To test the hypothesis that LY3314814, administered orally at doses of 20 and 50 mg daily for 78 weeks, will slow the decline of AD ascompared with placebo in patients with mild AD dementia.
ID
Source
Brief title
Condition
- Dementia and amnestic conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Change from Baseline in Alzheimer*s Disease Assessment Scale- Cognitive
Subscale (ADAS-Cog-13) Score
Secondary outcome
• Change from Baseline in Alzheimer*s Disease Cooperative Study Activities of
Daily Living Inventory (ADCS-iADL) Instrumental Items
Score
• Change from Baseline in Functional Activities Questionnaire (FAQ) Score
• Change from Baseline on the Integrated Alzheimer's Disease Rating Scale
(iADRS) Score
• Change from Baseline in the Clinical Dementia Rating - Sum of Boxes (CDR-SB)
Score
• Change in Clinical Dementia Rating (CDR) Global Score
• Change from Baseline in Neuropsychiatric Inventory (NPI) Score
• Change from Baseline on the Mini-Mental State Examination (MMSE)
• Change from Baseline in Concentration of Cerebrospinal fluid (CSF) Biomarker
Aβ1-42
• Change from Baseline in Concentration of CSF Biomarker Aβ1-40
• Change from Baseline in CSF Biomarker Total Tau
• Change from Baseline in CSF Biomarker Phosphorylated Tau
• Change from Baseline in Brain Amyloid Burden using Florbetapir Amyloid Scan
• Change from Baseline in Regional Cerebral Blood Flow (rCBF) using Florbetapir
Perfusion Scan
• Change from Baseline in Whole Brain Volume
• Population Pharmacokinetics (PK): Apparent Oral Clearance of LY3314814
• Population PK: Central Volume of Distribution of LY3314814
Background summary
Alzheimer*s disease is a progressive and fatal neurodegenerative disease
manifested by cognitive deterioration in addition to progressive impairment of
activities of daily living. Current treatments are seen as minimally effective,
with only minor symptomatic improvements for a
limited duration, and they do not slow the progression of the disease.
Study objective
To test the hypothesis that LY3314814, administered orally at doses of 20 and
50 mg daily for 78 weeks, will slow the decline of AD as
compared with placebo in patients with mild AD dementia.
Study design
Study I8D-MC-AZET is a multicenter, randomized, parallel-group, 78-week
double-blind, placebo-controlled, study of 2 fixed doses of LY3314814 in
patients with mild AD dementia and abnormal levels of amyloid, followed by a
78-week Delayed-Start period.
Intervention
There are 4 treatment arms. The randomization ratio is 2:2:1:1 (LY3314814 20
mg: LY3314814 50 mg: Placebo for 78 weeks then LY3314814 20 mg; Placebo for 78
weeks then LY3314814 50 mg). The three treatment groups in the 78-week
Placebo-Controlled period include 2 fixed doses of LY3314814 (20 mg or 50 mg)
or placebo. In the 78-week Delayed-Start period, there are the same 2 fixed
doses of LY3314814 (20 mg or 50 mg) and all patients previously on placebo will
then initiate either dose of LY3314814 based on their randomization.
Study burden and risks
To date, no safety issues have been identified that would create an unfavorable
benefit-risk balance for LY3314814. The potential benefits are not established
but expectation for an effect in slowing AD progression is described above in
the Section 3.2 of the protocol. Potential risks include but are not limited to
elevated liver enzymes, QT-prolongation with overdose, skin or hair
hypopigmentation, rash, retinal changes, and potential interactions with other
drugs. The potential risks are monitored with scheduled labs,
electrocardiograms (ECGs), skin exams, eye
exams, and restrictions on some concomitant medications.
Erl Wood Manor, Sunninghill Road -
Windlesham, Surrey GU20 6PH
GB
Erl Wood Manor, Sunninghill Road -
Windlesham, Surrey GU20 6PH
GB
Listed location countries
Age
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.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2015-005625-39-NL |
| CCMO | NL56998.056.16 |