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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01969123




Registration number
NCT01969123
Ethics application status
Date submitted
21/10/2013
Date registered
25/10/2013
Date last updated
3/05/2016

Titles & IDs
Public title
Study of the Safety and Effectiveness of Two Doses of Investigational Study Drug EVP-6124 in Subjects With Alzheimer's Disease
Scientific title
A Randomized, Double-blind, Placebo-controlled, Parallel-Group, 26-Week, Phase 3 Study of 2 Doses of EVP-6124 or Placebo in Subjects With Mild to Moderate Alzheimer's Disease Currently or Previously Receiving an Acetylcholinesterase Inhibitor Medication
Secondary ID [1] 0 0
2013-002618-10
Secondary ID [2] 0 0
EVP-6124-024
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Alzheimer's Disease 0 0
Dementia 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 - Drug: EVP-6124
Treatment: Drugs - Placebo

Experimental: Experimental: EVP-6124, low dose - low dose, Tablet, Once Daily, Day 1 through Day 182

Experimental: Experimental: EVP-6124, high dose - high dose, Tablet, Once Daily, Day 1 through Day 182

Placebo Comparator: EVP-6124 Placebo - Placebo, Tablet, Once Daily, Day 1 through Day 182


Treatment: Drugs: Drug: EVP-6124


Treatment: Drugs: Placebo


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

Outcomes
Primary outcome [1] 0 0
Change from Baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale 13-item (ADAS-Cog-13) to Day 182
Timepoint [1] 0 0
Baseline to Day 182 or Early Termination
Primary outcome [2] 0 0
Change from Baseline in the Clinical Dementia Rating Sum of the Boxes (CDR-SB) to Day 182
Timepoint [2] 0 0
Baseline to Day 182 or Early Termination
Primary outcome [3] 0 0
Safety and tolerability of EVP-6124 or Placebo in Subjects with AD - All adverse experiences spontaneously reported by subject and/or observed by an investigator and repeated clinical evaluation of physical exam, vital signs, 12-lead ECG (electrocardiogram), ambulatory ECG and laboratory tests (hematology/blood chemistry/urinalysis)
Timepoint [3] 0 0
Baseline to Day 182 or ET
Secondary outcome [1] 0 0
Change from Baseline in activities of daily living using the Disability Assessment for Dementia (DAD)
Timepoint [1] 0 0
Baseline to Day 182 or Early Termination
Secondary outcome [2] 0 0
Change from Baseline in psychiatric and behavioral symptoms using the Neuropsychiatric Inventory (NPI)
Timepoint [2] 0 0
Baseline to Day 182 or Early Termination
Secondary outcome [3] 0 0
Change from Baseline in the Mini-Mental State Examination (MMSE)
Timepoint [3] 0 0
Baseline to Day 182 or Early Termination
Secondary outcome [4] 0 0
Change from Baseline in the Controlled Oral Word Association Test (COWAT)
Timepoint [4] 0 0
Baseline to Day 182 or Early Termination

Eligibility
Key inclusion criteria
- Ages =55 and =85 years

- Informed consent form (ICF) signed by the subject or legally acceptable representative
before any study-specific procedures for the subject are performed and an ICF signed
by the support person/caregiver before any study-specific procedures for the support
person/caregiver are performed

- Clinical diagnosis of dementia due to probable AD consistent with criteria established
by a workgroup of the National Institute on Aging and the Alzheimer's Disease
Association

- Clinical decline within 12 months before screening and onset of symptoms at least 12
months or longer before screening, which may include any documented cognition,
functional, or other objective assessment or the clinical judgment of the investigator
or the subject's referring physician that the subject has experienced a clinical
decline within the last 12 months

- Magnetic resonance imaging (MRI) or computed tomography (CT) scan performed within 12
months before screening, with findings consistent with the diagnosis of dementia due
to AD without any other clinically significant comorbid pathologies. If an MRI or CT
scan is unavailable or occurred greater than 12 months before screening, this
assessment should be completed and the findings confirmed before the subject enters
the run-in period (Day -14) (copy of the report will be available at the study site)

- Mini-Mental State Examination (MMSE) score =14 and =24 at screening and confirmed on
Day 1 prior to randomization (fluctuations of ±2 points are acceptable on Day
1/baseline)

- Clinical Dementia Rating Global score (CDR-GS) =1 (at least mild dementia) at
screening and confirmed on Day 1 prior to randomization

- Modified Hachinski Ischemic Scale (mHIS) score =4 at screening

- Fertile, sexually active subjects (men and women) must use an effective method of
contraception during the study. Female subjects and the female partner of male
subjects must be surgically sterile (hysterectomy or bilateral tubal ligation),
postmenopausal for at least 1-year, or willing to practice adequate methods of
contraception if of childbearing potential (defined as consistent use of combined
effective methods of contraception [including at least 1 barrier method])

- Reliable and capable support person/caregiver, who if not living in the same
household, interacts with the subject approximately 4 times per week and will be
available to attend clinic visits in person when possible

- Subject living at home, senior residential setting, or an institutional setting
without the need for continuous (ie, 24-hour) nursing care

- General health status acceptable for participation in a 26-week study

- Fluency (oral and written) in the language in which the standardized tests will be
administered

- Receiving a stable dose of an acetylcholinesterase inhibitor (AChEI) (donepezil,
rivastigmine or galantamine) for at least 3 months (90 days) before screening and with
continuous dosing for at least 6 months OR not presently receiving an AChEI (at least
30 days before screening), but with a history of previous AChEI treatment (subjects
receiving donepezil 23 mg currently or within 3 months before screening are
ineligible)
Minimum age
55 Years
Maximum age
85 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Exposure to an experimental drug, experimental biologic or experimental medical device
within 2 months (60 days) before screening

- Prior participation in an amyloid vaccination clinical study at any time in the past
or completion of a passive amyloid vaccination study within 6 months before screening

- Inability to swallow a tablet

- In the judgment of the investigator, inability of the subject or the support
person/caregiver to complete a 26-week study

- Inability to be =75% compliant with single-blind study drug

- Inability to adequately cooperate or complete the cognitive testing procedures or any
study assessment

- Residence in a skilled nursing facility

- Untreated vitamin B12 or folate deficiency (if treated, must be stably treated for at
least 6 months before screening)

- Clinically significant (in the judgment of the investigator) abnormal serum
electrolytes (sodium, potassium, magnesium) after repeat testing

- Clinically significant untreated hypothyroidism (if treated, thyroid-stimulating
hormone level and thyroid supplementation dose must be stable for at least 6 months
before screening)

- Insufficiently controlled diabetes mellitus (in the judgment of the investigator) or
requiring insulin

- Renal insufficiency (serum creatinine >2.0 mg/dL)

- Malignant tumor within 3 years before screening (except squamous and basal cell
carcinoma or cervical carcinoma in situ or localized prostate cancer)

- Female subjects who are pregnant, nursing, or planning to become pregnant during the
study

- Unstable medical condition that is clinically significant in the judgment of the
investigator

- Alanine transaminase (ALT) or aspartate transaminase (AST) >2.5 times the upper limit
of normal

- History of myocardial infarction or unstable angina within 6 months before screening

- History of more than 1 myocardial infarction within 5 years before screening

- Clinically significant (in the judgment of the investigator) cardiac arrhythmia
(including atrial fibrillation), cardiomyopathy, or cardiac conduction defect
(subjects with a pacemaker are acceptable)

- Symptomatic hypotension or hypertension (supine diastolic blood pressure >95 mmHg) (in
the judgment of the investigator)

- Clinically significant abnormality on screening or baseline electrocardiogram (ECG),
including but not necessarily limited to a confirmed corrected QT interval (QTc) value
=450 msec for males or =470 msec for females. In subjects with a QRS value >120msec,
those with a QTc value <500 msec may be eligible following discussion with the Medical
Monitor.

- Stroke within 18 months before screening, or history of a stroke concomitant with
onset of dementia

- History of brain tumor, subdural hematoma, or other clinically significant (in the
judgment of the investigator) space-occupying lesion on CT or MRI

- Head trauma with clinically significant (in the judgment of the investigator) loss of
consciousness within 12 months before screening or concurrent with the onset of
dementia

- Onset of dementia secondary (in the judgment of the investigator) to cardiac arrest,
surgery with general anesthesia, or resuscitation

- Specific degenerative central nervous system (CNS) disease diagnosis other than AD
(eg, Huntington's disease, Creutzfeld-Jacob disease, Down's syndrome, Fronto-Temporal
Dementia, Parkinson's disease)

- Subjects with no history of prior treatment with an AChEI (donepezil, rivastigmine, or
galantamine)

- Memantine currently or within 30 days before screening

- Antipsychotics; low doses (in the judgment of the investigator, except clozapine) are
allowed only if given for sleep disturbances, agitation and/or aggression, and only if
the subject has received a stable dose for at least 3 months before screening (but not
within 8 hours before any cognitive test)

- Tricyclic antidepressants and monoamine oxidase inhibitors; all other antidepressants
are allowed only if the subject has received a stable dose for at least 3 months
before screening

- Antiepileptic medications if taken for control of seizures

- Chronic intake of opioid-containing analgesics

- Sedating H1 antihistamines

- Nicotine therapy (including the patch), varenicline (Chantix), or similar therapeutic
agent within 30 days before screening

- Clinically significant urine drug screen or serum alcohol test result in the judgment
of the investigator

- History of ischemic colitis or ischemic enterocolitis

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 assessing the outcomes
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,VIC
Recruitment hospital [1] 0 0
- Hornsby
Recruitment hospital [2] 0 0
- Geelong
Recruitment hospital [3] 0 0
- West Heidelberg
Recruitment postcode(s) [1] 0 0
- Hornsby
Recruitment postcode(s) [2] 0 0
- Geelong
Recruitment postcode(s) [3] 0 0
- West Heidelberg
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Georgia
Country [5] 0 0
United States of America
State/province [5] 0 0
Illinois
Country [6] 0 0
United States of America
State/province [6] 0 0
Louisiana
Country [7] 0 0
United States of America
State/province [7] 0 0
Maine
Country [8] 0 0
United States of America
State/province [8] 0 0
Massachusetts
Country [9] 0 0
United States of America
State/province [9] 0 0
Mississippi
Country [10] 0 0
United States of America
State/province [10] 0 0
Missouri
Country [11] 0 0
United States of America
State/province [11] 0 0
New Jersey
Country [12] 0 0
United States of America
State/province [12] 0 0
New York
Country [13] 0 0
United States of America
State/province [13] 0 0
North Carolina
Country [14] 0 0
United States of America
State/province [14] 0 0
Ohio
Country [15] 0 0
United States of America
State/province [15] 0 0
Oregon
Country [16] 0 0
United States of America
State/province [16] 0 0
Pennsylvania
Country [17] 0 0
United States of America
State/province [17] 0 0
Texas
Country [18] 0 0
United States of America
State/province [18] 0 0
Utah
Country [19] 0 0
United States of America
State/province [19] 0 0
Vermont
Country [20] 0 0
United States of America
State/province [20] 0 0
Virginia
Country [21] 0 0
Belgium
State/province [21] 0 0
Brussels
Country [22] 0 0
Belgium
State/province [22] 0 0
Leuven
Country [23] 0 0
Belgium
State/province [23] 0 0
St. Truiden
Country [24] 0 0
Canada
State/province [24] 0 0
British Columbia
Country [25] 0 0
Canada
State/province [25] 0 0
Ontario
Country [26] 0 0
Canada
State/province [26] 0 0
Quebec
Country [27] 0 0
France
State/province [27] 0 0
Nice
Country [28] 0 0
France
State/province [28] 0 0
Paris
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France
State/province [29] 0 0
Rouen
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France
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Toulouse cedex 9
Country [31] 0 0
Germany
State/province [31] 0 0
Achim
Country [32] 0 0
Germany
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Köln
Country [33] 0 0
Germany
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Munchen
Country [34] 0 0
Germany
State/province [34] 0 0
Nurnberg
Country [35] 0 0
Italy
State/province [35] 0 0
Brescia
Country [36] 0 0
Italy
State/province [36] 0 0
Milano
Country [37] 0 0
Korea, Republic of
State/province [37] 0 0
Gyenggi-go
Country [38] 0 0
Korea, Republic of
State/province [38] 0 0
Busan
Country [39] 0 0
Korea, Republic of
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Seoul
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Mexico
State/province [40] 0 0
Jalisco
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Mexico
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Nuevo Leon
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Poland
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Bialystok
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Poland
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Bydgoszcz
Country [44] 0 0
Poland
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Poznan
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Poland
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Warszawa
Country [46] 0 0
South Africa
State/province [46] 0 0
Bellville
Country [47] 0 0
South Africa
State/province [47] 0 0
Johannesburg
Country [48] 0 0
South Africa
State/province [48] 0 0
Pretoria
Country [49] 0 0
South Africa
State/province [49] 0 0
Somerset West
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Spain
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Altcante
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Spain
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Barcelona
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Spain
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Burgos
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Spain
State/province [53] 0 0
Madrid

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
FORUM Pharmaceuticals Inc
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to evaluate the safety and efficacy of 2 fixed doses of EVP-6124
compared to placebo for 26 weeks in subjects with mild to moderate Alzheimer's disease
currently receiving stable treatment or previously treated with an acetylcholinesterase
inhibitor.
Trial website
https://clinicaltrials.gov/show/NCT01969123
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
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/NCT01969123