Trial Outcomes & Findings for A Study to Measure if There is Any Difference in How the Body Breaks Down or Inactivates Either Fluoxetine or LY2216684 When Both of These Medicines Are Given Together. (NCT NCT01243957)
NCT ID: NCT01243957
Last Updated: 2019-01-29
Results Overview
The Least Squares (LS) geometric mean AUCτ of LY2216684 was calculated based on the LY2216684 plasma concentration time curve from time 0 hour (hr) to time 24 hr (tau \[τ\]) when LY2216684 was administered alone (Day 3) and when LY2216684 was coadministered with fluoxetine (Day 27). The Day 27-to-Day 3 ratio of the LY2216684 LS geometric mean of AUCτ and the associated 90% confidence interval (CI) of the ratio were calculated.
COMPLETED
PHASE1
20 participants
Predose and 1, 2, 3, 4, 6, 8, 12, and 24 hours post-dose on Days 3 and 27
2019-01-29
Participant Flow
Participant milestones
| Measure |
LY2216684 + Fluoxetine
LY2216684: 18 milligrams (mg) oral (po) once daily (QD) on Days 1-3 and Days 25-27.
Fluoxetine: 60 mg po QD for 7 days (Days 4-10) then 20 mg po QD for 17 days (Days 11-27).
|
|---|---|
|
Overall Study
STARTED
|
20
|
|
Overall Study
COMPLETED
|
20
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
A Study to Measure if There is Any Difference in How the Body Breaks Down or Inactivates Either Fluoxetine or LY2216684 When Both of These Medicines Are Given Together.
Baseline characteristics by cohort
| Measure |
LY2216684 + Fluoxetine
n=20 Participants
LY2216684: 18 milligrams (mg) oral (po) once daily (QD) on Days 1-3 and Days 25-27.
Fluoxetine: 60 mg po QD for 7 days (Days 4-10) then 20 mg po QD for 17 days (Days 11-27).
|
|---|---|
|
Age, Continuous
|
38.3 years
STANDARD_DEVIATION 10.8 • n=5 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
16 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
2 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
18 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
5 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
15 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
20 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Predose and 1, 2, 3, 4, 6, 8, 12, and 24 hours post-dose on Days 3 and 27Population: The safety population included participants who were randomized, received study drug, and had at least 1 postdose safety assessment.
The Least Squares (LS) geometric mean AUCτ of LY2216684 was calculated based on the LY2216684 plasma concentration time curve from time 0 hour (hr) to time 24 hr (tau \[τ\]) when LY2216684 was administered alone (Day 3) and when LY2216684 was coadministered with fluoxetine (Day 27). The Day 27-to-Day 3 ratio of the LY2216684 LS geometric mean of AUCτ and the associated 90% confidence interval (CI) of the ratio were calculated.
Outcome measures
| Measure |
LY2216684 + Fluoxetine
n=20 Participants
LY2216684: 18 milligrams (mg) oral (po) once daily (QD) on Days 1-3 and Days 25-27.
Fluoxetine: 60 mg po QD for 7 days (Days 4-10) then 20 mg po QD for 17 days (Days 11-27).
|
|---|---|
|
Pharmacokinetic (PK) Parameter: Area Under the Plasma Concentration-Time Curve Over a 24-Hour Dosing Interval (AUCτ) of LY2216684
LY2216684 alone
|
677 hour*nanogram per milliliter (h*ng/mL)
Interval 609.0 to 753.0
|
|
Pharmacokinetic (PK) Parameter: Area Under the Plasma Concentration-Time Curve Over a 24-Hour Dosing Interval (AUCτ) of LY2216684
LY2216684 + fluoxetine
|
1210 hour*nanogram per milliliter (h*ng/mL)
Interval 1090.0 to 1350.0
|
PRIMARY outcome
Timeframe: Predose and 1, 2, 3, 4, 6, 8, 12, and 24 hours post-dose on Days 3 and 27Population: The safety population included participants who were randomized, received study drug, and had at least 1 postdose safety assessment.
The Least Squares (LS) geometric mean Cmax of LY2216684 was determined when LY2216684 was administered alone (Day 3) and when LY2216684 was coadministered with fluoxetine (Day 27). The Day 27-to-Day 3 ratio of the LY2216684 LS geometric mean of Cmax and the associated 90% confidence interval (CI) of the ratio were calculated.
Outcome measures
| Measure |
LY2216684 + Fluoxetine
n=20 Participants
LY2216684: 18 milligrams (mg) oral (po) once daily (QD) on Days 1-3 and Days 25-27.
Fluoxetine: 60 mg po QD for 7 days (Days 4-10) then 20 mg po QD for 17 days (Days 11-27).
|
|---|---|
|
Pharmacokinetic (PK) Parameter: Maximum Plasma Concentration (Cmax) of LY2216684
LY2216684 alone
|
55.5 nanogram per milliliter (ng/mL)
Interval 50.8 to 60.7
|
|
Pharmacokinetic (PK) Parameter: Maximum Plasma Concentration (Cmax) of LY2216684
LY2216684 + fluoxetine
|
90.6 nanogram per milliliter (ng/mL)
Interval 82.8 to 99.0
|
PRIMARY outcome
Timeframe: Predose and 1, 2, 3, 4, 6, 8, 12, and 24 hours post-dose on Days 3 and 27Population: The safety population included participants who were randomized, received study drug, and had at least 1 postdose safety assessment.
Tmax of LY2216684 was determined using the median of paired differences between the 2 treatment groups when LY2216684 was administered alone (Day 3) and when LY2216684 was coadministered with fluoxetine (Day 27). The 90% confidence interval (CI) for the median of differences was calculated.
Outcome measures
| Measure |
LY2216684 + Fluoxetine
n=20 Participants
LY2216684: 18 milligrams (mg) oral (po) once daily (QD) on Days 1-3 and Days 25-27.
Fluoxetine: 60 mg po QD for 7 days (Days 4-10) then 20 mg po QD for 17 days (Days 11-27).
|
|---|---|
|
Pharmacokinetic (PK) Parameter: Time to Maximum Plasma Concentration (Tmax) of LY2216684
LY2216684 alone
|
3.00 hours
Interval 1.0 to 6.0
|
|
Pharmacokinetic (PK) Parameter: Time to Maximum Plasma Concentration (Tmax) of LY2216684
LY2216684 + fluoxetine
|
3.00 hours
Interval 2.0 to 4.07
|
SECONDARY outcome
Timeframe: Predose and 1, 2, 3, 4, 6, 8, 12, and 24 hours post-dose on Days 24 and 27Population: The safety population included participants who were randomized, received study drug, and had at least 1 postdose safety assessment.
The Least Squares (LS) geometric means AUCτ of fluoxetine and norfluoxetine were calculated based on the fluoxetine and norfluoxetine plasma concentration time curves from time 0 hour (hr) to time 24 hr (tau \[τ\]) when fluoxetine was administered alone (Day 24) and when fluoxetine was coadministered with LY22166684 (Day 27). The Day 27-to-Day 24 ratios of fluoxetine and norfluoxetine LS geometric means of AUCτ and the associated 90% confidence interval (CI) of the ratios were calculated.
Outcome measures
| Measure |
LY2216684 + Fluoxetine
n=20 Participants
LY2216684: 18 milligrams (mg) oral (po) once daily (QD) on Days 1-3 and Days 25-27.
Fluoxetine: 60 mg po QD for 7 days (Days 4-10) then 20 mg po QD for 17 days (Days 11-27).
|
|---|---|
|
Pharmacokinetic (PK) Parameter: Area Under the Plasma Concentration Time-Curve Over a 24-Hour Dosing Interval (AUCτ) of Fluoxetine and Norfluoxetine
fluoxetine alone
|
3450 hour*nanogram per milliliter (h*ng/mL)
Interval 3060.0 to 3890.0
|
|
Pharmacokinetic (PK) Parameter: Area Under the Plasma Concentration Time-Curve Over a 24-Hour Dosing Interval (AUCτ) of Fluoxetine and Norfluoxetine
fluoxetine + LY2216684
|
3500 hour*nanogram per milliliter (h*ng/mL)
Interval 3100.0 to 3940.0
|
|
Pharmacokinetic (PK) Parameter: Area Under the Plasma Concentration Time-Curve Over a 24-Hour Dosing Interval (AUCτ) of Fluoxetine and Norfluoxetine
norfluoxetine alone
|
3170 hour*nanogram per milliliter (h*ng/mL)
Interval 2790.0 to 3590.0
|
|
Pharmacokinetic (PK) Parameter: Area Under the Plasma Concentration Time-Curve Over a 24-Hour Dosing Interval (AUCτ) of Fluoxetine and Norfluoxetine
norfluoxetine + LY2216684
|
3280 hour*nanogram per milliliter (h*ng/mL)
Interval 2890.0 to 3720.0
|
SECONDARY outcome
Timeframe: Predose and 1, 2, 3, 4, 6, 8, 12, and 24 hours post-dose on Days 24 and 27Population: The safety population included participants who were randomized, received study drug, and had at least 1 postdose safety assessment.
The Least Squares (LS) geometric means Cmax of fluoxetine and norfluoxetine were determined when fluoxetine was administered alone (Day 24) and when fluoxetine was coadministered with LY2216684 (Day 27). The Day 27-to-Day 24 ratios of fluoxetine and norfluoxetine LS geometric means of Cmax and the associated 90% confidence interval (CI) of the ratios were calculated.
Outcome measures
| Measure |
LY2216684 + Fluoxetine
n=20 Participants
LY2216684: 18 milligrams (mg) oral (po) once daily (QD) on Days 1-3 and Days 25-27.
Fluoxetine: 60 mg po QD for 7 days (Days 4-10) then 20 mg po QD for 17 days (Days 11-27).
|
|---|---|
|
Pharmacokinetic (PK) Parameter: Maximum Plasma Concentration (Cmax) of Fluoxetine and Norfluoxetine
fluoxetine alone
|
160 nanogram per milliliter (ng/mL)
Interval 142.0 to 180.0
|
|
Pharmacokinetic (PK) Parameter: Maximum Plasma Concentration (Cmax) of Fluoxetine and Norfluoxetine
fluoxetine + LY2216684
|
160 nanogram per milliliter (ng/mL)
Interval 142.0 to 180.0
|
|
Pharmacokinetic (PK) Parameter: Maximum Plasma Concentration (Cmax) of Fluoxetine and Norfluoxetine
norfluoxetine alone
|
144 nanogram per milliliter (ng/mL)
Interval 127.0 to 163.0
|
|
Pharmacokinetic (PK) Parameter: Maximum Plasma Concentration (Cmax) of Fluoxetine and Norfluoxetine
norfluoxetine + LY2216684
|
148 nanogram per milliliter (ng/mL)
Interval 131.0 to 168.0
|
SECONDARY outcome
Timeframe: Predose and 1, 2, 3, 4, 6, 8, 12, and 24 hours post-dose on Days 24 and 27Population: The safety population included participants who were randomized, received study drug, and had at least 1 postdose safety assessment.
Tmax of fluoxetine and norfluoxetine was determined using the median of paired differences between the 2 treatment groups when fluoxetine was administered alone (Day 24) and when fluoxetine was coadministered with LY2216684 (Day 27). The 90% confidence interval (CI) for the median of differences was calculated.
Outcome measures
| Measure |
LY2216684 + Fluoxetine
n=20 Participants
LY2216684: 18 milligrams (mg) oral (po) once daily (QD) on Days 1-3 and Days 25-27.
Fluoxetine: 60 mg po QD for 7 days (Days 4-10) then 20 mg po QD for 17 days (Days 11-27).
|
|---|---|
|
Pharmacokinetic (PK) Parameter: Time to Maximum Plasma Concentration (Tmax) of Fluoxetine and Norfluoxetine
fluoxetine alone
|
6.00 hours
Interval 3.0 to 12.05
|
|
Pharmacokinetic (PK) Parameter: Time to Maximum Plasma Concentration (Tmax) of Fluoxetine and Norfluoxetine
fluoxetine + LY2216684
|
6.00 hours
Interval 0.0 to 12.0
|
|
Pharmacokinetic (PK) Parameter: Time to Maximum Plasma Concentration (Tmax) of Fluoxetine and Norfluoxetine
norfluoxetine alone
|
12.00 hours
Interval 0.0 to 24.0
|
|
Pharmacokinetic (PK) Parameter: Time to Maximum Plasma Concentration (Tmax) of Fluoxetine and Norfluoxetine
norfluoxetine + LY2216684
|
4.00 hours
Interval 0.0 to 12.0
|
Adverse Events
LY2216684
Fluoxetine
LY2216684 + Fluoxetine
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
LY2216684
n=20 participants at risk
LY2216684: 18 milligrams (mg) oral (po) once daily (QD) on Days 1-3 and Days 25-27.
|
Fluoxetine
n=20 participants at risk
Fluoxetine: 60 mg po QD for 7 days (Days 4-10) then 20 mg po QD for 17 days (Days 11-27).
|
LY2216684 + Fluoxetine
n=20 participants at risk
LY2216684: 18 milligrams (mg) oral (po) once daily (QD) on Days 1-3 and Days 25-27.
Fluoxetine: 60 mg po QD for 7 days (Days 4-10) then 20 mg po QD for 17 days (Days 11-27).
|
|---|---|---|---|
|
Cardiac disorders
Palpitations
|
0.00%
0/20
|
0.00%
0/20
|
10.0%
2/20 • Number of events 2
|
|
Cardiac disorders
Tachycardia
|
10.0%
2/20 • Number of events 2
|
0.00%
0/20
|
10.0%
2/20 • Number of events 2
|
|
Ear and labyrinth disorders
Ear pain
|
0.00%
0/20
|
5.0%
1/20 • Number of events 1
|
0.00%
0/20
|
|
Ear and labyrinth disorders
Vertigo
|
0.00%
0/20
|
5.0%
1/20 • Number of events 1
|
5.0%
1/20 • Number of events 1
|
|
Eye disorders
Dry eye
|
0.00%
0/20
|
5.0%
1/20 • Number of events 1
|
0.00%
0/20
|
|
Eye disorders
Vision blurred
|
0.00%
0/20
|
15.0%
3/20 • Number of events 3
|
0.00%
0/20
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/20
|
5.0%
1/20 • Number of events 1
|
5.0%
1/20 • Number of events 1
|
|
Gastrointestinal disorders
Defaecation urgency
|
5.0%
1/20 • Number of events 1
|
0.00%
0/20
|
5.0%
1/20 • Number of events 1
|
|
Gastrointestinal disorders
Dry mouth
|
5.0%
1/20 • Number of events 1
|
5.0%
1/20 • Number of events 1
|
10.0%
2/20 • Number of events 2
|
|
Gastrointestinal disorders
Nausea
|
40.0%
8/20 • Number of events 8
|
20.0%
4/20 • Number of events 5
|
50.0%
10/20 • Number of events 10
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/20
|
0.00%
0/20
|
10.0%
2/20 • Number of events 2
|
|
General disorders
Asthenia
|
0.00%
0/20
|
0.00%
0/20
|
5.0%
1/20 • Number of events 1
|
|
General disorders
Catheter site inflammation
|
5.0%
1/20 • Number of events 1
|
0.00%
0/20
|
0.00%
0/20
|
|
General disorders
Chills
|
15.0%
3/20 • Number of events 3
|
0.00%
0/20
|
25.0%
5/20 • Number of events 5
|
|
General disorders
Face oedema
|
0.00%
0/20
|
5.0%
1/20 • Number of events 1
|
0.00%
0/20
|
|
General disorders
Feeling cold
|
0.00%
0/20
|
0.00%
0/20
|
5.0%
1/20 • Number of events 1
|
|
General disorders
Feeling hot
|
5.0%
1/20 • Number of events 1
|
5.0%
1/20 • Number of events 1
|
5.0%
1/20 • Number of events 1
|
|
General disorders
Feeling jittery
|
0.00%
0/20
|
0.00%
0/20
|
5.0%
1/20 • Number of events 1
|
|
Infections and infestations
Herpes simplex
|
0.00%
0/20
|
5.0%
1/20 • Number of events 1
|
5.0%
1/20 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/20
|
5.0%
1/20 • Number of events 1
|
0.00%
0/20
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
0.00%
0/20
|
5.0%
1/20 • Number of events 1
|
5.0%
1/20 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
0.00%
0/20
|
5.0%
1/20 • Number of events 1
|
0.00%
0/20
|
|
Nervous system disorders
Dizziness
|
20.0%
4/20 • Number of events 4
|
10.0%
2/20 • Number of events 2
|
10.0%
2/20 • Number of events 4
|
|
Nervous system disorders
Headache
|
5.0%
1/20 • Number of events 1
|
40.0%
8/20 • Number of events 12
|
20.0%
4/20 • Number of events 5
|
|
Nervous system disorders
Paraesthesia
|
20.0%
4/20 • Number of events 4
|
0.00%
0/20
|
15.0%
3/20 • Number of events 3
|
|
Nervous system disorders
Presyncope
|
0.00%
0/20
|
5.0%
1/20 • Number of events 1
|
0.00%
0/20
|
|
Nervous system disorders
Somnolence
|
0.00%
0/20
|
10.0%
2/20 • Number of events 2
|
5.0%
1/20 • Number of events 1
|
|
Nervous system disorders
Tremor
|
0.00%
0/20
|
0.00%
0/20
|
10.0%
2/20 • Number of events 2
|
|
Psychiatric disorders
Euphoric mood
|
10.0%
2/20 • Number of events 2
|
0.00%
0/20
|
0.00%
0/20
|
|
Psychiatric disorders
Insomnia
|
0.00%
0/20
|
10.0%
2/20 • Number of events 2
|
10.0%
2/20 • Number of events 2
|
|
Renal and urinary disorders
Micturition urgency
|
5.0%
1/20 • Number of events 1
|
0.00%
0/20
|
5.0%
1/20 • Number of events 1
|
|
Renal and urinary disorders
Pollakiuria
|
5.0%
1/20 • Number of events 1
|
0.00%
0/20
|
0.00%
0/20
|
|
Renal and urinary disorders
Urinary hesitation
|
10.0%
2/20 • Number of events 2
|
0.00%
0/20
|
5.0%
1/20 • Number of events 1
|
|
Reproductive system and breast disorders
Dysmenorrhoea
|
0.00%
0/20
|
5.0%
1/20 • Number of events 1
|
0.00%
0/20
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/20
|
5.0%
1/20 • Number of events 1
|
0.00%
0/20
|
|
Respiratory, thoracic and mediastinal disorders
Throat irritation
|
0.00%
0/20
|
5.0%
1/20 • Number of events 1
|
0.00%
0/20
|
|
Skin and subcutaneous tissue disorders
Dermal cyst
|
0.00%
0/20
|
5.0%
1/20 • Number of events 1
|
0.00%
0/20
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
0.00%
0/20
|
5.0%
1/20 • Number of events 1
|
0.00%
0/20
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
0.00%
0/20
|
0.00%
0/20
|
10.0%
2/20 • Number of events 2
|
|
Vascular disorders
Hot flush
|
5.0%
1/20 • Number of events 1
|
5.0%
1/20 • Number of events 1
|
15.0%
3/20 • Number of events 3
|
|
Vascular disorders
Orthostatic hypotension
|
0.00%
0/20
|
5.0%
1/20 • Number of events 1
|
0.00%
0/20
|
Additional Information
Chief Medical Officer
Eli Lilly and Company
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60