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

Phase 1

Completed

Conditions: Alzheimer's Disease
Central Nervous System Diseases

Interventions: Drug: EVP-6124 (0.1 mg/day)
Drug: EVP-6124 (1.0 mg/day)
Drug: EVP-6124 (0.3 mg/day)
Drug: Donepezil
Drug: Rivastigmine

Registration Number: NCT00766363

Lead Sponsor: FORUM Pharmaceuticals Inc

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 49

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
EVP-6124 (0.1 mg/day)	EVP-6124 (0.1 mg/day)	-
EVP-6124 (0.1 mg/day)	Donepezil	-
EVP-6124 (1.0 mg/day)	EVP-6124 (1.0 mg/day)	-
EVP-6124 (0.3 mg/day)	EVP-6124 (0.3 mg/day)	-
EVP-6124 (1.0 mg/day)	Donepezil	-
EVP-6124 (0.1 mg/day)	Rivastigmine	-
EVP-6124 (0.3 mg/day)	Donepezil	-
EVP-6124 (0.3 mg/day)	Rivastigmine	-
EVP-6124 (1.0 mg/day)	Rivastigmine	-
Placebo	Rivastigmine	-
Placebo	Donepezil	-

Primary Outcome Measures

Name	Time	Method
Safety and Tolerability of Multiple Doses of EVP-6124 or Placebo in Subjects With Alzheimer's Disease	Pre-treatment (Day -2) [or screening for physical examination] to Day 28 [or Day 35, for AEs only]	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

Name	Time	Method
EVP-6124 PK Data Following the First Dose of EVP-6124 - Maximum Concentration (Cmax)	24 hours	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)	24 hours	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])	24 hours	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)	24 hours	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)	24 hours	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])	24 hours	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)	24 hours	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)	24 hours	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])	24 hours	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

Trial Locations

Locations (4): Comprehensive Clinical Research
🇺🇸
Berlin, New Jersey, United States
Global Medical Institutes, LLC
🇺🇸
Princeton, New Jersey, United States
Pacific Research Network, Inc.
🇺🇸
San Diego, California, United States
MD Clinical
🇺🇸
Hallandale Beach, Florida, United States