Assessment of Safety, Tolerability, and Pharmacodynamic Effects of LY2886721 in Patients with Mild Cognitive Impairment Due to Alzheimer*s Disease or Mild Alzheimer's Disease

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 20

Inclusion Criteria

Inclusion Criteria:
Patients may be included in the study only if they meet all of the following criteria:
[1] Present with MCI due to AD or mild AD based on the disease diagnostic criteria (Section 8.1.1).
[2] Are men or postmenopausal women, at least 55 years of age. Postmenopausal women are defined as women who have had a hysterectomy and/or bilateral oophorectomy; or who have been amenorrheic for at least 2 years.
[3] Have a reliable caregiver/study informant who provides a separate written informed consent to participate and who is in frequent contact with the patient (defined as at least 10 hours per week). The caregiver/study informant must be able to communicate with site personnel and in the investigator*s opinion must have adequate literacy to complete the protocol-specified questionnaires. If a caregiver/study informant cannot continue, 1 replacement is allowed.
[4] Have adequate vision (have not met exclusion criteria 12) and hearing for neuropsychological testing in the opinion of the investigator
[5] Have adequate premorbid literacy in the investigator*s opinion to complete the required psychometric tests
[6] Have given written informed consent approved by Lilly and the ethical review board (ERB) governing the site

Exclusion Criteria

Exclusion Criteria:
Subjects will be excluded from the study if they meet any of the following criteria:
[7] Are currently enrolled in, or discontinued within the last 30 days from, a clinical trial involving an investigational product or nonapproved use of a drug or device (other than the investigational product used in this study), or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study
[8] Diagnosis or history of other possible etiology of dementia, including but not limited to other neurodegenerative disorders
[9] Has received acetylcholinesterase inhibitors (ACHEIs), memantine and/or other AD therapy for <2 months or has <4 weeks of stable therapy on these treatments by Visit 1, or, in the opinion of the investigator, the patient will not likely remain on stable treatment regimen for 6 months. Note: If a patient has recently stopped ACHEIs and/or memantine, he or she must have discontinued treatment at least 4 weeks before Visit 1. Patients not treated with anti-Alzheimer drugs are eligible for study enrollment.
[10] Has frontotemporal dementia, Lewy body disease, vascular dementia, Huntington*s Disease or concomitant Parkinson*s disease, progressive supranuclear palsy (PSNP) or other movement disorder, or active autoimmune or neuroimmunologic disorders causing dementia or cognitive impairment
[11] Has B12 <200 pg/ml (<148 pmol/L), or folate <7.5 nmol/L (<3.3 ng/ml) indicating vitamin deficiency
[12] Patients with significant retinal impairment:
morphological retinal impairment (based on the 3-field visual photography and, OCT).
• significant (moderate or severe) dry or any untreated wet age-related macular degeneration.
• other significant retinal diseases (such as diabetic retinopathy),
• retinal vascular occlusions that are visually significant
• clinically significant epiretinal membrane (or macular pucker) or a clinically significant macular hole
functional impairment, such as:
• corrected visual acuity less than 20/40 in each eye, as measured on the Snellen, ETDRS or equivalent chart
• VFQ-25, with a baseline global score of less than 70
• increased intraocular pressure (non-treated glaucoma)
Opthalmological diagnostic and exclusion criteria will be defined in Manual of Operations provided to the sites.
[13] Has a history within the past 5 years of a serious infectious disease affecting the brain, including meningitis, or encephalitis
[14] Severe or recurrent head injury that is clinically relevant to the disease under study, (that is, with permanent neurological/cognitive sequelae)
[15] Onset of dementia following heart surgery or cardiac arrest
[16] Abnormal thyroid function: Thyroid Stimulating Hormone (TSH) values are outside of the normal range 0.3-5.6 mIU/L. (NOTE: patients with stable treatment of hypothyroidism and with normal value of TSH will be allowed to enter the study).
[17] Diagnosis or history of cerebrovascular disease (for example, stroke, transient ischemic attack), severe carotid stenosis, cerebral hemorrhage, intracranial tumor, subarachnoid hemorrhage, or subdural hematoma that could contribute to the subject's current cognitive or functional status, impair ability to fully participate in the trial or that may impact health status.
[18] Has had a PET scan within 6 months of the scheduled imaging at Visit 2;[19] Are being monitored fo

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>The primary objective:<br /><br>To assess the cerebrospinal fluid (CSF) pharmacodynamic (FD) effect of<br /><br>different LY2886721 doses in patients with mild cognitive impairment (MCI) due<br /><br>to Alzheimer*s Disease (AD) or mild AD compared to placebo, measured by change<br /><br>of CSF Aβ1-40 and Aβ1-42 concentrations from baseline to Week 12 and Week 26.</p><br>

Secondary Outcome Measures

Name	Time	Method