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

NCT ID: NCT00766363

Last Updated: 2012-04-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 49 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-10-31
• Study Completion Date: 2009-03-31

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.

Conditions

Alzheimer's Disease; Central Nervous System Diseases

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

EVP-6124 (0.1 mg/day)

Group Type: EXPERIMENTAL

EVP-6124 (0.1 mg/day)

Intervention Type: DRUG

EVP-6124 was administered as one 0.1 mg capsule per day for 28 days.

Donepezil

Intervention Type: DRUG

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.

Rivastigmine

Intervention Type: DRUG

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 (0.3 mg/day)

Group Type: EXPERIMENTAL

EVP-6124 (0.3 mg/day)

Intervention Type: DRUG

EVP-6124 was administered as one 0.3 mg capsule every day for 28 days.

Donepezil

Intervention Type: DRUG

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.

Rivastigmine

Intervention Type: DRUG

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 (1.0 mg/day)

Group Type: EXPERIMENTAL

EVP-6124 (1.0 mg/day)

Intervention Type: DRUG

EVP-6124 was administered as one 1.0 mg capsule every day for 28 days.

Donepezil

Intervention Type: DRUG

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.

Rivastigmine

Intervention Type: DRUG

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.

Placebo

Group Type: PLACEBO_COMPARATOR

Comparator: Placebo

Intervention Type: DRUG

Matching placebo was administered as one capsule per day for 28 days.

Donepezil

Intervention Type: DRUG

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.

Rivastigmine

Intervention Type: DRUG

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.

Interventions

EVP-6124 (0.1 mg/day)

EVP-6124 was administered as one 0.1 mg capsule per day for 28 days.

Intervention Type: DRUG

EVP-6124 (0.3 mg/day)

EVP-6124 was administered as one 0.3 mg capsule every day for 28 days.

Intervention Type: DRUG

EVP-6124 (1.0 mg/day)

EVP-6124 was administered as one 1.0 mg capsule every day for 28 days.

Intervention Type: DRUG

Comparator: Placebo

Matching placebo was administered as one capsule per day for 28 days.

Intervention Type: DRUG

Donepezil

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

Rivastigmine

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.

Intervention Type: DRUG

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

• Minimum Eligible Age: 50 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Syneos Health

OTHER

Sponsor Role: collaborator

FORUM Pharmaceuticals Inc

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

David R. Hassmann, D.O.

Role: PRINCIPAL_INVESTIGATOR

Comprehensive Clinical Research

Beth Safirstein, M.D.

Role: PRINCIPAL_INVESTIGATOR

MD Clinical

Stephen Thein, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Pacific Research Network, Inc.

Jeffrey Apter, M.D.

Role: PRINCIPAL_INVESTIGATOR

Global Medical Institutes

Locations

Pacific Research Network, Inc.

San Diego, California, United States

MD Clinical

Hallandale, Florida, United States

Comprehensive Clinical Research

Berlin, New Jersey, United States

Global Medical Institutes, LLC

Princeton, New Jersey, United States

Countries

United States

Other Identifiers

EVP-6124-007

Identifier Type: -

Identifier Source: org_study_id