A Study of Healthy Subjects to Assess the Effect of LY450139 on Amyloid Beta Peptide Production Rate and or Dose Response.

Recruitment & Eligibility

Inclusion Criteria

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

Study & Design

Arm && Interventions

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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

Recruitment & Eligibility