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

FORUM Pharmaceuticals

Status and phase: Completed; Phase 2

Conditions: Alzheimer's Disease; Mild Cognitive Impairment

Treatments: Drug: Placebo; Drug: EVP-0962

Study type: Interventional

Funder types: Industry

Identifiers

NCT01661673

EVP-0962-002

Details and patient eligibility

About

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.

Full 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.

Enrollment: 52 patients

Sex: All

Ages: 45 to 85 years old

Volunteers: Accepts 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

52 participants in 5 patient groups, including a placebo group

Arm 1

Experimental group

Description:

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

Treatment:

Drug: EVP-0962

Arm 2

Experimental group

Description:

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

Treatment:

Drug: EVP-0962

Arm 3

Experimental group

Description:

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

Treatment:

Drug: EVP-0962

Arm 4

Experimental group

Description:

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

Treatment:

Drug: EVP-0962

Arm 5

Placebo Comparator group

Description:

Placebo orally administered for 14 days

Treatment:

Drug: Placebo