Mild to moderate Alzheimer's disease MedDRA version: 17.0 Level: LLT Classification code 10001896 Term: Alzheimer's disease System Organ Class: 10029205 - Nervous system disorders MedDRA version: 17.0 Level: SOC Classification code 10029205 Term: Nervous system disorders System Organ Class: 10029205 - Nervous system disorders
Conditions
Interventions
Product Name: EVP-6124
Product Code: EVP-6124
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: EVP-6124
CAS Number: 1350343-
Sponsors
Forum Pharmaceuticals Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects must meet all of the following inclusion criteria to be eligible to participate in the study: 1. 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. 2. Male or female subjects of any race, aged =55 and =85 years 3. 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 (McKhann et al, 2011) 4. 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 5. 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) 6. 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) 7. Clinical Dementia Rating Global score (CDR-GS) =1 (at least mild dementia) at screening and confirmed on Day 1 prior to randomization 8. Modified Hachinski Ischemic Scale (mHIS) score =4 at screening 9. 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. 10. 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. 11. Subject living at home, senior residential setting, or an institutional setting without the need for continuous (ie, 24-hour) nursing care. 12. General health status acceptable for participation in a 26-week study 13. Fluency (oral and written) in the language in which the standardized tests will be administered 14. Receiving a stable dose of an 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 w
Exclusion criteria
Exclusion criteria: Subjects who meet any of the following exclusion criteria will be excluded from participating in the study: General 1. Exposure to an experimental drug, experimental biologic or experimental medical device within 2 months (60 days) before screening 2. 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 3. Inability to swallow a tablet 4. In the judgment of the investigator, inability of the subject or the support person/caregiver to complete a 26-week study 5. Inability to be =75% compliant with single-blind study drug 6. Inability to adequately cooperate or complete the cognitive testing procedures or any study assessment 7. Residence in a skilled nursing facility Medical 8. Untreated vitamin B12 or folate deficiency (if treated, must be stably treated for at least 6 months before screening) 9. Clinically significant (in the judgment of the investigator) abnormal serum electrolytes (sodium, potassium, magnesium) after repeat testing 10. Clinically significant untreated hypothyroidism (if treated, thyroid-stimulating hormone level and thyroid supplementation dose must be stable for at least 6 months before screening) 11. Insufficiently controlled diabetes mellitus (in the judgment of the investigator) or requiring insulin 12. Renal insufficiency (serum creatinine >2.0 mg/dL) 13. Malignant tumor within 3 years before screening (except squamous and basal cell carcinoma or cervical carcinoma in situ or brachytherapy for localized prostate cancer) 14. Unstable medical condition that is clinically significant in the judgment of the investigator 15. Female subjects who are pregnant, nursing, or planning to become pregnant during the study 16. Alanine transaminase (ALT) or aspartate transaminase (AST) >2.5 times the upper limit of normal Cardiovascular 17. History of myocardial infarction or unstable angina within 6 months before screening 18. History of more than 1 myocardial infarction within 5 years before screening 19. Clinically significant (in judgment of the investigator) cardiac arrhythmia (including atrial fibrillation), cardiomyopathy, or cardiac conduction defect (subjects with a pacemaker are acceptable) 20. Symptomatic hypotension or hypertension (supine diastolic blood pressure >95 mmHg) (in the judgment of the investigator) 21. Clinically significant abnormality on screening or baseline ECG, including but not necessarily limited to a confirmed 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. Psychiatric 22. Diagnosis of severe major depressive disorder with psychotic features, delusions or hallucinations, which is either recurrent (Diagnostic and Statistical Manual of Mental Disorders 4th Edition Text Revision [DSM-IV-TR] 296.34) or single episode (DSM-IV-TR 296.24) within 5 years
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): The co-primary efficacy endpoints for this study include the mean change from baseline to Day 182 in the cognitive (Alzheimer’s Disease Assessment Scale-Cognitive Subscale 13-item [ADAS-Cog-13]) and functional/global (Disability Assessment for Dementia [DAD]) endpoints. ;Main Objective: The primary objectives are to evaluate the safety and efficacy of 2 fixed doses of EVP-6124 (2 or 3 mg daily) compared to placebo for 26 weeks in subjects with mild to moderate dementia due to AD currently receiving stable treatment or previously treated with an AChEI (donepezil, rivastigmine, or galantamine). The primary efficacy response will be an assessment of the change from baseline in cognitive, (ADAS-Cog-13) and functional/global (Disability Assessment for Dementia [DAD]) endpoints. ; Secondary Objective: The secondary objectives are to assess the effects of EVP-6124 compared with placebo on the following endpoints for 26 weeks: • Change in activities of daily living using the Disability Assessment for Dementia (DAD) • Change in psychiatric and behavioral symptoms using the Neuropsychiatric Inventory (NPI) • Additional assessments of cognition include the Mini-Mental State Examination (MMSE) and the Controlled Oral Word Association Test (COWAT) ; Timepoint(s) of evaluation of this end point: ADAS-Cog-13: Day -14 (run-in), baseline (predose on Day 1) and Days 84, 140, and 182 or early termination. DAD: Day 1 (predose), and days 84, 140, and 182 or early termination. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): ADAS-Cog-11 (derived from the ADAS-Cog-13), Alzheimer’s Disease Assessment Scale, Cognitive Subscale-11, MMSE (Mini-Mental State Examination) COWAT (Controlled Oral Word Association Test), DAD (Disability Assessment for Dementia:), NPI (Neuropsychiatric Inventory) ; Timepoint(s) of evaluation of this end point: ADAS-Cog-11 (derived from the ADAS-Cog-13): Day -14 (run-in), baseline (predose on Day 1) and Days 84, 140, and 182 or early termination. MMSE (Mini-Mental State Examination): Pre-Run-in and Days 1 (predose), 28, 84, and 182 or early termination. COWAT (Controlled Oral Word Association Test): (Day -14) Run-in and Day 1 (predose), and days 84 and 182 or early termination DAD (Disability Assessment for Dementia): Day 1 (predose), and days 84, 140, and 182 or early termination. NPI (Neuropsychiatric Inventory): Days 1 (predose), 84, and 182 or early termination. | — |
Countries
Argentina, Australia, Canada, Czech Republic, France, Germany, Italy, Japan, Korea, Republic of, Mexico, Netherlands, Portugal, South Africa, Spain, United Kingdom, United States
Contacts
Public ContactClinical Trials
inVentiv Health Clinical UK Ltd
Outcome results
None listed