Safety, Tolerability, and Pharmacokinetic Study of EVP-6124 in Patients With Alzheimer's Disease
This study has been completed.
Sponsor:
EnVivo Pharmaceuticals, Inc.
Collaborator:
INC Research
Information provided by (Responsible Party):
EnVivo Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT00766363
First received: October 1, 2008
Last updated: April 18, 2012
Last verified: April 2012
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Alzheimer's Disease Central Nervous System Diseases |
Drug: EVP-6124 (0.1 mg/day) Drug: EVP-6124 (0.3 mg/day) Drug: EVP-6124 (1.0 mg/day) Drug: Comparator: Placebo Drug: Donepezil Drug: Rivastigmine |
Phase 1 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment |
| 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 |
Resource links provided by NLM:
Genetics Home Reference related topics:
Alzheimer disease
Drug Information available for:
Donepezil hydrochloride
Donepezil
Rivastigmine
Rivastigmine tartrate
U.S. FDA Resources
Further study details as provided by EnVivo Pharmaceuticals, Inc.:
Primary Outcome Measures:
- 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)
Secondary Outcome Measures:
- 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
| Enrollment: | 49 |
| Study Start Date: | October 2008 |
| Study Completion Date: | March 2009 |
| Primary Completion Date: | March 2009 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
| Experimental: EVP-6124 (0.1 mg/day) |
Drug: EVP-6124 (0.1 mg/day)
EVP-6124 was administered as one 0.1 mg 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 (0.3 mg/day) |
Drug: EVP-6124 (0.3 mg/day)
EVP-6124 was administered as one 0.3 mg capsule every 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 (1.0 mg/day) |
Drug: EVP-6124 (1.0 mg/day)
EVP-6124 was administered as one 1.0 mg capsule every 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.
|
| Placebo Comparator: Placebo |
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.
|
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| Ages Eligible for Study: | 50 Years to 90 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00766363
Locations
| United States, California | |
| Pacific Research Network, Inc. | |
| San Diego, California, United States, 92103 | |
| United States, Florida | |
| MD Clinical | |
| Hallandale Beach, Florida, United States, 33009 | |
| United States, New Jersey | |
| Comprehensive Clinical Research | |
| Berlin, New Jersey, United States, 08009 | |
| Global Medical Institutes, LLC | |
| Princeton, New Jersey, United States, 08540 | |
Sponsors and Collaborators
EnVivo Pharmaceuticals, Inc.
INC Research
Investigators
| 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 |
More Information
No publications provided
| Responsible Party: | EnVivo Pharmaceuticals, Inc. |
| ClinicalTrials.gov Identifier: | NCT00766363 History of Changes |
| Other Study ID Numbers: | EVP-6124-007 |
| Study First Received: | October 1, 2008 |
| Results First Received: | June 16, 2011 |
| Last Updated: | April 18, 2012 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by EnVivo Pharmaceuticals, Inc.:
|
Alzheimer's Disease Central Nervous System Diseases Pharmacokinetics Cognition |
Additional relevant MeSH terms:
|
Alzheimer Disease Central Nervous System Diseases Nervous System Diseases Dementia Brain Diseases Tauopathies Neurodegenerative Diseases Delirium, Dementia, Amnestic, Cognitive Disorders Mental Disorders Rivastigmine Donepezil Nicotinic Agonists Cholinesterase Inhibitors |
Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Cholinergic Agents Neurotransmitter Agents Physiological Effects of Drugs Neuroprotective Agents Protective Agents Central Nervous System Agents Therapeutic Uses Cholinergic Agonists Nootropic Agents |
ClinicalTrials.gov processed this record on May 19, 2013