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

Brief Summary

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”

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.

  • Study Type: Interventional
  • Study Design: Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
  • Study Primary Completion Date: March 2009

Detailed Clinical Trial 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.

Interventions Used in this Clinical Trial

  • Drug: EVP-6124 (0.1 mg/day)
    • EVP-6124 was administered as one 0.1 mg capsule per day for 28 days.
  • Drug: EVP-6124 (0.3 mg/day)
    • EVP-6124 was administered as one 0.3 mg capsule every day for 28 days.
  • Drug: EVP-6124 (1.0 mg/day)
    • EVP-6124 was administered as one 1.0 mg capsule every day for 28 days.
  • Drug: Comparator: Placebo
    • Matching placebo was administered as one capsule per day for 28 days.
  • 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.
  • 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.

Arms, Groups and Cohorts in this Clinical Trial

  • Experimental: EVP-6124 (0.1 mg/day)
  • Experimental: EVP-6124 (0.3 mg/day)
  • Experimental: EVP-6124 (1.0 mg/day)
  • Placebo Comparator: Placebo

Outcome Measures for this Clinical Trial

Primary Measures

  • 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]
      Safety Issue?: Yes

Secondary Measures

  • EVP-6124 PK Data Following the First Dose of EVP-6124 – Maximum Concentration (Cmax)
    • Time Frame: 24 hours
      Safety Issue?: No
  • EVP-6124 PK Data Following the First Dose of EVP-6124 – Time to Maximum Concentration (Tmax)
    • Time Frame: 24 hours
      Safety Issue?: No
  • EVP-6124 PK Data Following the First Dose of EVP-6124 – Area Under the Curve (AUC[0-24 h])
    • Time Frame: 24 hours
      Safety Issue?: No
  • Donepezil PK Data Following the First Dose of EVP-6124 – Maximum Concentration (Cmax)
    • Time Frame: 24 hours
      Safety Issue?: No
  • Donepezil PK Data Following the First Dose of EVP-6124 – Time to Maximum Concentration (Tmax)
    • Time Frame: 24 hours
      Safety Issue?: No
  • Donepezil PK Data Following the First Dose of EVP-6124 – Area Under the Curve (AUC[0-24 h])
    • Time Frame: 24 hours
      Safety Issue?: No
  • Rivastigmine PK Data Following the First Dose of EVP-6124 – Maximum Concentration (Cmax)
    • Time Frame: 24 hours
      Safety Issue?: No
  • Rivastigmine PK Data Following the First Dose of EVP-6124 – Time to Maximum Concentration (Tmax)
    • Time Frame: 24 hours
      Safety Issue?: No
  • Rivastigmine PK Data Following the First Dose of EVP-6124 – Area Under the Curve (AUC[0-24 h])
    • Time Frame: 24 hours
      Safety Issue?: No

Criteria for Participation in this Clinical Trial

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 50 Years

Maximum Age for this Clinical Trial: 90 Years

Are Healthy Volunteers Accepted for this Clinical Trial: No

Clinical Trial Investigator Information

  • Lead Sponsor
    • FORUM Pharmaceuticals Inc
  • Collaborator
    • INC Research
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • David R. Hassmann, D.O., Principal Investigator, Comprehensive Clinical Research
    • Beth Safirstein, M.D., Principal Investigator, MD Clinical
    • Stephen Thein, Ph.D., Principal Investigator, Pacific Research Network, Inc.
    • Jeffrey Apter, M.D., Principal Investigator, Global Medical Institutes

Source

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The URL of this page is:
http://clinicaltrialsfeeds.org/clinical-trials/show/NCT00766363