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

Study Overview
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Brief Summary
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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.

Official Title
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Assessment of LY450139-Mediated Inhibition of Amyloid Beta Formation Determined by 13C6-Leucine In Healthy Subjects

Conditions
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Alzheimer Disease

Intervention / Treatment
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* Drug: LY450139
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>100 mg LY 450139 oral | Drug: LY450139<br> <br> |
| Experimental: 2<br>140 mg LY450139 oral | Drug: LY450139<br> <br> |
| Experimental: 3<br>280 mg LY450139 oral | Drug: LY450139<br> <br> |
| Experimental: 4<br>Placebo | Drug: placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 Outcome Measures

| Outcome Measure | Measure Description | 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 |