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

Sponsor:	EnVivo Pharmaceuticals, Inc.
Collaborator:	INC Research Limited
Information provided by:	EnVivo Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:	NCT00766363

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 I

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

MedlinePlus related topics: Alzheimer's Disease Neurologic Diseases

Drug Information available for: E 2020 Donepezil Rivastigmine SDZ-ENA 713

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 Limited

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:	Maria Gawryl, Ph.D., Vice President, Regulatory Affairs & Drug Development, 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:	July 14, 2011
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 February 12, 2012