Study of the Safety of Two Doses of Investigational Study Drug EVP-6124 in Subjects With Alzheimer's Disease Currently Receiving Memantine
Primary Purpose
Alzheimer's Disease, Dementia, Cognition
Status
Withdrawn
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
EVP-6124
Sponsored by
About this trial
This is an interventional treatment trial for Alzheimer's Disease focused on measuring Alzheimer's disease, Cognition, Alpha-7 nAChR
Eligibility Criteria
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 possible or probable AD consistent with criteria established by a workgroup of the National Institute on Aging and the Alzheimer's Disease Association
- 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 ≥12 and ≤26 at screening
- 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 regularly and will help facilitate clinic visits of the study subject
- 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 24-week study
- Fluency (oral and written) in the language in which the standardized tests will be administered
- Receiving a stable dose of memantine for at least 3 months (90 days) before screening and with continuous dosing for at least 3 months. Additional co-medication with an AChEI (donepezil in any dose form other than 23 mg once daily (QD), rivastigmine or galantamine) is allowed if stable for at least 3 months (90 days) before screening with total continuous exposure for at least 3 months.
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 to complete a 24-week study
- Residence in a skilled nursing facility
- Inability to be ≥75% compliant with single-blind study drug
- 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)
- History of ischemic colitis or ischemic enterocolitis
- Unstable medical condition that is clinically significant in the judgment of the investigator
- Female subjects who are pregnant, nursing, or planning to become pregnant during the study
- 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 uncontrolled hypertension (in the judgment of the investigator)
- Clinically significant abnormality on screening electrocardiogram (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.
- 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 CNS disease diagnosis other than AD (eg, Huntington's disease, Creutzfeld-Jacob disease, Down's syndrome, Fronto-Temporal Dementia, Parkinson's disease)
- Wernicke's encephalopathy
- Active acute or chronic CNS infection
- Donepezil 23 mg QD currently or within 3 months prior to randomization
- Discontinued AChEI <30 days prior to randomization
- 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 randomization
- 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 randomization
- Anxiolytics or sedative-hypnotics, including barbiturates (unless given in low doses for benign tremor); low doses of benzodiazepines and zolpidem (in the judgment of the investigator) are allowed only if given for insomnia/sleep disturbance, and only if the subject has received a stable dose for at least 3 months before randomization
- Peripherally acting drugs with effects on cholinergic transmission
- Immunosuppressants, including systemic corticosteroids, if taken in clinically immunosuppressive doses in the judgment of the investigator (Note: steroid use for allergy or other inflammation is permitted)
- Antiepileptic medications if taken for control of seizures
- Chronic intake of opioid-containing analgesics
- Sedating H1 antihistamines
- Nicotine therapy (all dosage forms including a patch), varenicline (Chantix), or similar therapeutic agent within 30 days before screening
- Clinically significant urine drug screen (UDS) or serum alcohol test result in the judgment of the investigator (including medical marijuana)
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Placebo Comparator
Arm Label
EVP-6124, low dose
EVP-6124, high dose
EVP-6124, Placebo
Arm Description
Low dose, Tablet, Once Daily, Day 1 through Day 168
High dose, Tablet, Once Daily, Day 1 through Day 168
Placebo, Tablet, Once Daily, Day 1 through Day 168
Outcomes
Primary Outcome Measures
Safety/Tolerability of EVP-6124 with concurrent memantine
Number of subjects with AEs
Percentage of subjects with AEs
Number of subjects with SAEs
Percentage of subjects with SAEs
Number of subjects who discontinue due to AEs
Percentage of subjects who discontinue due to AEs
Number of subject deaths
Percentage of subject deaths
Secondary Outcome Measures
Change from Baseline in the Mini-Mental State Examination (MMSE)
Full Information
NCT ID
NCT02246075
First Posted
September 17, 2014
Last Updated
October 13, 2015
Sponsor
FORUM Pharmaceuticals Inc
Collaborators
Quintiles, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT02246075
Brief Title
Study of the Safety of Two Doses of Investigational Study Drug EVP-6124 in Subjects With Alzheimer's Disease Currently Receiving Memantine
Official Title
A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, 24-Week, Phase 2 Study of Two Doses of EVP-6124 Hydrochloride or Placebo in Subjects With Mild to Moderate Alzheimer's Disease Currently Receiving Memantine Medication With or Without Additional Acetylcholinesterase Inhibitor Co-Medication
Study Type
Interventional
2. Study Status
Record Verification Date
October 2015
Overall Recruitment Status
Withdrawn
Why Stopped
Forum has decided not to proceed with this study at this time.
Study Start Date
July 2015 (undefined)
Primary Completion Date
October 2016 (Anticipated)
Study Completion Date
undefined (undefined)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
FORUM Pharmaceuticals Inc
Collaborators
Quintiles, Inc.
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to evaluate the safety of 2 fixed doses of EVP-6124 hydrochloride (HCl) compared to placebo for 24 weeks in subjects with mild to moderate Alzheimer's disease who are concurrently receiving stable treatment with memantine and currently receiving stable treatment or previously treated with an acetylcholinesterase inhibitor.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alzheimer's Disease, Dementia, Cognition
Keywords
Alzheimer's disease, Cognition, Alpha-7 nAChR
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
EVP-6124, low dose
Arm Type
Experimental
Arm Description
Low dose, Tablet, Once Daily, Day 1 through Day 168
Arm Title
EVP-6124, high dose
Arm Type
Experimental
Arm Description
High dose, Tablet, Once Daily, Day 1 through Day 168
Arm Title
EVP-6124, Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo, Tablet, Once Daily, Day 1 through Day 168
Intervention Type
Drug
Intervention Name(s)
EVP-6124
Other Intervention Name(s)
encenicline
Primary Outcome Measure Information:
Title
Safety/Tolerability of EVP-6124 with concurrent memantine
Description
Number of subjects with AEs
Percentage of subjects with AEs
Number of subjects with SAEs
Percentage of subjects with SAEs
Number of subjects who discontinue due to AEs
Percentage of subjects who discontinue due to AEs
Number of subject deaths
Percentage of subject deaths
Time Frame
Baseline to Day 168
Secondary Outcome Measure Information:
Title
Change from Baseline in the Mini-Mental State Examination (MMSE)
Time Frame
Baseline to Day 168
10. Eligibility
Sex
All
Minimum Age & Unit of Time
55 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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 possible or probable AD consistent with criteria established by a workgroup of the National Institute on Aging and the Alzheimer's Disease Association
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 ≥12 and ≤26 at screening
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 regularly and will help facilitate clinic visits of the study subject
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 24-week study
Fluency (oral and written) in the language in which the standardized tests will be administered
Receiving a stable dose of memantine for at least 3 months (90 days) before screening and with continuous dosing for at least 3 months. Additional co-medication with an AChEI (donepezil in any dose form other than 23 mg once daily (QD), rivastigmine or galantamine) is allowed if stable for at least 3 months (90 days) before screening with total continuous exposure for at least 3 months.
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 to complete a 24-week study
Residence in a skilled nursing facility
Inability to be ≥75% compliant with single-blind study drug
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)
History of ischemic colitis or ischemic enterocolitis
Unstable medical condition that is clinically significant in the judgment of the investigator
Female subjects who are pregnant, nursing, or planning to become pregnant during the study
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 uncontrolled hypertension (in the judgment of the investigator)
Clinically significant abnormality on screening electrocardiogram (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.
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 CNS disease diagnosis other than AD (eg, Huntington's disease, Creutzfeld-Jacob disease, Down's syndrome, Fronto-Temporal Dementia, Parkinson's disease)
Wernicke's encephalopathy
Active acute or chronic CNS infection
Donepezil 23 mg QD currently or within 3 months prior to randomization
Discontinued AChEI <30 days prior to randomization
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 randomization
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 randomization
Anxiolytics or sedative-hypnotics, including barbiturates (unless given in low doses for benign tremor); low doses of benzodiazepines and zolpidem (in the judgment of the investigator) are allowed only if given for insomnia/sleep disturbance, and only if the subject has received a stable dose for at least 3 months before randomization
Peripherally acting drugs with effects on cholinergic transmission
Immunosuppressants, including systemic corticosteroids, if taken in clinically immunosuppressive doses in the judgment of the investigator (Note: steroid use for allergy or other inflammation is permitted)
Antiepileptic medications if taken for control of seizures
Chronic intake of opioid-containing analgesics
Sedating H1 antihistamines
Nicotine therapy (all dosage forms including a patch), varenicline (Chantix), or similar therapeutic agent within 30 days before screening
Clinically significant urine drug screen (UDS) or serum alcohol test result in the judgment of the investigator (including medical marijuana)
Facility Information:
City
Delray Beach
State/Province
Florida
Country
United States
City
Albuquerque
State/Province
New Mexico
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Study of the Safety of Two Doses of Investigational Study Drug EVP-6124 in Subjects With Alzheimer's Disease Currently Receiving Memantine
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