Clinical trial NCT00766363: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Alzheimer's Disease
Central Nervous System Diseases
Keywords: Alzheimer's Disease
Central Nervous System Diseases
Pharmacokinetics
Cognition
Lead sponsor: FORUM Pharmaceuticals Inc
Sponsor class: INDUSTRY
Collaborators: name: Syneos Health
First posted: 2008-10-03
Enrollment: 49
Sex: ALL
Minimum age (years): 50
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Safety and Tolerability of Multiple Doses of EVP-6124 or Placebo in Subjects With Alzheimer's Disease
timeFrame: Pre-treatment (Day -2) [or screening for physical examination] to Day 28 [or Day 35, for AEs only]
Secondary outcomes:
measure: EVP-6124 PK Data Following the First Dose of EVP-6124 - Maximum Concentration (Cmax)
timeFrame: 24 hours
measure: EVP-6124 PK Data Following the First Dose of EVP-6124 - Time to Maximum Concentration (Tmax)
timeFrame: 24 hours
measure: EVP-6124 PK Data Following the First Dose of EVP-6124 - Area Under the Curve (AUC[0-24 h])
timeFrame: 24 hours
measure: Donepezil PK Data Following the First Dose of EVP-6124 - Maximum Concentration (Cmax)
timeFrame: 24 hours
measure: Donepezil PK Data Following the First Dose of EVP-6124 - Time to Maximum Concentration (Tmax)
timeFrame: 24 hours
measure: Donepezil PK Data Following the First Dose of EVP-6124 - Area Under the Curve (AUC[0-24 h])
timeFrame: 24 hours
measure: Rivastigmine PK Data Following the First Dose of EVP-6124 - Maximum Concentration (Cmax)
timeFrame: 24 hours
measure: Rivastigmine PK Data Following the First Dose of EVP-6124 - Time to Maximum Concentration (Tmax)
timeFrame: 24 hours
measure: Rivastigmine PK Data Following the First Dose of EVP-6124 - Area Under the Curve (AUC[0-24 h])
timeFrame: 24 hours
Other outcomes:
Locations:
city: San Diego
country: United States
facility: Pacific Research Network, Inc.
state: California
city: Hallandale Beach
country: United States
facility: MD Clinical
state: Florida
city: Berlin
country: United States
facility: Comprehensive Clinical Research
state: New Jersey
city: Princeton
country: United States
facility: Global Medical Institutes, LLC
state: New Jersey
Study officials:
affiliation: Comprehensive Clinical Research
name: David R. Hassmann, D.O.
role: PRINCIPAL_INVESTIGATOR
affiliation: MD Clinical
name: Beth Safirstein, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Pacific Research Network, Inc.
name: Stephen Thein, Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Global Medical Institutes
name: Jeffrey Apter, M.D.
role: PRINCIPAL_INVESTIGATOR
References: