A Safety Study of LY2886721 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 LY2886721 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 LY2886721 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 an LY2886721 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 LY2886721 in Healthy Subjects

Conditions
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Alzheimer's Disease

Intervention / Treatment
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* Drug: LY2886721
* 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 18-32 kilograms per square meter (kg/m^2) 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

Ages Eligible for Study
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Minimum Age: 20 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: LY2886721 Part 1: Cohort A/B<br>Single (7 milligram (mg), 15 mg, 25 mg, 35 mg) doses of LY2886721 administered orally in up to three of three study periods | Drug: LY2886721<br>* Oral capsules<br>|
| Placebo Comparator: Placebo Part 1: Cohort A/B<br>Single dose in up to 1 period | Drug: Placebo<br>* Oral capsules<br>|
| Experimental: LY2886721 Part 2: Cohort C<br>Single 10 mg dose of LY2886721, dose determined by Part 1 | Drug: LY2886721<br>* Oral capsules<br>|
| Experimental: LY2886721 Part 2: Cohort D<br>Single 35 mg dose of LY2886721, dose determined by Part 1 | Drug: LY2886721<br>* Oral capsules<br>|
| Placebo Comparator: Placebo Part 2: Cohort C/D<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 |
| --- | --- | --- |
| Number of Participants With Clinically Significant Effects (Adverse Events) | A summary of serious adverse events and other nonserious adverse events located in Reported Adverse Event section. To assess effect of food on pharmacokinetics of LY2886721, participants in Cohort B during Period 3 (1 period=8 days) of Part 1 fasted overnight for at least 8 hours prior to receiving a single 7-milligram (mg) oral dose of LY2886721 in the fed state (Part 1 - Fed). Participants in other LY2886721 groups received LY2886721 in fasted state. Due to crossover design in Part 1, results reported by treatment; thus, participants are included in multiple arms. | Predose to 10-14 days after final dose of study drug (up to 42 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Plasma Concentration (Cmax) of LY2886721 | To assess effect of food on pharmacokinetics of LY2886721, participants in Cohort B during Period 3 (1 period=8 days) of Part 1 fasted overnight for at least 8 hours prior to receiving a single 7-milligram (mg) oral dose of LY2886721 in the fed state (Part 1 - Fed). Participants in the other LY2886721 groups received LY2886721 in the fasted state. Due to the crossover design in Part 1, results are reported by treatment; therefore, participants are included in multiple arms. | 0, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 60 and 96 hours post-dose | 
| Plasma Concentration of LY2886721: Area Under the Concentration Versus Time Curve (AUC) | Pharmacokinetic AUC for LY2886721 from time 0 to infinity. To assess effect of food on pharmacokinetics of LY2886721, participants in Cohort B during Period 3 (1 period=8 days) of Part 1 fasted overnight for at least 8 hours prior to receiving a single 7-milligram (mg) oral dose of LY2886721 in the fed state (Part 1 - Fed). Participants in the other LY2886721 groups received LY2886721 in the fasted state. Due to the crossover design in Part 1, results are reported by treatment; therefore, participants are included in multiple arms. | 0, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 60 and 96 hours post-dose | 
| Pharmacodynamic Biomarker: Plasma Amyloid Beta (Aβ) 1-40 Concentration (Part 1 Only) | Plasma concentrations of Aβ1-40 were based on the lowest observed/measured concentration (Cnadir). To assess effect of food on pharmacokinetics of LY2886721, participants in Cohort B during Period 3 (1 period=8 days) of Part 1 fasted overnight for at least 8 hours prior to receiving a single 7-milligram (mg) oral dose of LY2886721 in the fed state (Part 1 - Fed). Participants in the other LY2886721 groups received LY2886721 in the fasted state. Due to the crossover design in Part 1, results are reported by treatment; therefore, participants are included in multiple arms. | 0, 0.5, 1, 2, 4, 6, 8, 12, 24, 36, 48, 60 and 96 hours post-dose | 
| Cerebrospinal Fluid (CSF) Maximum Observed Drug Concentration (Cmax) of LY2886721 (Part 2 Only) |  | Predose and up to 36 hours postdose | 
| Cerebrospinal Fluid (CSF) Pharmacodynamic Biomarker Amyloid Beta (Aβ) 1-40 Concentration (Part 2 Only) | CSF Aβ 1-40 concentration was based on the lowest observed/measured concentration (Cnadir). | Predose and up to 36 hours postdose | 
| Cerebrospinal Fluid (CSF) Area Under the Concentration Versus Time Curve (AUC) of LY2886721 (Part 2 Only) |  | Predose and up to 36 hours postdose |