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Safety, Tolerability, Pharmacokinetics of EVP-0962 and Effects of EVP-0962 on Cerebral Spinal Fluid Amyloid Concentrations in Healthy Subjects and in Subjects With Mild Cognitive Impairment or Early Alzheimer's Disease

Primary Purpose

Mild Cognitive Impairment, Alzheimer's Disease

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
EVP-0962
Placebo
Sponsored by
FORUM Pharmaceuticals Inc
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Mild Cognitive Impairment

Eligibility Criteria

45 Years - 85 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • Part 1: Male and female subjects between the ages of 45 to 65 (inclusive) in good health with a BMI of 18-32 kg/m2 and negative urine drug screen of abuse test.
  • Part 2: Male and female subjects between the ages of 45 to 85 (inclusive), MRI/CT scans compatible with diagnosis of MCI or early AD, meets the classification of MCI due to AD as defined by the National Institute on Aging-Alzheimer's Association, and a BMI of 18-32 kg/m2(inclusive). Subjects must meet the following Cognitive criteria: Subject Memory Complaint, cognitive impairment in one or more areas, CDR-SB score less than or equal 1.0, MMSE greater than 24, and no impairment in social or occupational functioning.

Exclusion Criteria:

  • History of seizure disorder, symptomatic orthostatic hypotension, QTc values greater than 450 ms, positive drug screening tests
  • Pregnancy, nursing, (or if fertile female) not willing to utilize birth control measures during study
  • C-SSRS suicidal ideation score of 4 or 5
  • Unwilling to abstain from vigorous exercise
  • Concurrent disease other than MCI or early AD that is attributing to patient's cognitive impairment.
  • Lumbar spine X-rays show anatomic contraindications to lumbar puncture
  • History of spinal surgery or chronic low back pain
  • History of migraine headaches

Sites / Locations

  • Glendale Adventist Medical Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Experimental

Experimental

Experimental

Placebo Comparator

Arm Label

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Description

10 mg EVP-0962 Orally administered once daily for 14 days

50 mg EVP-0962 Orally administered once daily for 14 days

100 mg EVP-0962 Orally administered once daily for 14 days

200 mg EVP-0962 Orally administered once daily for 14 days

Placebo orally administered for 14 days

Outcomes

Primary Outcome Measures

The number of adverse experiences reported by subjects and/or observed by investigator and repeated clinical evaluations of physical examinations, vital signs, 12-lead ECG (electrocardiogram), and lab tests (hematology, chemistry, urinalysis)
To measure the rate of synthesis of Amyloid Beta in cerebral spinal fluid of healthy subjects
To measure the concentration of Amyloid Beta in cerebral spinal fluid

Secondary Outcome Measures

To measure the rate of synthesis of Amyloid Beta and steady-state levels in the cerebral spinal fluid in MCI or early Alzheimer's disease patients
To determine single-and repeat-dose EVP-0962 pharmacokinetics in cerebral spinal fluid and plasma

Full Information

First Posted
August 3, 2012
Last Updated
January 10, 2014
Sponsor
FORUM Pharmaceuticals Inc
Collaborators
Parexel
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1. Study Identification

Unique Protocol Identification Number
NCT01661673
Brief Title
Safety, Tolerability, Pharmacokinetics of EVP-0962 and Effects of EVP-0962 on Cerebral Spinal Fluid Amyloid Concentrations in Healthy Subjects and in Subjects With Mild Cognitive Impairment or Early Alzheimer's Disease
Official Title
Safety, Tolerability, Pharmacokinetics, and Effects of EVP-0962 on Cerebral Spinal Fluid Amyloid Concentrations in Healthy Subjects and in Subjects With Mild Cognitive Impairment or Early Alzheimer's Disease
Study Type
Interventional

2. Study Status

Record Verification Date
January 2014
Overall Recruitment Status
Completed
Study Start Date
November 2012 (undefined)
Primary Completion Date
October 2013 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
FORUM Pharmaceuticals Inc
Collaborators
Parexel

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
This study is being conducted to determine the safety, tolerability, pharmacokinetics, and effects of EVP-0962 on cerebral spinal fluid Amyloid concentrations in healthy subjects and in subjects with mild cognitive impairment or early Alzheimer's disease.
Detailed Description
This is a randomized, double-blind, sequential escalating repeat daily dose study conducted in two parts. The first part is being conducted in healthy subjects and will evaluate safety, tolerability, and pharmacokinetics and pharmacodynamics of escalating EVP-0962 doses (10, 50 100 and 200 mg) or matching placebo following once-daily administration for 14 days. The second part will evaluate the safety, tolerability and pharmacokinetics and pharmacodynamics of EVP-0962 following once-daily administration for 14 days in patients with mild cognitive impairment or early Alzheimer's disease at the dose level selected based on the available safety, pharmacokinetics and pharmacodynamics observations in the first part.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Mild Cognitive Impairment, Alzheimer's Disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
52 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm 1
Arm Type
Experimental
Arm Description
10 mg EVP-0962 Orally administered once daily for 14 days
Arm Title
Arm 2
Arm Type
Experimental
Arm Description
50 mg EVP-0962 Orally administered once daily for 14 days
Arm Title
Arm 3
Arm Type
Experimental
Arm Description
100 mg EVP-0962 Orally administered once daily for 14 days
Arm Title
Arm 4
Arm Type
Experimental
Arm Description
200 mg EVP-0962 Orally administered once daily for 14 days
Arm Title
Arm 5
Arm Type
Placebo Comparator
Arm Description
Placebo orally administered for 14 days
Intervention Type
Drug
Intervention Name(s)
EVP-0962
Intervention Description
Arms: 1,2,3,4
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Arm 5
Primary Outcome Measure Information:
Title
The number of adverse experiences reported by subjects and/or observed by investigator and repeated clinical evaluations of physical examinations, vital signs, 12-lead ECG (electrocardiogram), and lab tests (hematology, chemistry, urinalysis)
Time Frame
Screening (Day-45 to Day -1) through Day 23 (end of study visit)
Title
To measure the rate of synthesis of Amyloid Beta in cerebral spinal fluid of healthy subjects
Time Frame
0-36 hours post dose
Title
To measure the concentration of Amyloid Beta in cerebral spinal fluid
Time Frame
0-36 hours post dose
Secondary Outcome Measure Information:
Title
To measure the rate of synthesis of Amyloid Beta and steady-state levels in the cerebral spinal fluid in MCI or early Alzheimer's disease patients
Time Frame
0-36 hours post dose
Title
To determine single-and repeat-dose EVP-0962 pharmacokinetics in cerebral spinal fluid and plasma
Time Frame
0-36 hours post dose

10. Eligibility

Sex
All
Minimum Age & Unit of Time
45 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Part 1: Male and female subjects between the ages of 45 to 65 (inclusive) in good health with a BMI of 18-32 kg/m2 and negative urine drug screen of abuse test. Part 2: Male and female subjects between the ages of 45 to 85 (inclusive), MRI/CT scans compatible with diagnosis of MCI or early AD, meets the classification of MCI due to AD as defined by the National Institute on Aging-Alzheimer's Association, and a BMI of 18-32 kg/m2(inclusive). Subjects must meet the following Cognitive criteria: Subject Memory Complaint, cognitive impairment in one or more areas, CDR-SB score less than or equal 1.0, MMSE greater than 24, and no impairment in social or occupational functioning. Exclusion Criteria: History of seizure disorder, symptomatic orthostatic hypotension, QTc values greater than 450 ms, positive drug screening tests Pregnancy, nursing, (or if fertile female) not willing to utilize birth control measures during study C-SSRS suicidal ideation score of 4 or 5 Unwilling to abstain from vigorous exercise Concurrent disease other than MCI or early AD that is attributing to patient's cognitive impairment. Lumbar spine X-rays show anatomic contraindications to lumbar puncture History of spinal surgery or chronic low back pain History of migraine headaches
Facility Information:
Facility Name
Glendale Adventist Medical Center
City
Glendale
State/Province
California
ZIP/Postal Code
91206
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Safety, Tolerability, Pharmacokinetics of EVP-0962 and Effects of EVP-0962 on Cerebral Spinal Fluid Amyloid Concentrations in Healthy Subjects and in Subjects With Mild Cognitive Impairment or Early Alzheimer's Disease

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