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

This study has been completed.
Sponsor:
Collaborator:
INC Research
Information provided by (Responsible Party):
FORUM Pharmaceuticals Inc
ClinicalTrials.gov Identifier:
NCT00766363
First received: October 1, 2008
Last updated: April 18, 2012
Last verified: April 2012

October 1, 2008
April 18, 2012
October 2008
March 2009   (final data collection date for primary outcome measure)
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] ] [ Designated as safety issue: Yes ]
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)
Safety and tolerability of three doses of EVP-6124 and placebo administered daily for 28 days to subjects with Alzheimer's disease who are receiving concomitant treatment with an AChEI medication (donepezil or rivastigmine) [ Time Frame: 28 days ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00766363 on ClinicalTrials.gov Archive Site
  • EVP-6124 PK Data Following the First Dose of EVP-6124 - Maximum Concentration (Cmax) [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
    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) [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
    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]) [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
    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) [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
    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) [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
    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]) [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
    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) [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
    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) [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
    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]) [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
    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
Cognitive function and drug to drug interaction [ Time Frame: 28 days ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
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

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.

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.

Interventional
Phase 1
Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
  • Alzheimer's Disease
  • Central Nervous System Diseases
  • 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.
  • Experimental: EVP-6124 (0.1 mg/day)
    Interventions:
    • Drug: EVP-6124 (0.1 mg/day)
    • Drug: Donepezil
    • Drug: Rivastigmine
  • Experimental: EVP-6124 (0.3 mg/day)
    Interventions:
    • Drug: EVP-6124 (0.3 mg/day)
    • Drug: Donepezil
    • Drug: Rivastigmine
  • Experimental: EVP-6124 (1.0 mg/day)
    Interventions:
    • Drug: EVP-6124 (1.0 mg/day)
    • Drug: Donepezil
    • Drug: Rivastigmine
  • Placebo Comparator: Placebo
    Interventions:
    • Drug: Comparator: Placebo
    • Drug: Donepezil
    • Drug: Rivastigmine
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
49
March 2009
March 2009   (final data collection date for primary outcome measure)

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
Both
50 Years to 90 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00766363
EVP-6124-007
No
FORUM Pharmaceuticals Inc
FORUM Pharmaceuticals Inc
INC Research
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
FORUM Pharmaceuticals Inc
April 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP