Healthy Volunteer
Conditions
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.
Interventions
DRUGLY110140
Administered orally as capsules
DRUGPlacebo
Administered orally as capsules in the placebo arm and to maintain the blind in the 20 mg LY110140 (MD) arm
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
20 Years to 55 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With One or More Drug-Related Adverse Events (AEs) or Any Serious AEs During the Single-Dose (SD) Period | 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. |
| Number of Participants With One or More Drug-Related Adverse Events (AEs) or Any Serious AEs During the Multiple-Dose (MD) Period | 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
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics: Area Under the Concentration-Time Curve From Zero to Infinity [AUC(0-infinity)] of Single Dose (SD) of LY110140 | 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. |
| Pharmacokinetics: Maximum Observed Drug Concentration (Cmax) of Multiple Doses (MD) of LY110140 | 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. |
| Pharmacokinetics: Maximum Observed Drug Concentration (Cmax) of Single Dose (SD) of LY110140 | 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. |
| Pharmacokinetics: Area Under the Concentration-Time Curve for Dosing Interval (Tau) at Steady State [AUC(Tau,Steady State)] of Multiple Doses (MD) of LY110140 | 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. |
| Change From Baseline in Bazett's and Fridericia's Corrected QT (QTcB and QTcF) Intervals | 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. |
| Pharmacokinetics: Area Under the Concentration-Time Curve From Zero to 24 Hours [AUC(0-24)] of Multiple Doses (MD) of LY110140 | 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. |
| Pharmacokinetics: Area Under the Concentration-Time Curve From Zero to Last Time Point [AUC(0-tlast)] of Single Dose (SD) of LY110140 | 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. |
Countries
Japan
Participant flow
Pre-assignment details
The study consisted of 2 parts: the open-label, single-dose (SD) period which included 3 cohorts (Cohorts 1 to 3) and the placebo-controlled, multiple-dose (MD) period which included 2 cohorts (Cohorts 4 and 5).
Participants by arm
| Arm | Count |
|---|---|
| 5 mg LY110140 (SD) Cohort 1: 5-milligram (mg) LY110140 (fluoxetine hydrochloride) capsule orally administered once, in a fasted state, during the SD period. | 8 |
| 20 mg LY110140 (SD) Cohort 2: 20-mg LY110140 (fluoxetine hydrochloride) capsule orally administered once, in a fasted state, during the SD period. | 8 |
| 40 mg LY110140 (SD) Cohort 3: 40-mg LY110140 (fluoxetine hydrochloride) dose (two 20-mg LY110140 capsules) orally administered once, in a fasted state, during the SD period. | 8 |
| Placebo (MD) Participants, in Cohorts 4 and 5, who received a placebo capsule, orally administered once daily for 28 days, during the MD period. On Days 1 and 28 participants were required to fast at least 8 hours prior to dosing and 4 hours postdose. | 8 |
| 20 mg LY110140 (MD) Participants, in Cohort 4, who received 20-mg LY110140 (fluoxetine hydrochloride) capsule, orally administered once daily for 28 days, during the MD period. On Days 1 and 28, participants were required to fast at least 8 hours prior to dosing and 4 hours postdose. | 12 |
| 40 mg LY110140 (MD) Participants, in Cohort 5, who received two 20-mg LY110140 (fluoxetine hydrochloride) capsules, orally administered once daily for 28 days, during the MD period. On Days 1 and 28, participants were required to fast at least 8 hours prior to dosing and 4 hours postdose. | 12 |
| Total | 56 |
Baseline characteristics
| Characteristic | 5 mg LY110140 (SD) | 20 mg LY110140 (SD) | 40 mg LY110140 (SD) | Placebo (MD) | 20 mg LY110140 (MD) | 40 mg LY110140 (MD) | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 27.1 years STANDARD_DEVIATION 4.4 | 25.8 years STANDARD_DEVIATION 2.4 | 24.6 years STANDARD_DEVIATION 2.4 | 27.1 years STANDARD_DEVIATION 4.4 | 25.8 years STANDARD_DEVIATION 6.3 | 28.7 years STANDARD_DEVIATION 6.2 | 26.6 years STANDARD_DEVIATION 4.9 |
| Cytochrome P450 2D6 (CYP2D6) intermediate and extensive metabolizers CYP2D6 extensive metabolizers | 4 participants | 4 participants | 4 participants | 4 participants | 6 participants | 6 participants | 28 participants |
| Cytochrome P450 2D6 (CYP2D6) intermediate and extensive metabolizers CYP2D6 intermediate metabolizers | 4 participants | 4 participants | 4 participants | 4 participants | 6 participants | 6 participants | 28 participants |
| Race/Ethnicity, Customized Japanese | 8 participants | 8 participants | 8 participants | 8 participants | 12 participants | 12 participants | 56 participants |
| Region of Enrollment Japan | 8 participants | 8 participants | 8 participants | 8 participants | 12 participants | 12 participants | 56 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 8 Participants | 8 Participants | 8 Participants | 8 Participants | 12 Participants | 12 Participants | 56 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 8 | 1 / 8 | 2 / 8 | 3 / 8 | 3 / 12 | 6 / 12 |
| serious Total, serious adverse events | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 12 | 0 / 12 |
Outcome results
Primary
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.
Time frame: Baseline up to Day 70
Population: Randomized participants, in Cohorts 4 and 5, who received at least 1 dose of study drug or placebo and had at least 1 postdose safety assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 5 mg LY110140 (SD) | Number of Participants With One or More Drug-Related Adverse Events (AEs) or Any Serious AEs During the Multiple-Dose (MD) Period | Drug-Related AE | 1 participants |
| 5 mg LY110140 (SD) | Number of Participants With One or More Drug-Related Adverse Events (AEs) or Any Serious AEs During the Multiple-Dose (MD) Period | Any Serious AE | 0 participants |
| 20 mg LY110140 (SD) | Number of Participants With One or More Drug-Related Adverse Events (AEs) or Any Serious AEs During the Multiple-Dose (MD) Period | Drug-Related AE | 0 participants |
| 20 mg LY110140 (SD) | Number of Participants With One or More Drug-Related Adverse Events (AEs) or Any Serious AEs During the Multiple-Dose (MD) Period | Any Serious AE | 0 participants |
| 40 mg LY110140 (SD) | Number of Participants With One or More Drug-Related Adverse Events (AEs) or Any Serious AEs During the Multiple-Dose (MD) Period | Drug-Related AE | 2 participants |
| 40 mg LY110140 (SD) | Number of Participants With One or More Drug-Related Adverse Events (AEs) or Any Serious AEs During the Multiple-Dose (MD) Period | Any Serious AE | 0 participants |
Primary
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.
Time frame: Baseline up to Day 43
Population: Randomized participants, in Cohorts 1, 2, and 3, who received at least 1 dose of study drug and had at least 1 postdose safety assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 5 mg LY110140 (SD) | Number of Participants With One or More Drug-Related Adverse Events (AEs) or Any Serious AEs During the Single-Dose (SD) Period | Drug-Related AE | 0 participants |
| 5 mg LY110140 (SD) | Number of Participants With One or More Drug-Related Adverse Events (AEs) or Any Serious AEs During the Single-Dose (SD) Period | Any Serious AE | 0 participants |
| 20 mg LY110140 (SD) | Number of Participants With One or More Drug-Related Adverse Events (AEs) or Any Serious AEs During the Single-Dose (SD) Period | Drug-Related AE | 0 participants |
| 20 mg LY110140 (SD) | Number of Participants With One or More Drug-Related Adverse Events (AEs) or Any Serious AEs During the Single-Dose (SD) Period | Any Serious AE | 0 participants |
| 40 mg LY110140 (SD) | Number of Participants With One or More Drug-Related Adverse Events (AEs) or Any Serious AEs During the Single-Dose (SD) Period | Drug-Related AE | 0 participants |
| 40 mg LY110140 (SD) | Number of Participants With One or More Drug-Related Adverse Events (AEs) or Any Serious AEs During the Single-Dose (SD) Period | Any Serious AE | 0 participants |
Secondary
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.
Time frame: Baseline, up to Day 43 (SD period) and Baseline, up to Day 70 (MD period)
Population: Randomized participants, in Cohorts 1, 2, and 3, who received at least 1 dose of study drug and had at least 1 postdose safety assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 5 mg LY110140 (SD) | Change From Baseline in Bazett's and Fridericia's Corrected QT (QTcB and QTcF) Intervals | QTcB >30 ms | 1 participants |
| 5 mg LY110140 (SD) | Change From Baseline in Bazett's and Fridericia's Corrected QT (QTcB and QTcF) Intervals | QTcF >30 ms | 1 participants |
| 5 mg LY110140 (SD) | Change From Baseline in Bazett's and Fridericia's Corrected QT (QTcB and QTcF) Intervals | QTcF >60 ms | 0 participants |
| 5 mg LY110140 (SD) | Change From Baseline in Bazett's and Fridericia's Corrected QT (QTcB and QTcF) Intervals | QTcB >60 ms | 0 participants |
| 20 mg LY110140 (SD) | Change From Baseline in Bazett's and Fridericia's Corrected QT (QTcB and QTcF) Intervals | QTcB >30 ms | 2 participants |
| 20 mg LY110140 (SD) | Change From Baseline in Bazett's and Fridericia's Corrected QT (QTcB and QTcF) Intervals | QTcF >30 ms | 0 participants |
| 20 mg LY110140 (SD) | Change From Baseline in Bazett's and Fridericia's Corrected QT (QTcB and QTcF) Intervals | QTcB >60 ms | 0 participants |
| 20 mg LY110140 (SD) | Change From Baseline in Bazett's and Fridericia's Corrected QT (QTcB and QTcF) Intervals | QTcF >60 ms | 0 participants |
| 40 mg LY110140 (SD) | Change From Baseline in Bazett's and Fridericia's Corrected QT (QTcB and QTcF) Intervals | QTcB >30 ms | 2 participants |
| 40 mg LY110140 (SD) | Change From Baseline in Bazett's and Fridericia's Corrected QT (QTcB and QTcF) Intervals | QTcF >60 ms | 0 participants |
| 40 mg LY110140 (SD) | Change From Baseline in Bazett's and Fridericia's Corrected QT (QTcB and QTcF) Intervals | QTcB >60 ms | 0 participants |
| 40 mg LY110140 (SD) | Change From Baseline in Bazett's and Fridericia's Corrected QT (QTcB and QTcF) Intervals | QTcF >30 ms | 0 participants |
| Placebo (MD) | Change From Baseline in Bazett's and Fridericia's Corrected QT (QTcB and QTcF) Intervals | QTcB >30 ms | 2 participants |
| Placebo (MD) | Change From Baseline in Bazett's and Fridericia's Corrected QT (QTcB and QTcF) Intervals | QTcF >30 ms | 0 participants |
| Placebo (MD) | Change From Baseline in Bazett's and Fridericia's Corrected QT (QTcB and QTcF) Intervals | QTcB >60 ms | 0 participants |
| Placebo (MD) | Change From Baseline in Bazett's and Fridericia's Corrected QT (QTcB and QTcF) Intervals | QTcF >60 ms | 0 participants |
| 20 mg LY110140 (MD) | Change From Baseline in Bazett's and Fridericia's Corrected QT (QTcB and QTcF) Intervals | QTcB >30 ms | 3 participants |
| 20 mg LY110140 (MD) | Change From Baseline in Bazett's and Fridericia's Corrected QT (QTcB and QTcF) Intervals | QTcF >30 ms | 1 participants |
| 20 mg LY110140 (MD) | Change From Baseline in Bazett's and Fridericia's Corrected QT (QTcB and QTcF) Intervals | QTcB >60 ms | 0 participants |
| 20 mg LY110140 (MD) | Change From Baseline in Bazett's and Fridericia's Corrected QT (QTcB and QTcF) Intervals | QTcF >60 ms | 0 participants |
| 40 mg LY110140 (MD) | Change From Baseline in Bazett's and Fridericia's Corrected QT (QTcB and QTcF) Intervals | QTcF >60 ms | 0 participants |
| 40 mg LY110140 (MD) | Change From Baseline in Bazett's and Fridericia's Corrected QT (QTcB and QTcF) Intervals | QTcF >30 ms | 4 participants |
| 40 mg LY110140 (MD) | Change From Baseline in Bazett's and Fridericia's Corrected QT (QTcB and QTcF) Intervals | QTcB >60 ms | 0 participants |
| 40 mg LY110140 (MD) | Change From Baseline in Bazett's and Fridericia's Corrected QT (QTcB and QTcF) Intervals | QTcB >30 ms | 6 participants |
Secondary
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.
Time frame: Predose up to Day 28
Population: Randomized participants, in Cohorts 4 and 5, who received at least 1 dose of study drug (excluding placebo) and had evaluable pharmacokinetic data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 5 mg LY110140 (SD) | Pharmacokinetics: Area Under the Concentration-Time Curve for Dosing Interval (Tau) at Steady State [AUC(Tau,Steady State)] of Multiple Doses (MD) of LY110140 | Fluoxetine | 1810 nanograms*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 48 |
| 5 mg LY110140 (SD) | Pharmacokinetics: Area Under the Concentration-Time Curve for Dosing Interval (Tau) at Steady State [AUC(Tau,Steady State)] of Multiple Doses (MD) of LY110140 | Norfluoxetine | 3010 nanograms*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 29 |
| 20 mg LY110140 (SD) | Pharmacokinetics: Area Under the Concentration-Time Curve for Dosing Interval (Tau) at Steady State [AUC(Tau,Steady State)] of Multiple Doses (MD) of LY110140 | Fluoxetine | 5910 nanograms*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 25 |
| 20 mg LY110140 (SD) | Pharmacokinetics: Area Under the Concentration-Time Curve for Dosing Interval (Tau) at Steady State [AUC(Tau,Steady State)] of Multiple Doses (MD) of LY110140 | Norfluoxetine | 4910 nanograms*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 19 |
Secondary
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.
Time frame: Day 1
Population: Randomized participants, in Cohorts 4 and 5, who received at least 1 dose of study drug (excluding placebo) and had evaluable pharmacokinetic data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 5 mg LY110140 (SD) | Pharmacokinetics: Area Under the Concentration-Time Curve From Zero to 24 Hours [AUC(0-24)] of Multiple Doses (MD) of LY110140 | Fluoxetine | 228 nanograms*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 29 |
| 5 mg LY110140 (SD) | Pharmacokinetics: Area Under the Concentration-Time Curve From Zero to 24 Hours [AUC(0-24)] of Multiple Doses (MD) of LY110140 | Norfluoxetine | 199 nanograms*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 41 |
| 20 mg LY110140 (SD) | Pharmacokinetics: Area Under the Concentration-Time Curve From Zero to 24 Hours [AUC(0-24)] of Multiple Doses (MD) of LY110140 | Fluoxetine | 574 nanograms*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 24 |
| 20 mg LY110140 (SD) | Pharmacokinetics: Area Under the Concentration-Time Curve From Zero to 24 Hours [AUC(0-24)] of Multiple Doses (MD) of LY110140 | Norfluoxetine | 337 nanograms*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 24 |
Secondary
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.
Time frame: Predose up to Day 43
Population: Randomized participants, in Cohorts 1, 2, and 3, who received at least 1 dose of study drug and had evaluable pharmacokinetic data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 5 mg LY110140 (SD) | Pharmacokinetics: Area Under the Concentration-Time Curve From Zero to Infinity [AUC(0-infinity)] of Single Dose (SD) of LY110140 | Fluoxetine | NA nanograms*hour per milliliter (ng*hr/mL) | — |
| 5 mg LY110140 (SD) | Pharmacokinetics: Area Under the Concentration-Time Curve From Zero to Infinity [AUC(0-infinity)] of Single Dose (SD) of LY110140 | Norfluoxetine | 407 nanograms*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 67 |
| 20 mg LY110140 (SD) | Pharmacokinetics: Area Under the Concentration-Time Curve From Zero to Infinity [AUC(0-infinity)] of Single Dose (SD) of LY110140 | Fluoxetine | 424 nanograms*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 27 |
| 20 mg LY110140 (SD) | Pharmacokinetics: Area Under the Concentration-Time Curve From Zero to Infinity [AUC(0-infinity)] of Single Dose (SD) of LY110140 | Norfluoxetine | 3360 nanograms*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 22 |
| 40 mg LY110140 (SD) | Pharmacokinetics: Area Under the Concentration-Time Curve From Zero to Infinity [AUC(0-infinity)] of Single Dose (SD) of LY110140 | Fluoxetine | 1430 nanograms*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 46 |
| 40 mg LY110140 (SD) | Pharmacokinetics: Area Under the Concentration-Time Curve From Zero to Infinity [AUC(0-infinity)] of Single Dose (SD) of LY110140 | Norfluoxetine | 6360 nanograms*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 32 |
Secondary
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.
Time frame: Predose up to Day 43
Population: Randomized participants, in Cohorts 1, 2, and 3, who received at least 1 dose of study drug and had evaluable pharmacokinetic data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 5 mg LY110140 (SD) | Pharmacokinetics: Area Under the Concentration-Time Curve From Zero to Last Time Point [AUC(0-tlast)] of Single Dose (SD) of LY110140 | Fluoxetine | NA nanograms*hour per milliliter (ng*hr/mL) | — |
| 5 mg LY110140 (SD) | Pharmacokinetics: Area Under the Concentration-Time Curve From Zero to Last Time Point [AUC(0-tlast)] of Single Dose (SD) of LY110140 | Norfluoxetine | 195 nanograms*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 74 |
| 20 mg LY110140 (SD) | Pharmacokinetics: Area Under the Concentration-Time Curve From Zero to Last Time Point [AUC(0-tlast)] of Single Dose (SD) of LY110140 | Fluoxetine | 371 nanograms*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 27 |
| 20 mg LY110140 (SD) | Pharmacokinetics: Area Under the Concentration-Time Curve From Zero to Last Time Point [AUC(0-tlast)] of Single Dose (SD) of LY110140 | Norfluoxetine | 3000 nanograms*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 20 |
| 40 mg LY110140 (SD) | Pharmacokinetics: Area Under the Concentration-Time Curve From Zero to Last Time Point [AUC(0-tlast)] of Single Dose (SD) of LY110140 | Fluoxetine | 1360 nanograms*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 46 |
| 40 mg LY110140 (SD) | Pharmacokinetics: Area Under the Concentration-Time Curve From Zero to Last Time Point [AUC(0-tlast)] of Single Dose (SD) of LY110140 | Norfluoxetine | 5850 nanograms*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 30 |
Secondary
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.
Time frame: Days 1 and 28
Population: Randomized participants, in Cohorts 4 and 5, who received at least 1 dose of study drug (excluding placebo) and had evaluable pharmacokinetic data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 5 mg LY110140 (SD) | Pharmacokinetics: Maximum Observed Drug Concentration (Cmax) of Multiple Doses (MD) of LY110140 | Day 1, Fluoxetine | 16.9 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 21 |
| 5 mg LY110140 (SD) | Pharmacokinetics: Maximum Observed Drug Concentration (Cmax) of Multiple Doses (MD) of LY110140 | Day 28, Fluoxetine | 92.9 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 43 |
| 5 mg LY110140 (SD) | Pharmacokinetics: Maximum Observed Drug Concentration (Cmax) of Multiple Doses (MD) of LY110140 | Day 1, Norfluoxetine | 10.6 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 38 |
| 5 mg LY110140 (SD) | Pharmacokinetics: Maximum Observed Drug Concentration (Cmax) of Multiple Doses (MD) of LY110140 | Day 28, Norfluoxetine | 136 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 28 |
| 20 mg LY110140 (SD) | Pharmacokinetics: Maximum Observed Drug Concentration (Cmax) of Multiple Doses (MD) of LY110140 | Day 28, Norfluoxetine | 222 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 17 |
| 20 mg LY110140 (SD) | Pharmacokinetics: Maximum Observed Drug Concentration (Cmax) of Multiple Doses (MD) of LY110140 | Day 1, Fluoxetine | 39.9 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 21 |
| 20 mg LY110140 (SD) | Pharmacokinetics: Maximum Observed Drug Concentration (Cmax) of Multiple Doses (MD) of LY110140 | Day 1, Norfluoxetine | 18.3 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 22 |
| 20 mg LY110140 (SD) | Pharmacokinetics: Maximum Observed Drug Concentration (Cmax) of Multiple Doses (MD) of LY110140 | Day 28, Fluoxetine | 284 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 24 |
Secondary
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.
Time frame: Predose up to Day 43
Population: Randomized participants, in Cohorts 1, 2, and 3, who received at least 1 dose of study drug and had evaluable pharmacokinetic data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 5 mg LY110140 (SD) | Pharmacokinetics: Maximum Observed Drug Concentration (Cmax) of Single Dose (SD) of LY110140 | Fluoxetine | NA nanograms per milliliter (ng/mL) | — |
| 5 mg LY110140 (SD) | Pharmacokinetics: Maximum Observed Drug Concentration (Cmax) of Single Dose (SD) of LY110140 | Norfluoxetine | 2.44 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 33 |
| 20 mg LY110140 (SD) | Pharmacokinetics: Maximum Observed Drug Concentration (Cmax) of Single Dose (SD) of LY110140 | Fluoxetine | 15.5 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 18 |
| 20 mg LY110140 (SD) | Pharmacokinetics: Maximum Observed Drug Concentration (Cmax) of Single Dose (SD) of LY110140 | Norfluoxetine | 13.0 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 10 |
| 40 mg LY110140 (SD) | Pharmacokinetics: Maximum Observed Drug Concentration (Cmax) of Single Dose (SD) of LY110140 | Fluoxetine | 38.7 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 17 |
| 40 mg LY110140 (SD) | Pharmacokinetics: Maximum Observed Drug Concentration (Cmax) of Single Dose (SD) of LY110140 | Norfluoxetine | 22.8 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 30 |