A Study of LY2886721 in Healthy Participants

Study Overview
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Brief Summary
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The purpose of this phase I study in healthy participants will be to evaluate the safety and tolerability of LY2886721 single and multiple doses, to evaluate how the body handles the drug, and to evaluate the drug's effect on the body.

Official Title
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Single- and Multiple-Dose, Safety, Tolerability, Pharmacokinetic, and Pharmacodynamic Study of LY2886721 in Healthy Subjects

Conditions
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Healthy Volunteers

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 non-childbearing potential women Body mass index (BMI) between 18.0 and 32.0 kilograms per square meter (kg/m^2) Are reliable and willing to make yourself available for the duration of the study and are willing to follow study procedures and research unit policies Exclusion Criteria: Taking over-the-counter or prescription medication with the exception of vitamins or minerals Smoke more than 10 cigarettes per day Drink more than 5 cups of caffeine containing beverages (for example, coffee, tea) 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: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Single oral dose and/or once daily (QD) oral dosing for 14 consecutive days | Drug: Placebo<br>* Administered orally.<br>|
| Experimental: 35 mg LY2886721<br>QD oral dosing for 14 consecutive days | Drug: LY2886721<br>* Administered orally.<br>|
| Experimental: 70 mg LY2886721<br>Single oral dose or single oral dose followed by QD oral dosing for 14 consecutive days | Drug: LY2886721<br>* Administered orally.<br>|
| Experimental: 140 mg LY2886721<br>Single oral dose | Drug: LY2886721<br>* Administered orally.<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 | Data presented are the number of participants who experienced treatment-emergent adverse events. A summary of serious adverse events and other non-serious adverse events, regardless of causality is reported in the Adverse Events module. | Predose up to Day 23 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics: Plasma Maximum Observed Concentration (Cmax) of LY2886721 |  | Day 1 predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours postdose | 
| Pharmacokinetics: Plasma Area Under the Concentration Versus Time Curve From Time 0 Extrapolated to Infinity (AUCinf) of LY2886721 |  | Day 1 predose and 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, and 96 hours postdose | 
| Pharmacokinetics: Plasma Maximum Observed Concentration at Steady State (Cmax,ss) of LY2886721 |  | Day 14 predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hours postdose | 
| Pharmacokinetics: Plasma Area Under the Concentration Versus Time Curve (AUC) of LY2886721 | AUC over the dosing interval at steady state (AUCtau,ss) is reported for participants who received multiple doses of LY2886721. | Day 14 predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, and 120 hours postdose | 
| Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid 1-40 Concentration at Day 15 | Least squares (LS) mean percent changes from baseline to Day 15 in CSF amyloid 1-40 concentrations for participants in Cohort B are reported. LS means were calculated from an analysis of covariance (ANCOVA) with treatment group and predose CSF amyloid 1-40 concentration as fixed effects. The 95% confidence interval (CI) of the percent change from baseline was computed by back-transforming the mean difference between endpoint and baseline. | Baseline, Day 15 | 
| Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid 1-40 Concentration at 24 Hours Post-dose | LS mean percent changes from baseline to 24 hours post-dose in CSF amyloid 1-40 concentrations for participants in Cohort C are reported. LS means were calculated from an ANCOVA with treatment group and predose CSF amyloid 1-40 concentration as fixed effects. The 95% CI of the percent change from baseline was computed by back-transforming the mean difference between endpoint and baseline. | Baseline, 24 hours post-dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mild Cognitive Impairment