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

Mild Cognitive Impairment Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01661673
• Other study ID #: EVP-0962-002
• Status: Completed
• Phase: Phase 2
• First received: August 3, 2012
• Last updated: January 10, 2014
• Start date: November 2012

Study information

• Verified date: January 2014
• Source: FORUM Pharmaceuticals Inc
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 52
• Est. primary completion date: October 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 45 Years to 85 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Alzheimer Disease
• Alzheimer's Disease
• Cognition Disorders
• Mild Cognitive Impairment

Intervention

Drug:
• EVP-0962
Arms: 1,2,3,4
• Placebo
Arm 5

Locations

Country	Name	City	State
United States	Glendale Adventist Medical Center	Glendale	California

Sponsors (2)

Lead Sponsor	Collaborator
FORUM Pharmaceuticals Inc	Parexel

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)		Screening (Day-45 to Day -1) through Day 23 (end of study visit)	Yes
Primary	To measure the rate of synthesis of Amyloid Beta in cerebral spinal fluid of healthy subjects		0-36 hours post dose	No
Primary	To measure the concentration of Amyloid Beta in cerebral spinal fluid		0-36 hours post dose	No
Secondary	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		0-36 hours post dose	No
Secondary	To determine single-and repeat-dose EVP-0962 pharmacokinetics in cerebral spinal fluid and plasma		0-36 hours post dose	No