LY3314814
AZD3293
Drug: Placebo

Administered orally

Other Names
Study Groups/Cohorts
Dose 1 of Lanabecestat
Dose 1 of lanabecestat given orally once daily for 156 weeks.

Dose 2 of Lanabecestat
Dose 2 of lanabecestat given orally once daily for 156 weeks.

Placebo (Dose 1 of Lanabecestat)
Placebo given orally once daily for 78 weeks and then dose 1 of lanabecestat given orally once daily until week 156.

Placebo (Dose 2 of Lanabecestat)
Placebo given orally once daily for 78 weeks and then dose 2 of lanabecestat given orally once daily until week 156.

Study Arms
Experimental Dose 1 of Lanabecestat
Dose 1 of lanabecestat given orally once daily for 156 weeks.
Drug : Lanabecestat
Administered orally

Experimental Dose 2 of Lanabecestat
Dose 2 of lanabecestat given orally once daily for 156 weeks.
Drug : Lanabecestat
Administered orally

Experimental Placebo (Dose 1 of Lanabecestat)
Placebo given orally once daily for 78 weeks and then dose 1 of lanabecestat given orally once daily until week 156.
Drug : Lanabecestat
Administered orally

Experimental Placebo (Dose 1 of Lanabecestat)
Placebo given orally once daily for 78 weeks and then dose 1 of lanabecestat given orally once daily until week 156.
Drug : Placebo
Administered orally

Experimental Placebo (Dose 2 of Lanabecestat)
Placebo given orally once daily for 78 weeks and then dose 2 of lanabecestat given orally once daily until week 156.
Drug : Placebo
Administered orally

Experimental Placebo (Dose 2 of Lanabecestat)
Placebo given orally once daily for 78 weeks and then dose 2 of lanabecestat given orally once daily until week 156.
Drug : Lanabecestat
Administered orally

Arm Intervention/Treatment
Experimental Dose 1 of Lanabecestat
Dose 1 of lanabecestat given orally once daily for 156 weeks.
Drug : Lanabecestat
Experimental Dose 2 of Lanabecestat
Dose 2 of lanabecestat given orally once daily for 156 weeks.
Drug : Lanabecestat
Experimental Placebo (Dose 1 of Lanabecestat)
Placebo given orally once daily for 78 weeks and then dose 1 of lanabecestat given orally once daily until week 156.
Drug : Lanabecestat
Experimental Placebo (Dose 1 of Lanabecestat)
Placebo given orally once daily for 78 weeks and then dose 1 of lanabecestat given orally once daily until week 156.
Drug : Placebo
Experimental Placebo (Dose 2 of Lanabecestat)
Placebo given orally once daily for 78 weeks and then dose 2 of lanabecestat given orally once daily until week 156.
Drug : Placebo
Experimental Placebo (Dose 2 of Lanabecestat)
Placebo given orally once daily for 78 weeks and then dose 2 of lanabecestat given orally once daily until week 156.
Drug : Lanabecestat

Recruitment Information

Recruitment Status:Recruiting
Enrollment1899
Completion DateMarch 01, 2021
Eligibility Criteria: Inclusion Criteria:
- Participant must meet the National Institute on Aging (NIA) and the Alzheimer's Association (AA) (NIA-AA) criteria for probable AD dementia.
- MMSE score of 20 to 26 inclusive at screening visit.
- For a diagnosis of mild AD dementia, participant must have a CDR global score of 0.5 or 1, with the memory box score ≥0.5 at screening.
- Evidence of amyloid pathology.
- The participant must have a reliable study partner with whom he/she cohabits or has regular contact.

Exclusion Criteria:
- Significant and/or current neurological disease affecting the central nervous system, other than AD, that may affect cognition or ability to complete the study, including but not limited to, other dementias, repetitive head trauma, serious infection of the brain, Parkinson's disease, epilepsy, or cervicocranial vascular disease.
- Participants with any current primary psychiatric diagnosis other than AD if, in the judgment of the investigator, the psychiatric disorder or symptom is likely to confound interpretation of drug effect, affect cognitive assessment, or affect the participant's ability to complete the study. Participants with history of schizophrenia or other chronic psychosis are excluded.
- Within 1 year before the screening visit or between screening and randomization, any of the following: myocardial infarction; moderate or severe congestive heart failure, New York Heart Association class III or IV; hospitalization for, or symptoms of, unstable angina; syncope due to orthostatic hypotension or unexplained syncope; known significant structural heart disease (such as, significant valvular disease, hypertrophic cardiomyopathy); or hospitalization for arrhythmia.
- Congenital QT prolongation.
- Intermittent second- or third-degree atrioventricular (AV) heart block or AV dissociation or history of ventricular tachycardia.
- A corrected QT (QTcF) interval measurement >470 milliseconds (men and women) at screening (as determined at the investigational site).
- History of malignant cancer within the last 5 years.
- History of vitiligo and/or current evidence of post-inflammatory hypopigmentation.
- Calculated creatinine clearance <30 milliliters per minute (Cockcroft-Gault formula; Cockcroft and Gault 1976) at screening.
- Currently enrolled in any other clinical trial involving an investigational product or any other type of medical research judged not to be scientifically or medically compatible with this study.
GenderAll
Age55 Years to 85 Years
Accepts Healthy VolunteersNo
Contacts
Listed Location Countries
Belgium
Canada
China
Czechia
Denmark
France
Germany
Italy
Japan
Korea, Republic of
Mexico
Netherlands
Poland
Portugal
Russian Federation
Spain
Taiwan
United Kingdom
United States
Czech Republic

Administrative Information

NCT Number:NCT02783573
Other Study ID Numbers
16024
I8D-MC-AZET
2015-005625-39
Has Data Monitoring CommitteeYes
U.S. FDA-regulated Product Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Device Product Not Approved or Cleared by U.S. FDA: No
IPD Sharing Statement
Not Available
Responsible Party,
Study Sponsor
Eli Lilly and Company
Collaborators
AstraZeneca
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