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

FORUM Pharmaceuticals

Status and phase: Completed; Phase 1

Conditions: Alzheimer's Disease; Central Nervous System Diseases

Treatments: Drug: Rivastigmine; Drug: Comparator: Placebo; Drug: EVP-6124 (1.0 mg/day); Drug: EVP-6124 (0.1 mg/day); Drug: EVP-6124 (0.3 mg/day); Drug: Donepezil

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT00766363

EVP-6124-007

Details and patient eligibility

About

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.

Full 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.

Enrollment: 49 patients

Sex: All

Ages: 50 to 90 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

49 participants in 4 patient groups, including a placebo group

EVP-6124 (0.1 mg/day)

Experimental group

Treatment:

Drug: Rivastigmine

Drug: EVP-6124 (0.1 mg/day)

Drug: Donepezil

EVP-6124 (0.3 mg/day)

Experimental group

Treatment:

Drug: Rivastigmine

Drug: EVP-6124 (0.3 mg/day)

Drug: Donepezil

EVP-6124 (1.0 mg/day)

Experimental group

Treatment:

Drug: Rivastigmine

Drug: EVP-6124 (1.0 mg/day)

Drug: Donepezil

Placebo

Placebo Comparator group

Treatment:

Drug: Rivastigmine

Drug: Comparator: Placebo

Drug: Donepezil