A Study of LY110140 in Healthy Japanese Male Participants

• ClinicalTrials.gov Identifier: NCT01569126
• Recruitment Status: Completed
• First Posted: April 2, 2012
• Results First Posted: November 25, 2013
• Last Update Posted: February 10, 2014
• Sponsor: Eli Lilly and Company
• Information provided by (Responsible Party): Eli Lilly and Company

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Healthy Volunteer	Drug: LY110140; Drug: Placebo	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 56 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Basic Science
• Official Title: A Phase 1 Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of LY110140 in Healthy Japanese Male Subjects
• Study Start Date: April 2012
• Actual Primary Completion Date: September 2012
• Actual Study Completion Date: September 2012

Arms and Interventions

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 Name: 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 Name: 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 Name: 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 Name: 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 Name: Fluoxetine Hydrochloride, Prozac, Sarafem

Outcome Measures

Primary Outcome Measures :

1. Number of Participants With One or More Drug-Related Adverse Events (AEs) or Any Serious AEs During the Single-Dose (SD) Period [ Time Frame: Baseline up to Day 43 ]
   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.
2. Number of Participants With One or More Drug-Related Adverse Events (AEs) or Any Serious AEs During the Multiple-Dose (MD) Period [ Time Frame: Baseline up to Day 70 ]
   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.

Secondary Outcome Measures :

1. Pharmacokinetics: Maximum Observed Drug Concentration (Cmax) of Single Dose (SD) of LY110140 [ Time Frame: Predose up to Day 43 ]
   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.
2. Pharmacokinetics: Area Under the Concentration-Time Curve From Zero to Last Time Point [AUC(0-tlast)] of Single Dose (SD) of LY110140 [ Time Frame: Predose up to Day 43 ]
   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.
3. Pharmacokinetics: Area Under the Concentration-Time Curve From Zero to Infinity [AUC(0-infinity)] of Single Dose (SD) of LY110140 [ Time Frame: Predose up to Day 43 ]
   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.
4. Pharmacokinetics: Maximum Observed Drug Concentration (Cmax) of Multiple Doses (MD) of LY110140 [ Time Frame: Days 1 and 28 ]
   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.
5. Pharmacokinetics: Area Under the Concentration-Time Curve From Zero to 24 Hours [AUC(0-24)] of Multiple Doses (MD) of LY110140 [ Time Frame: Day 1 ]
   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.
6. Pharmacokinetics: Area Under the Concentration-Time Curve for Dosing Interval (Tau) at Steady State [AUC(Tau,Steady State)] of Multiple Doses (MD) of LY110140 [ Time Frame: Predose up to Day 28 ]
   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.
7. Change From Baseline in Bazett's and Fridericia's Corrected QT (QTcB and QTcF) Intervals [ Time Frame: Baseline, up to Day 43 (SD period) and Baseline, up to Day 70 (MD period) ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 20 Years to 55 Years (Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

Criteria

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.

Contacts and Locations

Locations

Japan

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.

Osaka, Japan, 532-0003

Sponsors and Collaborators

Eli Lilly and Company

Investigators

• Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST); Eli Lilly and Company

More Information

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT01569126
• Other Study ID Numbers: 14638; B1Y-JE-HCLX ( Other Identifier: Eli Lilly and Company )
• First Posted: April 2, 2012
• Results First Posted: November 25, 2013
• Last Update Posted: February 10, 2014
• Last Verified: January 2014

Additional relevant MeSH terms:

Fluoxetine; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Agents; Serotonin Agents; Physiological Effects of Drugs; Antidepressive Agents, Second-Generation; Antidepressive Agents; Psychotropic Drugs; Cytochrome P-450 CYP2D6 Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Enzyme Inhibitors