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Safety, Tolerability, and Pharmacokinetic Study of EVP-6124 in Patients With Alzheimer's Disease

Primary Purpose

Alzheimer's Disease, Central Nervous System Diseases

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
EVP-6124 (0.1 mg/day)
EVP-6124 (0.3 mg/day)
EVP-6124 (1.0 mg/day)
Comparator: Placebo
Donepezil
Rivastigmine
Sponsored by
FORUM Pharmaceuticals Inc
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Alzheimer's Disease focused on measuring Alzheimer's Disease, Central Nervous System Diseases, Pharmacokinetics, Cognition

Eligibility Criteria

50 Years - 90 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Pacific Research Network, Inc.
  • MD Clinical
  • Comprehensive Clinical Research
  • Global Medical Institutes, LLC

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Placebo Comparator

Arm Label

EVP-6124 (0.1 mg/day)

EVP-6124 (0.3 mg/day)

EVP-6124 (1.0 mg/day)

Placebo

Arm Description

Outcomes

Primary Outcome Measures

Safety and Tolerability of Multiple Doses of EVP-6124 or Placebo in Subjects With Alzheimer's Disease
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)

Secondary Outcome Measures

EVP-6124 PK Data Following the First Dose of EVP-6124 - Maximum Concentration (Cmax)
EVP-6124 PK data; Maximum Concentration (Cmax); i.e, highest concentration of drug in plasma
EVP-6124 PK Data Following the First Dose of EVP-6124 - Time to Maximum Concentration (Tmax)
EVP-6124 PK data; Time to Maximum Concentration (Tmax); i.e, amount of time required to reach highest concentration of drug in plasma
EVP-6124 PK Data Following the First Dose of EVP-6124 - Area Under the Curve (AUC[0-24 h])
EVP-6124 PK data; Area Under the Curve (AUC[0-24 h]); i.e, area under the concentration-time plot
Donepezil PK Data Following the First Dose of EVP-6124 - Maximum Concentration (Cmax)
Donepezil PK data; Maximum Concentration (Cmax); i.e, highest concentration of donepezil (parent compound only) in plasma after dosing with EVP-6124
Donepezil PK Data Following the First Dose of EVP-6124 - Time to Maximum Concentration (Tmax)
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
Donepezil PK Data Following the First Dose of EVP-6124 - Area Under the Curve (AUC[0-24 h])
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
Rivastigmine PK Data Following the First Dose of EVP-6124 - Maximum Concentration (Cmax)
Rivastigmine PK data; Maximum Concentration (Cmax); i.e, highest concentration of rivastigmine in plasma after dosing with EVP-6124
Rivastigmine PK Data Following the First Dose of EVP-6124 - Time to Maximum Concentration (Tmax)
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
Rivastigmine PK Data Following the First Dose of EVP-6124 - Area Under the Curve (AUC[0-24 h])
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

Full Information

First Posted
October 1, 2008
Last Updated
April 18, 2012
Sponsor
FORUM Pharmaceuticals Inc
Collaborators
Syneos Health
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1. Study Identification

Unique Protocol Identification Number
NCT00766363
Brief Title
Safety, Tolerability, and Pharmacokinetic Study of EVP-6124 in Patients With Alzheimer's Disease
Official Title
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 Type
Interventional

2. Study Status

Record Verification Date
April 2012
Overall Recruitment Status
Completed
Study Start Date
October 2008 (undefined)
Primary Completion Date
March 2009 (Actual)
Study Completion Date
March 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
FORUM Pharmaceuticals Inc
Collaborators
Syneos Health

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
This study is being conducted to determine the safety, tolerability, and pharmacokinetics (PK) of three different doses of an investigational medication, EVP-6124, in individuals with mild to moderate Alzheimer's disease who are also taking an Alzheimer's medication (AChEI [acetylcholinesterase inhibitor]: either donepezil or rivastigmine). In addition, PK of AChEI medications will be assessed. Cognitive function will be evaluated on an exploratory basis.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alzheimer's Disease, Central Nervous System Diseases
Keywords
Alzheimer's Disease, Central Nervous System Diseases, Pharmacokinetics, Cognition

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
49 (Actual)

8. Arms, Groups, and Interventions

Arm Title
EVP-6124 (0.1 mg/day)
Arm Type
Experimental
Arm Title
EVP-6124 (0.3 mg/day)
Arm Type
Experimental
Arm Title
EVP-6124 (1.0 mg/day)
Arm Type
Experimental
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
EVP-6124 (0.1 mg/day)
Intervention Description
EVP-6124 was administered as one 0.1 mg capsule per day for 28 days.
Intervention Type
Drug
Intervention Name(s)
EVP-6124 (0.3 mg/day)
Intervention Description
EVP-6124 was administered as one 0.3 mg capsule every day for 28 days.
Intervention Type
Drug
Intervention Name(s)
EVP-6124 (1.0 mg/day)
Intervention Description
EVP-6124 was administered as one 1.0 mg capsule every day for 28 days.
Intervention Type
Drug
Intervention Name(s)
Comparator: Placebo
Intervention Description
Matching placebo was administered as one capsule per day for 28 days.
Intervention Type
Drug
Intervention Name(s)
Donepezil
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Rivastigmine
Intervention Description
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.
Primary Outcome Measure Information:
Title
Safety and Tolerability of Multiple Doses of EVP-6124 or Placebo in Subjects With Alzheimer's Disease
Description
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)
Time Frame
Pre-treatment (Day -2) [or screening for physical examination] to Day 28 [or Day 35, for AEs only]
Secondary Outcome Measure Information:
Title
EVP-6124 PK Data Following the First Dose of EVP-6124 - Maximum Concentration (Cmax)
Description
EVP-6124 PK data; Maximum Concentration (Cmax); i.e, highest concentration of drug in plasma
Time Frame
24 hours
Title
EVP-6124 PK Data Following the First Dose of EVP-6124 - Time to Maximum Concentration (Tmax)
Description
EVP-6124 PK data; Time to Maximum Concentration (Tmax); i.e, amount of time required to reach highest concentration of drug in plasma
Time Frame
24 hours
Title
EVP-6124 PK Data Following the First Dose of EVP-6124 - Area Under the Curve (AUC[0-24 h])
Description
EVP-6124 PK data; Area Under the Curve (AUC[0-24 h]); i.e, area under the concentration-time plot
Time Frame
24 hours
Title
Donepezil PK Data Following the First Dose of EVP-6124 - Maximum Concentration (Cmax)
Description
Donepezil PK data; Maximum Concentration (Cmax); i.e, highest concentration of donepezil (parent compound only) in plasma after dosing with EVP-6124
Time Frame
24 hours
Title
Donepezil PK Data Following the First Dose of EVP-6124 - Time to Maximum Concentration (Tmax)
Description
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
Time Frame
24 hours
Title
Donepezil PK Data Following the First Dose of EVP-6124 - Area Under the Curve (AUC[0-24 h])
Description
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
Time Frame
24 hours
Title
Rivastigmine PK Data Following the First Dose of EVP-6124 - Maximum Concentration (Cmax)
Description
Rivastigmine PK data; Maximum Concentration (Cmax); i.e, highest concentration of rivastigmine in plasma after dosing with EVP-6124
Time Frame
24 hours
Title
Rivastigmine PK Data Following the First Dose of EVP-6124 - Time to Maximum Concentration (Tmax)
Description
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
Time Frame
24 hours
Title
Rivastigmine PK Data Following the First Dose of EVP-6124 - Area Under the Curve (AUC[0-24 h])
Description
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
Time Frame
24 hours

10. Eligibility

Sex
All
Minimum Age & Unit of Time
50 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David R. Hassmann, D.O.
Organizational Affiliation
Comprehensive Clinical Research
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Beth Safirstein, M.D.
Organizational Affiliation
MD Clinical
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Stephen Thein, Ph.D.
Organizational Affiliation
Pacific Research Network, Inc.
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Jeffrey Apter, M.D.
Organizational Affiliation
Global Medical Institutes
Official's Role
Principal Investigator
Facility Information:
Facility Name
Pacific Research Network, Inc.
City
San Diego
State/Province
California
ZIP/Postal Code
92103
Country
United States
Facility Name
MD Clinical
City
Hallandale Beach
State/Province
Florida
ZIP/Postal Code
33009
Country
United States
Facility Name
Comprehensive Clinical Research
City
Berlin
State/Province
New Jersey
ZIP/Postal Code
08009
Country
United States
Facility Name
Global Medical Institutes, LLC
City
Princeton
State/Province
New Jersey
ZIP/Postal Code
08540
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Safety, Tolerability, and Pharmacokinetic Study of EVP-6124 in Patients With Alzheimer's Disease

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