Trial Outcomes & Findings for A Study of LY110140 in Healthy Japanese Male Participants (NCT NCT01569126)
NCT ID: NCT01569126
Last Updated: 2014-02-10
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
56 participants
Primary outcome timeframe
Baseline up to Day 43
Results posted on
2014-02-10
Participant Flow
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).
Participant milestones
| Measure |
5 mg LY110140 (SD)
Cohort 1: 5-milligram (mg) LY110140 (fluoxetine hydrochloride) capsule orally administered once, in a fasted state, during the SD period.
|
20 mg LY110140 (SD)
Cohort 2: 20-mg LY110140 (fluoxetine hydrochloride) capsule orally administered once, in a fasted state, during the SD period.
|
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.
|
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.
|
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.
|
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.
|
|---|---|---|---|---|---|---|
|
Overall Study
STARTED
|
8
|
8
|
8
|
8
|
12
|
12
|
|
Overall Study
Received at Least 1 Dose of Study Drug
|
8
|
8
|
8
|
8
|
12
|
12
|
|
Overall Study
COMPLETED
|
8
|
8
|
8
|
8
|
12
|
12
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
A Study of LY110140 in Healthy Japanese Male Participants
Baseline characteristics by cohort
| Measure |
5 mg LY110140 (SD)
n=8 Participants
Cohort 1: 5-milligram (mg) LY110140 (fluoxetine hydrochloride) capsule orally administered once, in a fasted state, during the SD period.
|
20 mg LY110140 (SD)
n=8 Participants
Cohort 2: 20-mg LY110140 (fluoxetine hydrochloride) capsule orally administered once, in a fasted state, during the SD period.
|
40 mg LY110140 (SD)
n=8 Participants
Cohort 3: 40-mg LY110140 (fluoxetine hydrochloride) dose (two 20-mg LY110140 capsules) orally administered once, in a fasted state, during the SD period.
|
Placebo (MD)
n=8 Participants
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.
|
20 mg LY110140 (MD)
n=12 Participants
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.
|
40 mg LY110140 (MD)
n=12 Participants
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.
|
Total
n=56 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|---|
|
Age, Continuous
|
27.1 years
STANDARD_DEVIATION 4.4 • n=99 Participants
|
25.8 years
STANDARD_DEVIATION 2.4 • n=107 Participants
|
24.6 years
STANDARD_DEVIATION 2.4 • n=206 Participants
|
27.1 years
STANDARD_DEVIATION 4.4 • n=7 Participants
|
25.8 years
STANDARD_DEVIATION 6.3 • n=31 Participants
|
28.7 years
STANDARD_DEVIATION 6.2 • n=30 Participants
|
26.6 years
STANDARD_DEVIATION 4.9 • n=3 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=31 Participants
|
0 Participants
n=30 Participants
|
0 Participants
n=3 Participants
|
|
Sex: Female, Male
Male
|
8 Participants
n=99 Participants
|
8 Participants
n=107 Participants
|
8 Participants
n=206 Participants
|
8 Participants
n=7 Participants
|
12 Participants
n=31 Participants
|
12 Participants
n=30 Participants
|
56 Participants
n=3 Participants
|
|
Race/Ethnicity, Customized
Japanese
|
8 participants
n=99 Participants
|
8 participants
n=107 Participants
|
8 participants
n=206 Participants
|
8 participants
n=7 Participants
|
12 participants
n=31 Participants
|
12 participants
n=30 Participants
|
56 participants
n=3 Participants
|
|
Region of Enrollment
Japan
|
8 participants
n=99 Participants
|
8 participants
n=107 Participants
|
8 participants
n=206 Participants
|
8 participants
n=7 Participants
|
12 participants
n=31 Participants
|
12 participants
n=30 Participants
|
56 participants
n=3 Participants
|
|
Cytochrome P450 2D6 (CYP2D6) intermediate and extensive metabolizers
CYP2D6 extensive metabolizers
|
4 participants
n=99 Participants
|
4 participants
n=107 Participants
|
4 participants
n=206 Participants
|
4 participants
n=7 Participants
|
6 participants
n=31 Participants
|
6 participants
n=30 Participants
|
28 participants
n=3 Participants
|
|
Cytochrome P450 2D6 (CYP2D6) intermediate and extensive metabolizers
CYP2D6 intermediate metabolizers
|
4 participants
n=99 Participants
|
4 participants
n=107 Participants
|
4 participants
n=206 Participants
|
4 participants
n=7 Participants
|
6 participants
n=31 Participants
|
6 participants
n=30 Participants
|
28 participants
n=3 Participants
|
PRIMARY outcome
Timeframe: Baseline up to Day 43Population: 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.
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.
Outcome measures
| Measure |
5 mg LY110140 (SD)
n=8 Participants
Cohort 1: 5-milligram (mg) LY110140 (fluoxetine hydrochloride) capsule orally administered once, in a fasted state, during the SD period.
|
20 mg LY110140 (SD)
n=8 Participants
Cohort 2: 20-mg LY110140 (fluoxetine hydrochloride) capsule orally administered once, in a fasted state, during the SD period.
|
40 mg LY110140 (SD)
n=8 Participants
Cohort 3: 40-mg LY110140 (fluoxetine hydrochloride) dose (two 20-mg LY110140 capsules) orally administered once, in a fasted state, during the SD period.
|
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.
|
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.
|
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.
|
|---|---|---|---|---|---|---|
|
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
|
0 participants
|
0 participants
|
—
|
—
|
—
|
|
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
|
0 participants
|
0 participants
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline up to Day 70Population: 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.
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.
Outcome measures
| Measure |
5 mg LY110140 (SD)
n=8 Participants
Cohort 1: 5-milligram (mg) LY110140 (fluoxetine hydrochloride) capsule orally administered once, in a fasted state, during the SD period.
|
20 mg LY110140 (SD)
n=12 Participants
Cohort 2: 20-mg LY110140 (fluoxetine hydrochloride) capsule orally administered once, in a fasted state, during the SD period.
|
40 mg LY110140 (SD)
n=12 Participants
Cohort 3: 40-mg LY110140 (fluoxetine hydrochloride) dose (two 20-mg LY110140 capsules) orally administered once, in a fasted state, during the SD period.
|
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.
|
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.
|
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.
|
|---|---|---|---|---|---|---|
|
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
|
0 participants
|
2 participants
|
—
|
—
|
—
|
|
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
|
0 participants
|
0 participants
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose up to Day 43Population: Randomized participants, in Cohorts 1, 2, and 3, who received at least 1 dose of study drug and had evaluable pharmacokinetic data.
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.
Outcome measures
| Measure |
5 mg LY110140 (SD)
n=8 Participants
Cohort 1: 5-milligram (mg) LY110140 (fluoxetine hydrochloride) capsule orally administered once, in a fasted state, during the SD period.
|
20 mg LY110140 (SD)
n=8 Participants
Cohort 2: 20-mg LY110140 (fluoxetine hydrochloride) capsule orally administered once, in a fasted state, during the SD period.
|
40 mg LY110140 (SD)
n=8 Participants
Cohort 3: 40-mg LY110140 (fluoxetine hydrochloride) dose (two 20-mg LY110140 capsules) orally administered once, in a fasted state, during the SD period.
|
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.
|
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.
|
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.
|
|---|---|---|---|---|---|---|
|
Pharmacokinetics: Maximum Observed Drug Concentration (Cmax) of Single Dose (SD) of LY110140
Fluoxetine
|
NA nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation NA
The fluoxetine concentrations following a single administration of 5 mg LY110140 were below the quantifiable lower limit.
|
15.5 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 18
|
38.7 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 17
|
—
|
—
|
—
|
|
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
|
13.0 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 10
|
22.8 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 30
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose up to Day 43Population: Randomized participants, in Cohorts 1, 2, and 3, who received at least 1 dose of study drug and had evaluable pharmacokinetic data.
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.
Outcome measures
| Measure |
5 mg LY110140 (SD)
n=8 Participants
Cohort 1: 5-milligram (mg) LY110140 (fluoxetine hydrochloride) capsule orally administered once, in a fasted state, during the SD period.
|
20 mg LY110140 (SD)
n=8 Participants
Cohort 2: 20-mg LY110140 (fluoxetine hydrochloride) capsule orally administered once, in a fasted state, during the SD period.
|
40 mg LY110140 (SD)
n=8 Participants
Cohort 3: 40-mg LY110140 (fluoxetine hydrochloride) dose (two 20-mg LY110140 capsules) orally administered once, in a fasted state, during the SD period.
|
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.
|
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.
|
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.
|
|---|---|---|---|---|---|---|
|
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)
Geometric Coefficient of Variation NA
The fluoxetine concentrations following a single administration of 5 mg LY110140 were below the quantifiable lower limit.
|
371 nanograms*hour per milliliter (ng*hr/mL)
Geometric Coefficient of Variation 27
|
1360 nanograms*hour per milliliter (ng*hr/mL)
Geometric Coefficient of Variation 46
|
—
|
—
|
—
|
|
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
|
3000 nanograms*hour per milliliter (ng*hr/mL)
Geometric Coefficient of Variation 20
|
5850 nanograms*hour per milliliter (ng*hr/mL)
Geometric Coefficient of Variation 30
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose up to Day 43Population: Randomized participants, in Cohorts 1, 2, and 3, who received at least 1 dose of study drug and had evaluable pharmacokinetic data.
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.
Outcome measures
| Measure |
5 mg LY110140 (SD)
n=8 Participants
Cohort 1: 5-milligram (mg) LY110140 (fluoxetine hydrochloride) capsule orally administered once, in a fasted state, during the SD period.
|
20 mg LY110140 (SD)
n=8 Participants
Cohort 2: 20-mg LY110140 (fluoxetine hydrochloride) capsule orally administered once, in a fasted state, during the SD period.
|
40 mg LY110140 (SD)
n=8 Participants
Cohort 3: 40-mg LY110140 (fluoxetine hydrochloride) dose (two 20-mg LY110140 capsules) orally administered once, in a fasted state, during the SD period.
|
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.
|
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.
|
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.
|
|---|---|---|---|---|---|---|
|
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)
Geometric Coefficient of Variation NA
The fluoxetine concentrations following a single administration of 5 mg LY110140 were below the quantifiable lower limit.
|
424 nanograms*hour per milliliter (ng*hr/mL)
Geometric Coefficient of Variation 27
|
1430 nanograms*hour per milliliter (ng*hr/mL)
Geometric Coefficient of Variation 46
|
—
|
—
|
—
|
|
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
|
3360 nanograms*hour per milliliter (ng*hr/mL)
Geometric Coefficient of Variation 22
|
6360 nanograms*hour per milliliter (ng*hr/mL)
Geometric Coefficient of Variation 32
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Days 1 and 28Population: Randomized participants, in Cohorts 4 and 5, who received at least 1 dose of study drug (excluding placebo) and had evaluable pharmacokinetic data.
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.
Outcome measures
| Measure |
5 mg LY110140 (SD)
n=12 Participants
Cohort 1: 5-milligram (mg) LY110140 (fluoxetine hydrochloride) capsule orally administered once, in a fasted state, during the SD period.
|
20 mg LY110140 (SD)
n=12 Participants
Cohort 2: 20-mg LY110140 (fluoxetine hydrochloride) capsule orally administered once, in a fasted state, during the SD period.
|
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.
|
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.
|
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.
|
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.
|
|---|---|---|---|---|---|---|
|
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
|
39.9 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 21
|
—
|
—
|
—
|
—
|
|
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
|
284 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 24
|
—
|
—
|
—
|
—
|
|
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
|
18.3 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 22
|
—
|
—
|
—
|
—
|
|
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
|
222 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 17
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1Population: Randomized participants, in Cohorts 4 and 5, who received at least 1 dose of study drug (excluding placebo) and had evaluable pharmacokinetic data.
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.
Outcome measures
| Measure |
5 mg LY110140 (SD)
n=12 Participants
Cohort 1: 5-milligram (mg) LY110140 (fluoxetine hydrochloride) capsule orally administered once, in a fasted state, during the SD period.
|
20 mg LY110140 (SD)
n=12 Participants
Cohort 2: 20-mg LY110140 (fluoxetine hydrochloride) capsule orally administered once, in a fasted state, during the SD period.
|
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.
|
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.
|
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.
|
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.
|
|---|---|---|---|---|---|---|
|
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
|
574 nanograms*hour per milliliter (ng*hr/mL)
Geometric Coefficient of Variation 24
|
—
|
—
|
—
|
—
|
|
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
|
337 nanograms*hour per milliliter (ng*hr/mL)
Geometric Coefficient of Variation 24
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Predose up to Day 28Population: Randomized participants, in Cohorts 4 and 5, who received at least 1 dose of study drug (excluding placebo) and had evaluable pharmacokinetic data.
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.
Outcome measures
| Measure |
5 mg LY110140 (SD)
n=12 Participants
Cohort 1: 5-milligram (mg) LY110140 (fluoxetine hydrochloride) capsule orally administered once, in a fasted state, during the SD period.
|
20 mg LY110140 (SD)
n=12 Participants
Cohort 2: 20-mg LY110140 (fluoxetine hydrochloride) capsule orally administered once, in a fasted state, during the SD period.
|
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.
|
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.
|
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.
|
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.
|
|---|---|---|---|---|---|---|
|
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
|
5910 nanograms*hour per milliliter (ng*hr/mL)
Geometric Coefficient of Variation 25
|
—
|
—
|
—
|
—
|
|
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
|
4910 nanograms*hour per milliliter (ng*hr/mL)
Geometric Coefficient of Variation 19
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
5 mg LY110140 (SD)
n=8 Participants
Cohort 1: 5-milligram (mg) LY110140 (fluoxetine hydrochloride) capsule orally administered once, in a fasted state, during the SD period.
|
20 mg LY110140 (SD)
n=8 Participants
Cohort 2: 20-mg LY110140 (fluoxetine hydrochloride) capsule orally administered once, in a fasted state, during the SD period.
|
40 mg LY110140 (SD)
n=8 Participants
Cohort 3: 40-mg LY110140 (fluoxetine hydrochloride) dose (two 20-mg LY110140 capsules) orally administered once, in a fasted state, during the SD period.
|
Placebo (MD)
n=8 Participants
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.
|
20 mg LY110140 (MD)
n=12 Participants
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.
|
40 mg LY110140 (MD)
n=12 Participants
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.
|
|---|---|---|---|---|---|---|
|
Change From Baseline in Bazett's and Fridericia's Corrected QT (QTcB and QTcF) Intervals
QTcF >60 ms
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Change From Baseline in Bazett's and Fridericia's Corrected QT (QTcB and QTcF) Intervals
QTcB >30 ms
|
1 participants
|
2 participants
|
2 participants
|
2 participants
|
3 participants
|
6 participants
|
|
Change From Baseline in Bazett's and Fridericia's Corrected QT (QTcB and QTcF) Intervals
QTcF >30 ms
|
1 participants
|
0 participants
|
0 participants
|
0 participants
|
1 participants
|
4 participants
|
|
Change From Baseline in Bazett's and Fridericia's Corrected QT (QTcB and QTcF) Intervals
QTcB >60 ms
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
Adverse Events
5 mg LY110140 (SD)
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
20 mg LY110140 (SD)
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
40 mg LY110140 (SD)
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Placebo (MD)
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
20 mg LY110140 (MD)
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
40 mg LY110140 (MD)
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
5 mg LY110140 (SD)
n=8 participants at risk
Cohort 1: 5-milligram (mg) LY110140 (fluoxetine hydrochloride) capsule orally administered once, in a fasted state, during the SD period.
|
20 mg LY110140 (SD)
n=8 participants at risk
Cohort 2: 20-mg LY110140 (fluoxetine hydrochloride) capsule orally administered once, in a fasted state, during the SD period.
|
40 mg LY110140 (SD)
n=8 participants at risk
Cohort 3: 40-mg LY110140 (fluoxetine hydrochloride) dose (two 20-mg LY110140 capsules) orally administered once, in a fasted state, during the SD period.
|
Placebo (MD)
n=8 participants at risk
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.
|
20 mg LY110140 (MD)
n=12 participants at risk
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.
|
40 mg LY110140 (MD)
n=12 participants at risk
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.
|
|---|---|---|---|---|---|---|
|
Cardiac disorders
Atrioventricular block first degree
|
12.5%
1/8 • Number of events 2
|
0.00%
0/8
|
0.00%
0/8
|
0.00%
0/8
|
0.00%
0/12
|
16.7%
2/12 • Number of events 2
|
|
Eye disorders
Conjunctivitis allergic
|
0.00%
0/8
|
0.00%
0/8
|
0.00%
0/8
|
0.00%
0/8
|
0.00%
0/12
|
8.3%
1/12 • Number of events 1
|
|
Eye disorders
Eye discharge
|
0.00%
0/8
|
0.00%
0/8
|
0.00%
0/8
|
12.5%
1/8 • Number of events 1
|
0.00%
0/12
|
0.00%
0/12
|
|
Eye disorders
Ocular hyperaemia
|
0.00%
0/8
|
0.00%
0/8
|
0.00%
0/8
|
12.5%
1/8 • Number of events 1
|
0.00%
0/12
|
0.00%
0/12
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/8
|
0.00%
0/8
|
0.00%
0/8
|
0.00%
0/8
|
8.3%
1/12 • Number of events 1
|
0.00%
0/12
|
|
Gastrointestinal disorders
Haemorrhoids
|
0.00%
0/8
|
0.00%
0/8
|
0.00%
0/8
|
0.00%
0/8
|
0.00%
0/12
|
8.3%
1/12 • Number of events 1
|
|
Gastrointestinal disorders
Proctalgia
|
0.00%
0/8
|
0.00%
0/8
|
0.00%
0/8
|
0.00%
0/8
|
0.00%
0/12
|
8.3%
1/12 • Number of events 1
|
|
Gastrointestinal disorders
Stomatitis
|
0.00%
0/8
|
0.00%
0/8
|
0.00%
0/8
|
0.00%
0/8
|
8.3%
1/12 • Number of events 1
|
0.00%
0/12
|
|
General disorders
Chills
|
12.5%
1/8 • Number of events 1
|
0.00%
0/8
|
0.00%
0/8
|
0.00%
0/8
|
0.00%
0/12
|
0.00%
0/12
|
|
General disorders
Pyrexia
|
0.00%
0/8
|
0.00%
0/8
|
0.00%
0/8
|
25.0%
2/8 • Number of events 2
|
8.3%
1/12 • Number of events 1
|
0.00%
0/12
|
|
Infections and infestations
Tonsillitis
|
0.00%
0/8
|
0.00%
0/8
|
0.00%
0/8
|
12.5%
1/8 • Number of events 1
|
0.00%
0/12
|
0.00%
0/12
|
|
Injury, poisoning and procedural complications
Excoriation
|
0.00%
0/8
|
0.00%
0/8
|
0.00%
0/8
|
0.00%
0/8
|
0.00%
0/12
|
8.3%
1/12 • Number of events 1
|
|
Investigations
Alanine aminotransferase increased
|
0.00%
0/8
|
0.00%
0/8
|
0.00%
0/8
|
0.00%
0/8
|
16.7%
2/12 • Number of events 3
|
8.3%
1/12 • Number of events 1
|
|
Investigations
Aspartate aminotransferase increased
|
0.00%
0/8
|
0.00%
0/8
|
0.00%
0/8
|
0.00%
0/8
|
8.3%
1/12 • Number of events 1
|
8.3%
1/12 • Number of events 1
|
|
Investigations
Blood triglycerides increased
|
0.00%
0/8
|
12.5%
1/8 • Number of events 1
|
0.00%
0/8
|
0.00%
0/8
|
0.00%
0/12
|
8.3%
1/12 • Number of events 1
|
|
Investigations
White blood cell count decreased
|
0.00%
0/8
|
0.00%
0/8
|
25.0%
2/8 • Number of events 3
|
0.00%
0/8
|
0.00%
0/12
|
8.3%
1/12 • Number of events 1
|
|
Investigations
White blood cell count increased
|
12.5%
1/8 • Number of events 1
|
0.00%
0/8
|
0.00%
0/8
|
0.00%
0/8
|
0.00%
0/12
|
8.3%
1/12 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
12.5%
1/8 • Number of events 1
|
0.00%
0/8
|
0.00%
0/8
|
0.00%
0/8
|
0.00%
0/12
|
0.00%
0/12
|
|
Nervous system disorders
Dizziness
|
0.00%
0/8
|
0.00%
0/8
|
0.00%
0/8
|
0.00%
0/8
|
0.00%
0/12
|
8.3%
1/12 • Number of events 1
|
|
Nervous system disorders
Headache
|
0.00%
0/8
|
0.00%
0/8
|
0.00%
0/8
|
37.5%
3/8 • Number of events 3
|
0.00%
0/12
|
0.00%
0/12
|
|
Psychiatric disorders
Anxiety
|
0.00%
0/8
|
0.00%
0/8
|
0.00%
0/8
|
0.00%
0/8
|
0.00%
0/12
|
8.3%
1/12 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/8
|
0.00%
0/8
|
0.00%
0/8
|
12.5%
1/8 • Number of events 1
|
0.00%
0/12
|
0.00%
0/12
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
0.00%
0/8
|
0.00%
0/8
|
0.00%
0/8
|
25.0%
2/8 • Number of events 2
|
0.00%
0/12
|
0.00%
0/12
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
0.00%
0/8
|
0.00%
0/8
|
0.00%
0/8
|
12.5%
1/8 • Number of events 1
|
0.00%
0/12
|
0.00%
0/12
|
Additional Information
Chief Medical Officer
Eli Lilly and Company
Phone: 800-545-5979
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60