A Safety Study of LY2811376 Single Doses in Healthy Subjects

Study Overview
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Brief Summary
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This is a Phase 1 study in healthy subjects to evaluate the safety and tolerability of LY2811376 single doses, how the body handles the drug, and the drug's effect on the body.

Detailed Description
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This is a Phase 1 study with 2 parts, both in healthy subjects. Part 1 is a subject- and investigator-blind, placebo-controlled, randomized, 3 period, crossover study. Part 1 will assess the safety and tolerability of LY2811376 single doses, how the body handles the drug, and the drug's effect on the body. Part 2 is a subject- and investigator-blind, placebo-controlled, randomized study to assess the safety and tolerability of a LY2811376 single dose, how the body handles the drug, and the drug's effect on the body including in cerebrospinal fluid.

Official Title
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Single-Ascending Dose, Safety, Tolerability, Pharmacokinetic, and Pharmacodynamic Study of LY2811376 in Healthy Subjects

Conditions
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Alzheimer's Disease

Intervention / Treatment
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* Drug: LY2811376
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy men and nonchild-bearing potential women 20 years or older Body mass index between 18-32kg/m2 Exclusion Criteria: Taking over-the-counter or prescription medication with the exception of vitamins or minerals or stable doses of thyroid or estrogen hormone replacement. Smoke more than 10 cigarettes per day. Consume more than 5 cups of coffee per day.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

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

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LY2811376 Part 1<br>LY2811376 (5 mg up to 500 mg); once a day or twice a day for 1 day in up to 3 periods. | Drug: LY2811376<br>* Oral capsules<br>|
| Placebo Comparator: Placebo Part 1<br>once a day or twice a day for 1 day in up to 3 periods. | Drug: Placebo<br>* Oral capsules<br>|
| Experimental: LY2811376 - Part 2 low dose<br>Single dose of LY2811376, dose determined by part 1 | Drug: LY2811376<br>* Oral capsules<br>|
| Experimental: LY2811376 - Part 2 high dose<br>Single dose of LY2811376, dose determined by part 1 | Drug: LY2811376<br>* Oral capsules<br>|
| Placebo Comparator: Placebo Part 2<br>single dose | Drug: Placebo<br>* Oral capsules<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Effects |  | Predose and up to Day 6 of each period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma concentration of LY2811376 (Cmax) |  | Predose and up to Day 6 of each period | 
| Plasma concentration of LY2811376 (AUC) |  | Predose and up to Day 6 of each period | 
| Amyloid beta 1-40 plasma concentrations |  | Predose and up to Day 6 of each period | 
| Cerebrospinal fluid (CSF) concentration of LY2811376 (Cmax) (Part 2 only) |  | Predose and up to 36 hours | 
| Cerebrospinal fluid (CSF) concentration of LY2811376 (AUC) (Part 2 only) |  | Predose and up to 36 hours | 
| Amyloid beta 1-40 cerebrospinal fluid CSF concentrations (Part 2 only) |  | Predose and up to 36 hours |