Study of the Safety of Two Doses of Investigational Study Drug EVP-6124 in Subjects With Alzheimer's Disease Currently Receiving Memantine

NCT02246075 | Withdrawn Phase 2 DMC

• 1 other identifier: EVP-6124-027
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 2

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.

Conditions

Alzheimer's Disease; Dementia; Cognition

Keywords

Alzheimer's disease; Cognition; Alpha-7 nAChR

Outcome Measures

Primary Outcomes (1)

• 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

  Baseline to Day 168

Secondary Outcomes (1)

• Change from Baseline in the Mini-Mental State Examination (MMSE)

  Baseline to Day 168

Study Arms (3)

EVP-6124, low dose

EXPERIMENTAL

Low dose, Tablet, Once Daily, Day 1 through Day 168

Drug: EVP-6124

EVP-6124, high dose

EXPERIMENTAL

High dose, Tablet, Once Daily, Day 1 through Day 168

Drug: EVP-6124

EVP-6124, Placebo

PLACEBO COMPARATOR

Placebo, Tablet, Once Daily, Day 1 through Day 168

Drug: EVP-6124

Interventions

EVP-6124 DRUG

Also known as: encenicline

EVP-6124, Placebo; EVP-6124, high dose; EVP-6124, low dose

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 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.

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 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

Sponsors & Collaborators

• FORUM Pharmaceuticals Inc: lead
• Quintiles, Inc.: collaborator

Study Sites (2)

Unknown Facility

Delray Beach, Florida, United States

Location

Unknown Facility

Albuquerque, New Mexico, United States

Location

MeSH Terms

Conditions

Alzheimer Disease; Dementia

Interventions

7-chloro-N-quinuclidin-3-yl-benzo(b)thiophene-2-carboxamide; N-(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 2
• 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: September 17, 2014
• First Posted: September 22, 2014
• Study Start: July 1, 2015
• Primary Completion: October 1, 2016
• Last Updated: October 15, 2015

Record last verified: 2015-10

Locations

US (2)