A Study of LY110140 in Healthy Japanese Male Participants

Study Overview
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Brief Summary
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The purposes of this study are to look at safety, how well the study drug (LY110140) is tolerated, and how much of the study drug gets into the blood stream when given as single dose (SD) and multiple doses (MD) to healthy Japanese male participants. Participants will participate in SD portion for approximately 6 weeks and in MD portion for approximately 10 weeks.

Official Title
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A Phase 1 Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of LY110140 in Healthy Japanese Male Subjects

Conditions
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Healthy Volunteer

Intervention / Treatment
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* Drug: LY110140
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Overtly healthy Japanese males (as determined by medical history and physical examination) who agree to use a reliable method of birth control during the study and for 3 months following the last dose of the investigational product. Have a body mass index (BMI) of 18.5 to 29.9 kilograms per square meter (kg/m^2), inclusive, at the time of screening. Have given written informed consent approved by Lilly and the ethical review board (ERB) governing the study site. Exclusion Criteria: Poor metabolizers of isoenzyme cytochrome P450 2D6 (CYP2D6) (assessed at screening). Have an abnormality in the 12-lead electrocardiogram (ECG) at screening that, in the opinion of the investigator, increases the risks associated with participating in the study such as, a Bazett's corrected QT (QTcB) interval >450 milliseconds (msec). Have any lifetime history of a suicide attempt, or have suicidal ideation or, any suicidal behavior within the last month, or who are at significant risk to commit suicide, as judged by the investigator using the Columbia Suicide Severity Rating Scale (C-SSRS). Are unsuitable (in the opinion of the investigator or sponsor) for inclusion in the study.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 55 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

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 5 milligrams (mg) LY110140 (SD)<br>5 mg administered once in the fasted state on Day 1 | Drug: LY110140<br>* Administered orally as capsules<br>* Other names: Fluoxetine Hydrochloride, Prozac, Sarafem;|
| Experimental: 20 mg LY110140 (SD)<br>20 mg administered once in the fasted state on Day 1 | Drug: LY110140<br>* Administered orally as capsules<br>* Other names: Fluoxetine Hydrochloride, Prozac, Sarafem;|
| Experimental: 40 mg LY110140 (SD)<br>40 mg administered once in the fasted state on Day 1 | Drug: LY110140<br>* Administered orally as capsules<br>* Other names: Fluoxetine Hydrochloride, Prozac, Sarafem;|
| Placebo Comparator: Placebo (MD)<br>Placebo once daily oral dosing for 28 consecutive days | Drug: Placebo<br>* Administered orally as capsules in the placebo arm and to maintain the blind in the 20 mg LY110140 (MD) arm<br>|
| Experimental: 20 mg LY110140 (MD)<br>20 mg once daily oral dosing for 28 consecutive days | Drug: LY110140<br>* Administered orally as capsules<br>* Other names: Fluoxetine Hydrochloride, Prozac, Sarafem;|
| Experimental: 40 mg LY110140 (MD)<br>40 mg once daily oral dosing for 28 consecutive days | Drug: LY110140<br>* Administered orally as capsules<br>* Other names: Fluoxetine Hydrochloride, Prozac, Sarafem;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With One or More Drug-Related Adverse Events (AEs) or Any Serious AEs During the Single-Dose (SD) Period | A drug-related AE was an AE that occurred postdose or was present predose and became more severe postdose and was considered to be related to study treatment. A summary of AEs, regardless of causality, is located in the Reported Adverse Events module. | Baseline up to Day 43 | 
| Number of Participants With One or More Drug-Related Adverse Events (AEs) or Any Serious AEs During the Multiple-Dose (MD) Period | A drug-related AE was an AE that occurred postdose or was present predose and became more severe postdose and was considered to be related to study treatment. A summary of AEs, regardless of causality, is located in the Reported Adverse Events module. | Baseline up to Day 70 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics: Maximum Observed Drug Concentration (Cmax) of Single Dose (SD) of LY110140 | Study drug was administered as LY110140 (fluoxetine hydrochloride) and its active portion, fluoxetine, was metabolized to norfluoxetine in the body. The Cmax of plasma total fluoxetine and norfluoxetine during the SD period is reported. | Predose up to Day 43 | 
| Pharmacokinetics: Area Under the Concentration-Time Curve From Zero to Last Time Point [AUC(0-tlast)] of Single Dose (SD) of LY110140 | Study drug was administered as LY110140 (fluoxetine hydrochloride) and its active portion, fluoxetine, was metabolized to norfluoxetine in the body. The AUC(0-tlast) of plasma total fluoxetine and norfluoxetine during the SD period is reported. | Predose up to Day 43 | 
| Pharmacokinetics: Area Under the Concentration-Time Curve From Zero to Infinity [AUC(0-infinity)] of Single Dose (SD) of LY110140 | Study drug was administered as LY110140 (fluoxetine hydrochloride) and its active portion, fluoxetine, was metabolized to norfluoxetine in the body. The AUC(0-infinity) of plasma total fluoxetine and norfluoxetine during the SD period is reported. | Predose up to Day 43 | 
| Pharmacokinetics: Maximum Observed Drug Concentration (Cmax) of Multiple Doses (MD) of LY110140 | Study drug was administered as LY110140 (fluoxetine hydrochloride) and its active portion, fluoxetine, was metabolized to norfluoxetine in the body. The Cmax of plasma total fluoxetine and norfluoxetine on Day 1 and Day 28 of the MD period is reported. | Days 1 and 28 | 
| Pharmacokinetics: Area Under the Concentration-Time Curve From Zero to 24 Hours [AUC(0-24)] of Multiple Doses (MD) of LY110140 | Study drug was administered as LY110140 (fluoxetine hydrochloride) and its active portion, fluoxetine, was metabolized to norfluoxetine in the body. The AUC(0-24) of plasma total fluoxetine and norfluoxetine on Day 1 of the MD period is reported. | Day 1 | 
| Pharmacokinetics: Area Under the Concentration-Time Curve for Dosing Interval (Tau) at Steady State [AUC(Tau,Steady State)] of Multiple Doses (MD) of LY110140 | Study drug was administered as LY110140 (fluoxetine hydrochloride) and its active portion, fluoxetine, was metabolized to norfluoxetine in the body. The AUC(tau,steady state) of plasma total fluoxetine and norfluoxetine during the MD period is reported. | Predose up to Day 28 | 
| Change From Baseline in Bazett's and Fridericia's Corrected QT (QTcB and QTcF) Intervals | The number of participants with a maximum increase from baseline in 12-lead electrocardiogram (ECG) QTcB and QTcF intervals >30 milliseconds (ms) and >60 ms for the single-dose (SD) and multiple-dose (MD) periods is reported. | Baseline, up to Day 43 (SD period) and Baseline, up to Day 70 (MD period) |