Trial Review

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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/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
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
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
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
Sex
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
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/10/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/01/2017
Actual
Sample size
Target
Accrual to date
Final
474
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
Country [29] 0 0
France
State/province [29] 0 0
Rouen
Country [30] 0 0
France
State/province [30] 0 0
Toulouse cedex 9
Country [31] 0 0
Germany
State/province [31] 0 0
Achim
Country [32] 0 0
Germany
State/province [32] 0 0
Köln
Country [33] 0 0
Germany
State/province [33] 0 0
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
State/province [39] 0 0
Seoul
Country [40] 0 0
Mexico
State/province [40] 0 0
Jalisco
Country [41] 0 0
Mexico
State/province [41] 0 0
Nuevo Leon
Country [42] 0 0
Poland
State/province [42] 0 0
Bialystok
Country [43] 0 0
Poland
State/province [43] 0 0
Bydgoszcz
Country [44] 0 0
Poland
State/province [44] 0 0
Poznan
Country [45] 0 0
Poland
State/province [45] 0 0
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
Country [50] 0 0
Spain
State/province [50] 0 0
Altcante
Country [51] 0 0
Spain
State/province [51] 0 0
Barcelona
Country [52] 0 0
Spain
State/province [52] 0 0
Burgos
Country [53] 0 0
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
Trial website
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

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results not provided in https://clinicaltrials.gov/study/NCT01969123