A Study of LY110140 in Healthy Japanese Male Participants

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteer
• Intervention / Treatment: Drug: LY110140; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 56
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Osaka, Japan, 532-0003
    • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

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

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Study record dates

Study Major Dates

• Study Start: April 1, 2012
• Primary Completion (Actual): September 1, 2012
• Study Completion (Actual): September 1, 2012

Study Registration Dates

• First Submitted: March 30, 2012
• First Submitted That Met QC Criteria: March 30, 2012
• First Posted (Estimate): April 2, 2012

Study Record Updates

• Last Update Posted (Estimate): February 10, 2014
• Last Update Submitted That Met QC Criteria: January 14, 2014
• Last Verified: January 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Cytochrome P-450 Enzyme Inhibitors; Antidepressive Agents, Second-Generation; Cytochrome P-450 CYP2D6 Inhibitors; Fluoxetine
• Other Study ID Numbers: 14638; B1Y-JE-HCLX (Other Identifier: Eli Lilly and Company)