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

• ClinicalTrials.gov Identifier: NCT01661673
• Recruitment Status: Completed
• First Posted: August 9, 2012
• Last Update Posted: January 13, 2014
• Sponsor: FORUM Pharmaceuticals Inc
• Collaborator: Parexel
• Information provided by (Responsible Party): FORUM Pharmaceuticals Inc

Tracking Information

• First Submitted Date: August 3, 2012
• First Posted Date: August 9, 2012
• Last Update Posted Date: January 13, 2014
• Study Start Date: November 2012
• Actual Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 6, 2012)

• 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) ]
• To measure the rate of synthesis of Amyloid Beta in cerebral spinal fluid of healthy subjects [ Time Frame: 0-36 hours post dose ]
• To measure the concentration of Amyloid Beta in cerebral spinal fluid [ Time Frame: 0-36 hours post dose ]

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: August 6, 2012)

• 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 ]
• To determine single-and repeat-dose EVP-0962 pharmacokinetics in cerebral spinal fluid and plasma [ Time Frame: 0-36 hours post dose ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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
• 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.
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment

Condition

• Mild Cognitive Impairment
• Alzheimer's Disease

Intervention

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

Study Arms

• Experimental: Arm 1
  10 mg EVP-0962 Orally administered once daily for 14 days
  Intervention: Drug: EVP-0962
• Experimental: Arm 2
  50 mg EVP-0962 Orally administered once daily for 14 days
  Intervention: Drug: EVP-0962
• Experimental: Arm 3
  100 mg EVP-0962 Orally administered once daily for 14 days
  Intervention: Drug: EVP-0962
• Experimental: Arm 4
  200 mg EVP-0962 Orally administered once daily for 14 days
  Intervention: Drug: EVP-0962
• Placebo Comparator: Arm 5
  Placebo orally administered for 14 days
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 6, 2012): 52
• Original Estimated Enrollment: Same as current
• Study Completion Date: Not Provided
• Actual Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 45 Years to 85 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01661673
• Other Study ID Numbers: EVP-0962-002
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: FORUM Pharmaceuticals Inc
• Study Sponsor: FORUM Pharmaceuticals Inc
• Collaborators: Parexel
• Investigators: Not Provided
• PRS Account: FORUM Pharmaceuticals Inc
• Verification Date: January 2014