Alzheimer Disease
Conditions
Brief summary
To test that LY450139, a gamma-secretase inhibitor, will reduce the rate of newly synthesize Amyloid Beta by determining the amount of newly synthesized 13C6 leucine-labeled Amyloid Beta in lumbar cerebrospinal fluid from LY450139 treated subjects compared with placebo treated subjects.
Interventions
DRUGLY450139
DRUGplacebo
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
21 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy volunteers: Men within the ages of 21 and 50
Exclusion criteria
* Have serious or unstable medical conditions * Have a history of serious infections affecting the brain or head trauma resulting in protracted loss of consciousness within the last 5 years or multiple episodes of head trauma * Have a history of primary or recurrent malignant disease * Have a recent laboratory result indicating a clinically significant laboratory abnormality as determined by the investigator * Have a history of chronic alcohol or drug abuse within the past 5 years * Have a known history of Human immunodeficiency virus (HIV), afebrile seizures, or clinically significant multiple drug allergies * Are judged clinically by the investigator to be at serious risk for suicide * Have electrocardiogram abnormalities obtained at visit 1 that in the opinion of the investigator are clinically significant * Use of prescription or over the counter medications that cannot safely be discontinued within 14 days prior to visit 2 * Have criteria that would preclude a LP such as allergy to all local anesthetics; have a local infection at the site of the LP or have any medical condition requiring treatment with warfarin or heparin. * Have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry. * Are investigator site personnel directly affiliated with this study and or immediate families. * Are Lilly employees
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To test hypothesis that LY450139, a gamma-secretase inhibitor, will reduce the rate of synthesis of 13C6-leucine-labeled Aβ (newly synthesized) in lumbar cerebrospinal fluid (CSF). | 0-36 hours post dose |
Secondary
| Measure | Time frame |
|---|---|
| To test the hypothesis that LY450139 has an effect on fractional clearance rate of Amyloid Beta assayed from CSF samples in LY450139-treated subjects compared to placebo-treated subjects. | 0-36 hours post dose |
| To study and evaluate other biomarkers, such as sAPPB and sAPPA that may enable drug effectiveness to be predicted. | 0-36 hours post dose |
| To measure concentrations of Amyloid Beta(1-40), Amyloid Beta(1-42), and leucine in CSF by mass spectrometry. | 0-36 hours post dose |
| To explore the relationship between Amyloid Beta plasma decrease and Amyloid Beta synthesis rate as determined by CSF measurements. | 0-36 hours post dose |
Countries
United States
Outcome results
None listed