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

NCT01969123 | Terminated Phase 3

• 2 other identifiers: EVP-6124-0242013-002618-10
• Study Type: interventional
• Target: 474
• Locations: 12 countries
• Sites: 82

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.

Conditions

Alzheimer's Disease; Dementia

Keywords

Alzheimer's disease; Cognition; Alpha-7 nAChR

Outcome Measures

Primary Outcomes (3)

• 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

  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)

  Baseline to Day 182 or ET

Secondary Outcomes (4)

• 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

Study Arms (3)

Experimental: EVP-6124, low dose

EXPERIMENTAL

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

Drug: Drug: EVP-6124

Experimental: EVP-6124, high dose

EXPERIMENTAL

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

Drug: Drug: EVP-6124

EVP-6124 Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Drug: EVP-6124 DRUG

Experimental: EVP-6124, high dose; Experimental: EVP-6124, low dose

Placebo DRUG

EVP-6124 Placebo

Eligibility Criteria

• Age: 55 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• FORUM Pharmaceuticals Inc: lead

Study Sites (82)

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Phoenix, Arizona, United States

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Tucson, Arizona, United States

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Costa Mesa, California, United States

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Encino, California, United States

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Glendale, California, United States

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Long Beach, California, United States

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Redding, California, United States

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San Diego, California, United States

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Atlantis, Florida, United States

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Brooksville, Florida, United States

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Delray Beach, Florida, United States

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Fort Myers, Florida, United States

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Lake Worth, Florida, United States

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Miami, Florida, United States

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Orlando, Florida, United States

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St. Petersburg, Florida, United States

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Weston, Florida, United States

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Columbus, Georgia, United States

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Douglasville, Georgia, United States

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Chicago, Illinois, United States

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Park Ridge, Illinois, United States

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Baton Rouge, Louisiana, United States

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Bangor, Maine, United States

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Chestnut Hill, Massachusetts, United States

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Plymouth, Massachusetts, United States

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Flowood, Mississippi, United States

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Creve Coeur, Missouri, United States

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Princeton, New Jersey, United States

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Springfield, New Jersey, United States

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Brooklyn, New York, United States

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Latham, New York, United States

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New York, New York, United States

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Staten Island, New York, United States

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Wilmington, North Carolina, United States

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Columbus, Ohio, United States

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Portland, Oregon, United States

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Norristown, Pennsylvania, United States

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Philadelphia, Pennsylvania, United States

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San Antonio, Texas, United States

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Wichita Falls, Texas, United States

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Murray, Utah, United States

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Salt Lake City, Utah, United States

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Bennington, Vermont, United States

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Williamsburg, Virginia, United States

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Hornsby, New South Wales, Australia

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Geelong, Victoria, Australia

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West Heidelberg, Victoria, Australia

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Brussels, Belgium

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Leuven, Belgium

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Saint Truiden, Belgium

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Kelowna, British Columbia, Canada

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Chatham, Ontario, Canada

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Toronto, Ontario, Canada

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Gatineau, Quebec, Canada

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Nice, France

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Paris, France

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Rouen, France

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Toulouse, France

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Achim, Germany

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Cologne, Germany

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München, Germany

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Nuremberg, Germany

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Brescia, Brescia, Italy

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Milan, Milano, Italy

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Guadalajara, Jalisco, Mexico

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Monterrey, Nuevo León, Mexico

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Bialystok, Poland

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Bydgoszcz, Poland

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Poznan, Poland

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Warsaw, Poland

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Bellville, South Africa

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Johannesburg, South Africa

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Pretoria, South Africa

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Somerset West, South Africa

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Seongnam-si, Gyenggi-go, South Korea

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Busan, South Korea

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Seoul, South Korea

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Elche, Altcante, Spain

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Barcelona, Barcelona, Spain

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Terrassa, Barcelona, Spain

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Madrid, Madrid, Spain

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Burgos, Spain

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MeSH Terms

Conditions

Alzheimer Disease; Dementia

Interventions

7-chloro-N-quinuclidin-3-yl-benzo(b)thiophene-2-carboxamide

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 21, 2013
• First Posted: October 25, 2013
• Study Start: October 1, 2013
• Primary Completion: January 1, 2017
• Study Completion: January 1, 2017
• Last Updated: May 3, 2016

Record last verified: 2015-09

Locations

DE (4); ES (5); CA (4); IT (2); ME (2); BE (3); PL (4); ZA (4); FR (4); KR (3); US (44); AU (3)