Study of the Safety and Effectiveness of Two Doses of Investigational Study Drug EVP-6124 in Subjects With Alzheimer's Disease

Sponsor

FORUM Pharmaceuticals Inc (Industry)

Overall Status

Terminated

CT.gov ID

NCT01969136

Collaborator

(none)

403

Enrollment

Locations

Arms

Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Alzheimer's Disease Dementia	Drug: Drug: EVP-6124 Drug: Placebo	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

403 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official 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

Study Start Date :

Oct 1, 2013

Anticipated Primary Completion Date :

Jan 1, 2017

Anticipated Study Completion Date :

Jan 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Experimental: EVP-6124, low dose low dose, Tablet, Once Daily, Day 1 through Day 182	Drug: Drug: EVP-6124
Experimental: Experimental: EVP-6124, high dose high dose, Tablet, Once Daily, Day 1 through Day 182	Drug: Drug: EVP-6124
Placebo Comparator: EVP-6124, Placebo Placebo, Tablet, Once Daily, Day 1 through Day 182	Drug: Placebo

Arm

Intervention/Treatment

Experimental: Experimental: EVP-6124, low dose

low dose, Tablet, Once Daily, Day 1 through Day 182

Drug: Drug: EVP-6124

Experimental: Experimental: EVP-6124, high dose

high dose, Tablet, Once Daily, Day 1 through Day 182

Drug: Drug: EVP-6124

Placebo Comparator: EVP-6124, Placebo

Placebo, Tablet, Once Daily, Day 1 through Day 182

Drug: Placebo

Outcome Measures

Primary Outcome Measures

Change from Baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale 13-item (ADAS-Cog-13) to Day 182 [Baseline to Day 182 or Early Termination]
Change from Baseline in the Clinical Dementia Rating Sum of the Boxes (CDR-SB) to Day 182 [Baseline to Day 182 or Early Termination]
Safety and tolerability of EVP-6124 or Placebo in Subjects with AD [Baseline to Day 182 or ET]
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)

Secondary Outcome Measures

Change from Baseline in activities of daily living using the Disability Assessment for Dementia (DAD) [Baseline to Day 182 or Early Termination]
Change from Baseline in psychiatric and behavioral symptoms using the Neuropsychiatric Inventory (NPI) [Baseline to Day 182 or Early Termination]
Change from Baseline in the Mini-Mental State Examination (MMSE) [Baseline to Day 182 or Early Termination]
Change from Baseline in the Controlled Oral Word Association Test (COWAT) [Baseline to Day 182 or Early Termination]

Eligibility Criteria

Criteria

Ages Eligible for Study:

55 Years to 85 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)

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

Contacts and Locations

Locations

	City	State	Country
1	Tucson	Arizona	United States
2	Little Rock	Arkansas	United States
3	Culver City	California	United States
4	Downey	California	United States
5	Los Alamitos	California	United States
6	Los Angeles	California	United States
7	Oceanside	California	United States
8	Orange	California	United States
9	Norwich	Connecticut	United States
10	Bradenton	Florida	United States
11	Gainesville	Florida	United States
12	Hallandale Beach	Florida	United States
13	Hialeah	Florida	United States
14	Jacksonville	Florida	United States
15	Leesburg	Florida	United States
16	Miami	Florida	United States
17	Sarasota	Florida	United States
18	Sunrise	Florida	United States
19	West Palm Beach	Florida	United States
20	Atlanta	Georgia	United States
21	Elk Grove Village	Illinois	United States
22	Springfield	Illinois	United States
23	Newton	Massachusetts	United States
24	Hattiesburg	Mississippi	United States
25	Albuquerque	New Mexico	United States
26	Albany	New York	United States
27	Cedarhurst	New York	United States
28	New Hyde Park	New York	United States
29	New York	New York	United States
30	Staten Island	New York	United States
31	Charlotte	North Carolina	United States
32	Durham	North Carolina	United States
33	Shaker Heights	Ohio	United States
34	Oklahoma City	Oklahoma	United States
35	Abington	Pennsylvania	United States
36	Jenkintown	Pennsylvania	United States
37	Plains	Pennsylvania	United States
38	East Providence	Rhode Island	United States
39	Houston	Texas	United States
40	Salt Lake City	Utah	United States
41	Charlottesville	Virginia	United States
42	Richland	Washington	United States
43	Rosario	Santa Fe	Argentina
44	Buenos Aires		Argentina
45	Santa Fe		Argentina
46	Box Hill	Victoria	Australia
47	Caulfield South	Victoria	Australia
48	Halifax	Nova Scotia	Canada
49	London	Ontario	Canada
50	Quebec		Canada
51	Brno		Czech Republic
52	Chocen		Czech Republic
53	Hradec Kralove		Czech Republic
54	Praha 6		Czech Republic
55	Richnov nad Kneznou		Czech Republic
56	Bordeaux		France
57	Caen		France
58	Paris		France
59	Homburg		Germany
60	Mittweida		Germany
61	Munchen		Germany
62	Westerstede		Germany
63	Ancona		Italy
64	Milano		Italy
65	Incheon		Korea, Republic of
66	Seoul		Korea, Republic of
67	Saltillo	Coahuila	Mexico
68	Amsterdam		Netherlands
69	Den Haag		Netherlands
70	S'Hertogenbosch		Netherlands
71	Durban	Kwa-Zulu Natal	South Africa
72	Bellville	Western Cape	South Africa
73	George	Western Cape	South Africa
74	Madrid		Spain
75	Salamanca		Spain
76	West End	Southampton	United Kingdom
77	Bath		United Kingdom
78	Glasgow		United Kingdom
79	Isleworth		United Kingdom
80	Northampton		United Kingdom
81	Penarth		United Kingdom

Sponsors and Collaborators

FORUM Pharmaceuticals Inc

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

FORUM Pharmaceuticals Inc

ClinicalTrials.gov Identifier:

NCT01969136

Other Study ID Numbers:

EVP-6124-025
2013-002653-30

First Posted:

Oct 25, 2013

Last Update Posted:

May 3, 2016

Last Verified:

Sep 1, 2015

Keywords provided by FORUM Pharmaceuticals Inc

Alzheimer's disease

Cognition

Alpha-7 nAChR

Additional relevant MeSH terms:

Alzheimer Disease

Study Results

No Results Posted as of May 3, 2016