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
Overview
- Phase
- Phase 1
- Intervention
- EVP-6124 (0.1 mg/day)
- Conditions
- Alzheimer's Disease
- Sponsor
- FORUM Pharmaceuticals Inc
- Enrollment
- 49
- Locations
- 4
- Primary Endpoint
- Safety and Tolerability of Multiple Doses of EVP-6124 or Placebo in Subjects With Alzheimer's Disease
- Status
- Completed
- Last Updated
- 14 years ago
Overview
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.
Investigators
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
Arms & Interventions
EVP-6124 (0.1 mg/day)
Intervention: EVP-6124 (0.1 mg/day)
EVP-6124 (0.1 mg/day)
Intervention: Donepezil
EVP-6124 (0.1 mg/day)
Intervention: Rivastigmine
EVP-6124 (0.3 mg/day)
Intervention: EVP-6124 (0.3 mg/day)
EVP-6124 (0.3 mg/day)
Intervention: Donepezil
EVP-6124 (0.3 mg/day)
Intervention: Rivastigmine
EVP-6124 (1.0 mg/day)
Intervention: EVP-6124 (1.0 mg/day)
EVP-6124 (1.0 mg/day)
Intervention: Donepezil
EVP-6124 (1.0 mg/day)
Intervention: Rivastigmine
Placebo
Intervention: Donepezil
Placebo
Intervention: Rivastigmine
Outcomes
Primary Outcomes
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]
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 Outcomes
- EVP-6124 PK Data Following the First Dose of EVP-6124 - Maximum Concentration (Cmax)(24 hours)
- EVP-6124 PK Data Following the First Dose of EVP-6124 - Time to Maximum Concentration (Tmax)(24 hours)
- EVP-6124 PK Data Following the First Dose of EVP-6124 - Area Under the Curve (AUC[0-24 h])(24 hours)
- Donepezil PK Data Following the First Dose of EVP-6124 - Maximum Concentration (Cmax)(24 hours)
- Donepezil PK Data Following the First Dose of EVP-6124 - Time to Maximum Concentration (Tmax)(24 hours)
- Donepezil PK Data Following the First Dose of EVP-6124 - Area Under the Curve (AUC[0-24 h])(24 hours)
- Rivastigmine PK Data Following the First Dose of EVP-6124 - Maximum Concentration (Cmax)(24 hours)
- Rivastigmine PK Data Following the First Dose of EVP-6124 - Time to Maximum Concentration (Tmax)(24 hours)
- Rivastigmine PK Data Following the First Dose of EVP-6124 - Area Under the Curve (AUC[0-24 h])(24 hours)