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: NCT01969123
• Collaborator: (none)
• Enrollment: 474
• Locations: 82
• Arms: 3
• Duration (Months): 39
• Patients Per Site: 5.8
• Patients Per Site Per Month: 0.1

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: 474 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

Outcome Measures

Primary Outcome Measures

1. 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]

2. Change from Baseline in the Clinical Dementia Rating Sum of the Boxes (CDR-SB) to Day 182 [Baseline to Day 182 or Early Termination]

3. 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

1. Change from Baseline in activities of daily living using the Disability Assessment for Dementia (DAD) [Baseline to Day 182 or Early Termination]

2. Change from Baseline in psychiatric and behavioral symptoms using the Neuropsychiatric Inventory (NPI) [Baseline to Day 182 or Early Termination]

3. Change from Baseline in the Mini-Mental State Examination (MMSE) [Baseline to Day 182 or Early Termination]

4. 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: No

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

	Site	City	State	Country	Postal Code
1		Phoenix	Arizona	United States
2		Tucson	Arizona	United States
3		Costa Mesa	California	United States
4		Encino	California	United States
5		Glendale	California	United States
6		Long Beach	California	United States
7		Redding	California	United States
8		San Diego	California	United States
9		Atlantis	Florida	United States
10		Brooksville	Florida	United States
11		Delray Beach	Florida	United States
12		Fort Myers	Florida	United States
13		Lake Worth	Florida	United States
14		Miami	Florida	United States
15		Orlando	Florida	United States
16		St. Petersburg	Florida	United States
17		Weston	Florida	United States
18		Columbus	Georgia	United States
19		Douglasville	Georgia	United States
20		Chicago	Illinois	United States
21		Park Ridge	Illinois	United States
22		Baton Rouge	Louisiana	United States
23		Bangor	Maine	United States
24		Chestnut Hill	Massachusetts	United States
25		Plymouth	Massachusetts	United States
26		Flowood	Mississippi	United States
27		Creve Coeur	Missouri	United States
28		Princeton	New Jersey	United States
29		Springfield	New Jersey	United States
30		Brooklyn	New York	United States
31		Latham	New York	United States
32		New York	New York	United States
33		Staten Island	New York	United States
34		Wilmington	North Carolina	United States
35		Columbus	Ohio	United States
36		Portland	Oregon	United States
37		Norristown	Pennsylvania	United States
38		Philadelphia	Pennsylvania	United States
39		San Antonio	Texas	United States
40		Wichita Falls	Texas	United States
41		Murray	Utah	United States
42		Salt Lake City	Utah	United States
43		Bennington	Vermont	United States
44		Williamsburg	Virginia	United States
45		Hornsby	New South Wales	Australia
46		Geelong	Victoria	Australia
47		West Heidelberg	Victoria	Australia
48		Brussels		Belgium
49		Leuven		Belgium
50		St. Truiden		Belgium
51		Kelowna	British Columbia	Canada
52		Chatham	Ontario	Canada
53		Toronto	Ontario	Canada
54		Gatineau	Quebec	Canada
55		Nice		France
56		Paris		France
57		Rouen		France
58		Toulouse cedex 9		France
59		Achim		Germany
60		Köln		Germany
61		Munchen		Germany
62		Nurnberg		Germany
63		Brescia		Italy
64		Milano		Italy
65		Seongnam-si	Gyenggi-go	Korea, Republic of
66		Busan		Korea, Republic of
67		Seoul		Korea, Republic of
68		Guadalajara	Jalisco	Mexico
69		Monterrey	Nuevo Leon	Mexico
70		Bialystok		Poland
71		Bydgoszcz		Poland
72		Poznan		Poland
73		Warszawa		Poland
74		Bellville		South Africa
75		Johannesburg		South Africa
76		Pretoria		South Africa
77		Somerset West		South Africa
78		Elche	Altcante	Spain
79		Terrassa	Barcelona	Spain
80		Barcelona		Spain
81		Burgos		Spain
82		Madrid		Spain

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: NCT01969123
• Other Study ID Numbers: EVP-6124-024; 2013-002618-10
• 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