- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00766363
Safety, Tolerability, and Pharmacokinetic Study of EVP-6124 in Patients With Alzheimer's Disease
A Randomized, Double-Blind, Placebo-Controlled, Ascending-Dose Phase 1b Safety Study of Three Different Doses of an Alpha-7 Nicotinic Acetylcholine Receptor Agonist (EVP-6124) or Placebo in Patients With Mild to Moderate Probable Alzheimer's Disease
Study Overview
Status
Detailed Description
This is a randomized, double-blind, placebo-controlled, Phase 1b safety study of three dose levels of EVP-6124 in subjects with mild or moderate Alzheimer's disease and who are taking an AChEI medication (donepezil or rivastigmine).
Study drug will be supplied as capsules and will be orally administered once daily for a total of 28 days. Eligible subjects will be admitted to an inpatient study unit on Day -2 (two days before the first dose of study drug is administered) and will remain confined to the inpatient study unit for a total of five days. Starting on Day 4, subjects will continue the study in the outpatient setting, with study visits on Days 7, 14, 21, and 28. Safety assessments, PK sampling, and cognitive testing will be performed inpatient and at each study visit.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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California
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San Diego, California, United States, 92103
- Pacific Research Network, Inc.
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Florida
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Hallandale Beach, Florida, United States, 33009
- MD Clinical
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New Jersey
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Berlin, New Jersey, United States, 08009
- Comprehensive Clinical Research
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Princeton, New Jersey, United States, 08540
- Global Medical Institutes, LLC
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- male and post-menopausal or surgically sterile female pts
- 50-90 yrs old, who meet clinical criteria for probable Alzheimer's disease (Mini-Mental State Examination of 18-26; Hachinski Ischemic Score ≤4)
- must be taking donepezil or rivastigmine for at least 3 mos.
Exclusion Criteria:
- Unstable medical condition that is clinically significant in the judgment of the investigator; major organ system dysfunction
- Untreated hypothyroidism
- Insufficiently controlled diabetes mellitus
- Diagnosis of major depression requiring antidepressant medications within the last 5 years
- Stroke within 6 months before screening, or concomitant with onset of dementia
- Certain concomitant medications
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Placebo Comparator: Placebo
|
Concomitant therapy with donepezil at a stable dose, taken daily at the same time or immediately after the assigned EVP-6124 dose.
Patients must have been taking concomitant therapy for at least 3 months prior to enrollment to be eligible for the study.
Concomitant therapy with rivastigmine at a stable dose, taken daily at the same time or immediately after the assigned EVP-6124 dose.
Patients must have been taking concomitant therapy for at least 3 months prior to enrollment to be eligible for the study.
Matching placebo was administered as one capsule per day for 28 days.
|
Experimental: EVP-6124 (0.1 mg/day)
|
EVP-6124 was administered as one 0.1 mg capsule per day for 28 days.
Concomitant therapy with donepezil at a stable dose, taken daily at the same time or immediately after the assigned EVP-6124 dose.
Patients must have been taking concomitant therapy for at least 3 months prior to enrollment to be eligible for the study.
Concomitant therapy with rivastigmine at a stable dose, taken daily at the same time or immediately after the assigned EVP-6124 dose.
Patients must have been taking concomitant therapy for at least 3 months prior to enrollment to be eligible for the study.
|
Experimental: EVP-6124 (0.3 mg/day)
|
Concomitant therapy with donepezil at a stable dose, taken daily at the same time or immediately after the assigned EVP-6124 dose.
Patients must have been taking concomitant therapy for at least 3 months prior to enrollment to be eligible for the study.
Concomitant therapy with rivastigmine at a stable dose, taken daily at the same time or immediately after the assigned EVP-6124 dose.
Patients must have been taking concomitant therapy for at least 3 months prior to enrollment to be eligible for the study.
EVP-6124 was administered as one 0.3 mg capsule every day for 28 days.
|
Experimental: EVP-6124 (1.0 mg/day)
|
Concomitant therapy with donepezil at a stable dose, taken daily at the same time or immediately after the assigned EVP-6124 dose.
Patients must have been taking concomitant therapy for at least 3 months prior to enrollment to be eligible for the study.
Concomitant therapy with rivastigmine at a stable dose, taken daily at the same time or immediately after the assigned EVP-6124 dose.
Patients must have been taking concomitant therapy for at least 3 months prior to enrollment to be eligible for the study.
EVP-6124 was administered as one 1.0 mg capsule every day for 28 days.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Safety and Tolerability of Multiple Doses of EVP-6124 or Placebo in Subjects With Alzheimer's Disease
Time Frame: Pre-treatment (Day -2) [or screening for physical examination] to Day 28 [or Day 35, for AEs only]
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All adverse experiences spontaneously reported by subject and/or observed by investigator and repeated clinical evaluation of physical examinations, vital signs, 12-lead ECG (electrocardiogram), ambulatory ECG, and laboratory tests (hematology/blood chemistry/urinalysis)
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Pre-treatment (Day -2) [or screening for physical examination] to Day 28 [or Day 35, for AEs only]
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
EVP-6124 PK Data Following the First Dose of EVP-6124 - Maximum Concentration (Cmax)
Time Frame: 24 hours
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EVP-6124 PK data; Maximum Concentration (Cmax); i.e, highest concentration of drug in plasma
|
24 hours
|
EVP-6124 PK Data Following the First Dose of EVP-6124 - Time to Maximum Concentration (Tmax)
Time Frame: 24 hours
|
EVP-6124 PK data; Time to Maximum Concentration (Tmax); i.e, amount of time required to reach highest concentration of drug in plasma
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24 hours
|
EVP-6124 PK Data Following the First Dose of EVP-6124 - Area Under the Curve (AUC[0-24 h])
Time Frame: 24 hours
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EVP-6124 PK data; Area Under the Curve (AUC[0-24 h]); i.e, area under the concentration-time plot
|
24 hours
|
Donepezil PK Data Following the First Dose of EVP-6124 - Maximum Concentration (Cmax)
Time Frame: 24 hours
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Donepezil PK data; Maximum Concentration (Cmax); i.e, highest concentration of donepezil (parent compound only) in plasma after dosing with EVP-6124
|
24 hours
|
Donepezil PK Data Following the First Dose of EVP-6124 - Time to Maximum Concentration (Tmax)
Time Frame: 24 hours
|
Donepezil PK data; Time to Maximum Concentration (Tmax); i.e, amount of time required to reach highest concentration of donepezil (parent compound only) in plasma after dosing with EVP-6124
|
24 hours
|
Donepezil PK Data Following the First Dose of EVP-6124 - Area Under the Curve (AUC[0-24 h])
Time Frame: 24 hours
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Donepezil PK data; Area Under the Curve (AUC[0-24 h]); i.e, area under the concentration-time plot for donepezil (parent compound only) after dosing with EVP-6124
|
24 hours
|
Rivastigmine PK Data Following the First Dose of EVP-6124 - Maximum Concentration (Cmax)
Time Frame: 24 hours
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Rivastigmine PK data; Maximum Concentration (Cmax); i.e, highest concentration of rivastigmine in plasma after dosing with EVP-6124
|
24 hours
|
Rivastigmine PK Data Following the First Dose of EVP-6124 - Time to Maximum Concentration (Tmax)
Time Frame: 24 hours
|
Rivastigmine PK data; Time to Maximum Concentration (Tmax); i.e, amount of time required to reach highest concentration of rivastigmine in plasma after dosing with EVP-6124
|
24 hours
|
Rivastigmine PK Data Following the First Dose of EVP-6124 - Area Under the Curve (AUC[0-24 h])
Time Frame: 24 hours
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Rivastigmine PK data; Area Under the Curve (AUC[0-24 h]); i.e, area under the concentration-time plot for rivastigmine after dosing with EVP-6124
|
24 hours
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: David R. Hassmann, D.O., Comprehensive Clinical Research
- Principal Investigator: Beth Safirstein, M.D., MD Clinical
- Principal Investigator: Stephen Thein, Ph.D., Pacific Research Network, Inc.
- Principal Investigator: Jeffrey Apter, M.D., Global Medical Institutes
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Mental Disorders
- Brain Diseases
- Neurocognitive Disorders
- Neurodegenerative Diseases
- Dementia
- Tauopathies
- Nervous System Diseases
- Alzheimer Disease
- Central Nervous System Diseases
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Cholinergic Agents
- Enzyme Inhibitors
- Neuroprotective Agents
- Protective Agents
- Nootropic Agents
- Cholinesterase Inhibitors
- Donepezil
- Rivastigmine
Other Study ID Numbers
- EVP-6124-007
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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