Clinical Trials Register

Summary
EudraCT Number:	2015-005625-39
Sponsor's Protocol Code Number:	I8D-MC-AZET
National Competent Authority:	Netherlands - Competent Authority
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2017-02-08
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Netherlands - Competent Authority

A.2

EudraCT number

2015-005625-39

A.3

Full title of the trial

A Randomized, Double-Blind, Placebo-Controlled and Delayed-Start Study of LY3314814 in Mild Alzheimer’s Disease Dementia (The DAYBREAK Study)

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

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

A.3.2

Name or abbreviated title of the trial where available

Daybreak Study

A.4.1

Sponsor's protocol code number

I8D-MC-AZET

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Eli Lilly and Company
B.1.3.4	Country	United States
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Eli Lilly and Company
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Eli Lilly
B.5.2	Functional name of contact point	Clinical Trial Registry Office
B.5.3	Address:
B.5.3.1	Street Address	Lilly Corporate Center, DC 1526
B.5.3.2	Town/ city	Indianapolis
B.5.3.3	Post code	46285
B.5.3.4	Country	United States
B.5.6	E-mail	EU_Lilly_clinical_Trials@Lilly.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	LY3314814 20 mg film-coated tablets
D.3.2	Product code	LY3314814
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Not yet available
D.3.9.1	CAS number	1522418-41-2
D.3.9.2	Current sponsor code	LY3314814
D.3.9.3	Other descriptive name	LY3314814
D.3.9.4	EV Substance Code	SUB181816
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	20
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	LY3314814 50 mg film-coated tablets
D.3.2	Product code	LY3314814
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Not yet available
D.3.9.1	CAS number	1522418-41-2
D.3.9.2	Current sponsor code	LY3314814
D.3.9.3	Other descriptive name	LY3314814
D.3.9.4	EV Substance Code	SUB181816
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	50
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Film-coated tablet
D.8.4	Route of administration of the placebo	Oral use
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Film-coated tablet
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Alzheimer’s Disease with Dementia

E.1.1.1

Medical condition in easily understood language

Medical condition in which an individual's memory, judgment, cognition and eventually ability to function is destroyed.

E.1.1.2

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	PT
E.1.2	Classification code	10012271
E.1.2	Term	Dementia Alzheimer's type
E.1.2	System Organ Class	10029205 - Nervous system disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

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

E.2.2

Secondary objectives of the trial

To evaluate the efficacy of LY3314814 on functional, clinical, and cognitive outcomes in patients with mild AD dementia at the end of the Placebo-Controlled period (week 78).
To evaluate the relationship between treatment effect of LY3314814 and time.
To test the hypothesis that LY3314814 will slow the rate of cognitive and functional decline associated with AD, compared with placebo
To evaluate the efficacy of LY3314814 to prolong time in the current disease state
To evaluate the effect of LY3314814 on CSF Aβ PD markers, CSF markers of neurodegeneration, brain amyloid burden, regional cerebral blood flow, brain aggregated tau levels, brain Metabolism and brain Atrophy

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

1. Protocol Addendum I8D-MC-AZET (1) v 5-Feb-16, The objective of the FDG PET Biomarker addendum: To evaluate the effect of LY3314814 (change from baseline) on brain glucose metabolic rates using FDG PET
2. Protocol Addendum I8D-MC-AZET (2) 18F-AV-1451 Tau Imaging Biomarker v5-Feb-16: The objective of the 18F-AV-1451 Tau Imaging Biomarker addendum:To evaluate change from baseline in brain tau density and distribution as measured by 18F-AV-1451 Tau PET.

E.3

Principal 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.

E.4

Principal 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.

E.5 End points

E.5.1

Primary end point(s)

Change from Baseline in Alzheimer´s Disease Assessment Scale- Cognitive Subscale (ADAS-Cog-13) Score

E.5.1.1

Timepoint(s) of evaluation of this end point

78 weeks from baseline

E.5.2

Secondary end point(s)

• 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

E.5.2.1

Timepoint(s) of evaluation of this end point

Timeframe for most endpoints is 78 weeks from baseline
Exception is Population (PK) - Pre-dose week 4 through week 71

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

Yes

E.6.9

Dose response

Yes

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

Delayed-Start

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Canada

China

Czech Republic

Denmark

France

Germany

Italy

Japan

Korea, Republic of

Mexico

Netherlands

Poland

Portugal

Russian Federation

Spain

Taiwan

United Kingdom

United States

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

Efficacy Study

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

570

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

3230

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

630

F.4.2.2

In the whole clinical trial

3800

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

As defined in the protocol

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2016-06-13

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-11-23

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2018-09-28

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