Trial Outcomes & Findings for A Pharmacokinetic Study of the Coadministration of LY2216684 With Sertraline (NCT NCT01250873)
NCT ID: NCT01250873
Last Updated: 2019-01-04
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 LY221684 was administered alone (Day 3) and when LY2216684 was coadministered with sertraline (Day 13). The Day 13-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
0, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose on Day 3 and Day 13
2019-01-04
Participant Flow
Participant milestones
| Measure |
LY2216684/Sertraline/LY2216684 + Sertraline
Period 1: LY2216684 18 milligram (mg) oral (po) dose on Days 1-3; Period 2: Sertraline 50 mg po dose on Day 4 followed by sertraline 100 mg po dose on Days 5-10; Period 3: LY2216684 18 mg po dose + sertraline 100 mg po dose on Days 11-13.
|
|---|---|
|
Period 1: LY2216684 (Days 1-3)
STARTED
|
20
|
|
Period 1: LY2216684 (Days 1-3)
COMPLETED
|
18
|
|
Period 1: LY2216684 (Days 1-3)
NOT COMPLETED
|
2
|
|
Period 2: Sertraline (Day 4, 5-10)
STARTED
|
18
|
|
Period 2: Sertraline (Day 4, 5-10)
COMPLETED
|
18
|
|
Period 2: Sertraline (Day 4, 5-10)
NOT COMPLETED
|
0
|
|
Period 3:LY2216684+Sertraline(Days11-13)
STARTED
|
18
|
|
Period 3:LY2216684+Sertraline(Days11-13)
COMPLETED
|
17
|
|
Period 3:LY2216684+Sertraline(Days11-13)
NOT COMPLETED
|
1
|
Reasons for withdrawal
| Measure |
LY2216684/Sertraline/LY2216684 + Sertraline
Period 1: LY2216684 18 milligram (mg) oral (po) dose on Days 1-3; Period 2: Sertraline 50 mg po dose on Day 4 followed by sertraline 100 mg po dose on Days 5-10; Period 3: LY2216684 18 mg po dose + sertraline 100 mg po dose on Days 11-13.
|
|---|---|
|
Period 1: LY2216684 (Days 1-3)
Adverse Event
|
2
|
|
Period 3:LY2216684+Sertraline(Days11-13)
Adverse Event
|
1
|
Baseline Characteristics
A Pharmacokinetic Study of the Coadministration of LY2216684 With Sertraline
Baseline characteristics by cohort
| Measure |
LY2216684/Sertraline/LY2216684 + Sertraline
n=20 Participants
Period 1: LY2216684 18 milligram (mg) oral (po) dose on Days 1-3; Period 2: Sertraline 50 mg po dose on Day 4 followed by sertraline 100 mg po dose on Days 5-10; Period 3: LY2216684 18 mg po dose + sertraline 100 mg po dose on Days 11-13.
|
|---|---|
|
Age, Continuous
|
37.8 years
STANDARD_DEVIATION 8.8 • n=5 Participants
|
|
Sex: Female, Male
Female
|
9 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
11 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
12 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
8 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
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
13 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
4 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: 0, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose on Day 3 and Day 13Population: 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 LY221684 was administered alone (Day 3) and when LY2216684 was coadministered with sertraline (Day 13). The Day 13-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/Sertraline/LY2216684 + Sertraline
n=18 Participants
Period 1: LY2216684 18 milligram (mg) oral (po) dose on Days 1-3; Period 2: Sertraline 50 mg po dose on Day 4 followed by sertraline 100 mg po dose on Days 5-10; Period 3: LY2216684 18 mg po dose + sertraline 100 mg po dose on Days 11-13.
|
|---|---|
|
Pharmacokinetic (PK) Parameter: Area Under the Plasma Concentration-Time Curve Over a 24-Hour Dosing Interval (AUCτ) of LY2216684
LY2216684 alone
|
675 hour*nanogram per milliliter (h*ng/mL)
Interval 618.0 to 738.0
|
|
Pharmacokinetic (PK) Parameter: Area Under the Plasma Concentration-Time Curve Over a 24-Hour Dosing Interval (AUCτ) of LY2216684
LY2216684 + sertraline
|
792 hour*nanogram per milliliter (h*ng/mL)
Interval 716.0 to 876.0
|
PRIMARY outcome
Timeframe: 0, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose on Day 3 and Day 13Population: 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 sertraline (Day 13). The Day 13-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/Sertraline/LY2216684 + Sertraline
n=18 Participants
Period 1: LY2216684 18 milligram (mg) oral (po) dose on Days 1-3; Period 2: Sertraline 50 mg po dose on Day 4 followed by sertraline 100 mg po dose on Days 5-10; Period 3: LY2216684 18 mg po dose + sertraline 100 mg po dose on Days 11-13.
|
|---|---|
|
Pharmacokinetic (PK) Parameter: Maximum Plasma Concentration (Cmax) of LY2216684
LY2216684 alone
|
65.9 nanogram per milliliter (ng/mL)
Interval 60.9 to 71.4
|
|
Pharmacokinetic (PK) Parameter: Maximum Plasma Concentration (Cmax) of LY2216684
LY2216684 + sertraline
|
74.9 nanogram per milliliter (ng/mL)
Interval 68.1 to 82.4
|
PRIMARY outcome
Timeframe: 0, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose on Day 3 and Day 13Population: 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 sertraline (Day 13). The 90% confidence interval (CI) for the median of differences was calculated.
Outcome measures
| Measure |
LY2216684/Sertraline/LY2216684 + Sertraline
n=13 Participants
Period 1: LY2216684 18 milligram (mg) oral (po) dose on Days 1-3; Period 2: Sertraline 50 mg po dose on Day 4 followed by sertraline 100 mg po dose on Days 5-10; Period 3: LY2216684 18 mg po dose + sertraline 100 mg po dose on Days 11-13.
|
|---|---|
|
Pharmacokinetic (PK) Parameter: Time to Maximum Plasma Concentration (Tmax) of LY2216684
LY2216684 alone
|
2.00 hours
Interval 2.0 to 4.0
|
|
Pharmacokinetic (PK) Parameter: Time to Maximum Plasma Concentration (Tmax) of LY2216684
LY2216684 + sertraline
|
3.00 hours
Interval 2.0 to 4.0
|
PRIMARY outcome
Timeframe: 0, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose on Day 10 and Day 13Population: 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 sertraline was calculated based on the sertraline plasma concentration time curve from time 0 hour (hr) to time 24 hr (tau \[τ\]) when sertraline was administered alone (Day 10) and when sertraline was coadministered with LY2216684 (Day 13). The Day 13-to-Day 10 ratio of the sertraline LS geometric mean of AUCτ and the associated 90% confidence interval (CI) of the ratio were calculated.
Outcome measures
| Measure |
LY2216684/Sertraline/LY2216684 + Sertraline
n=17 Participants
Period 1: LY2216684 18 milligram (mg) oral (po) dose on Days 1-3; Period 2: Sertraline 50 mg po dose on Day 4 followed by sertraline 100 mg po dose on Days 5-10; Period 3: LY2216684 18 mg po dose + sertraline 100 mg po dose on Days 11-13.
|
|---|---|
|
Pharmacokinetic (PK) Parameter: Area Under the Plasma Concentration-Time Curve Over a 24-Hour Dosing Interval (AUCτ) of Sertraline
sertraline alone
|
1240 hour*nanogram per milliliter (h*ng/mL)
Interval 1090.0 to 1400.0
|
|
Pharmacokinetic (PK) Parameter: Area Under the Plasma Concentration-Time Curve Over a 24-Hour Dosing Interval (AUCτ) of Sertraline
sertraline + LY2216684
|
1570 hour*nanogram per milliliter (h*ng/mL)
Interval 1380.0 to 1790.0
|
PRIMARY outcome
Timeframe: 0, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose on Day 10 and Day 13Population: 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 sertraline was determined when sertraline was administered alone (Day 10) and when sertraline was coadministered with LY2216684 (Day 13). The Day 13-to-Day 10 ratio of the sertraline LS geometric mean of Cmax and the associated 90% confidence interval (CI) of the ratio were calculated.
Outcome measures
| Measure |
LY2216684/Sertraline/LY2216684 + Sertraline
n=17 Participants
Period 1: LY2216684 18 milligram (mg) oral (po) dose on Days 1-3; Period 2: Sertraline 50 mg po dose on Day 4 followed by sertraline 100 mg po dose on Days 5-10; Period 3: LY2216684 18 mg po dose + sertraline 100 mg po dose on Days 11-13.
|
|---|---|
|
Pharmacokinetic (PK) Parameter: Maximum Plasma Concentration (Cmax) of Sertraline
sertraline alone
|
70.7 nanogram per milliliter (ng/mL)
Interval 62.4 to 80.1
|
|
Pharmacokinetic (PK) Parameter: Maximum Plasma Concentration (Cmax) of Sertraline
sertraline + LY2216684
|
86.4 nanogram per milliliter (ng/mL)
Interval 75.6 to 98.7
|
PRIMARY outcome
Timeframe: 0, 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose on Day 10 and Day 13Population: The safety population included participants who were randomized, received study drug, and had at least 1 postdose safety assessment.
Tmax of sertraline was determined using the median of paired differences between the 2 treatment groups when sertraline was administered alone (Day 10) and when sertraline was coadministered with LY2216684 (Day 13). The 90% confidence interval (CI) for the median of differences was calculated.
Outcome measures
| Measure |
LY2216684/Sertraline/LY2216684 + Sertraline
n=13 Participants
Period 1: LY2216684 18 milligram (mg) oral (po) dose on Days 1-3; Period 2: Sertraline 50 mg po dose on Day 4 followed by sertraline 100 mg po dose on Days 5-10; Period 3: LY2216684 18 mg po dose + sertraline 100 mg po dose on Days 11-13.
|
|---|---|
|
Pharmacokinetic (PK) Parameter: Time to Maximum Plasma Concentration (Tmax) of Sertraline
sertraline alone
|
6.00 hours
Interval 2.0 to 12.0
|
|
Pharmacokinetic (PK) Parameter: Time to Maximum Plasma Concentration (Tmax) of Sertraline
sertraline + LY2216684
|
8.00 hours
Interval 6.0 to 8.0
|
Adverse Events
LY2216684
Sertraline
LY2216684 + Sertraline
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
LY2216684
n=20 participants at risk
Period 1: LY2216684 18 milligram (mg) oral (po) dose on Days 1-3; Period 2: Sertraline 50 mg po dose on Day 4 followed by sertraline 100 mg po dose on Days 5-10; Period 3: LY2216684 18 mg po dose + sertraline 100 mg po dose on Days 11-13.
|
Sertraline
n=18 participants at risk
Period 2: Sertraline 50 mg po dose on Day 4 followed by sertraline 100 mg po dose on Days 5-10.
|
LY2216684 + Sertraline
n=18 participants at risk
Period 3: LY2216684 18 mg po dose + sertraline 100 mg po dose on Days 11-13.
|
|---|---|---|---|
|
Ear and labyrinth disorders
Vertigo
|
5.0%
1/20 • Number of events 1
|
0.00%
0/18
|
5.6%
1/18 • Number of events 1
|
|
Eye disorders
Dry eye
|
5.0%
1/20 • Number of events 1
|
0.00%
0/18
|
0.00%
0/18
|
|
Gastrointestinal disorders
Abdominal pain
|
5.0%
1/20 • Number of events 1
|
0.00%
0/18
|
0.00%
0/18
|
|
Gastrointestinal disorders
Constipation
|
15.0%
3/20 • Number of events 3
|
0.00%
0/18
|
0.00%
0/18
|
|
Gastrointestinal disorders
Diarrhoea haemorrhagic
|
5.0%
1/20 • Number of events 1
|
0.00%
0/18
|
0.00%
0/18
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/20
|
0.00%
0/18
|
5.6%
1/18 • Number of events 1
|
|
Gastrointestinal disorders
Flatulence
|
5.0%
1/20 • Number of events 1
|
0.00%
0/18
|
0.00%
0/18
|
|
Gastrointestinal disorders
Nausea
|
10.0%
2/20 • Number of events 2
|
0.00%
0/18
|
16.7%
3/18 • Number of events 3
|
|
Gastrointestinal disorders
Vomiting
|
5.0%
1/20 • Number of events 1
|
0.00%
0/18
|
5.6%
1/18 • Number of events 1
|
|
General disorders
Chills
|
5.0%
1/20 • Number of events 1
|
0.00%
0/18
|
0.00%
0/18
|
|
General disorders
Feeling of body temperature change
|
30.0%
6/20 • Number of events 7
|
0.00%
0/18
|
5.6%
1/18 • Number of events 1
|
|
General disorders
Irritability
|
0.00%
0/20
|
0.00%
0/18
|
5.6%
1/18 • Number of events 1
|
|
General disorders
Pain
|
5.0%
1/20 • Number of events 1
|
0.00%
0/18
|
0.00%
0/18
|
|
Infections and infestations
Cellulitis
|
0.00%
0/20
|
5.6%
1/18 • Number of events 1
|
0.00%
0/18
|
|
Infections and infestations
Herpes zoster
|
5.0%
1/20 • Number of events 1
|
0.00%
0/18
|
0.00%
0/18
|
|
Infections and infestations
Lower respiratory tract infection
|
0.00%
0/20
|
0.00%
0/18
|
5.6%
1/18 • Number of events 1
|
|
Infections and infestations
Pharyngitis
|
0.00%
0/20
|
0.00%
0/18
|
5.6%
1/18 • Number of events 1
|
|
Infections and infestations
Rhinitis
|
5.0%
1/20 • Number of events 1
|
0.00%
0/18
|
0.00%
0/18
|
|
Infections and infestations
Sinusitis
|
5.0%
1/20 • Number of events 1
|
5.6%
1/18 • Number of events 1
|
0.00%
0/18
|
|
Metabolism and nutrition disorders
Hyperphagia
|
5.0%
1/20 • Number of events 1
|
0.00%
0/18
|
0.00%
0/18
|
|
Musculoskeletal and connective tissue disorders
Costochondritis
|
5.0%
1/20 • Number of events 1
|
0.00%
0/18
|
0.00%
0/18
|
|
Musculoskeletal and connective tissue disorders
Groin pain
|
5.0%
1/20 • Number of events 1
|
0.00%
0/18
|
0.00%
0/18
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
0.00%
0/20
|
0.00%
0/18
|
5.6%
1/18 • Number of events 1
|
|
Nervous system disorders
Disturbance in attention
|
0.00%
0/20
|
0.00%
0/18
|
5.6%
1/18 • Number of events 1
|
|
Nervous system disorders
Dizziness
|
0.00%
0/20
|
0.00%
0/18
|
11.1%
2/18 • Number of events 2
|
|
Nervous system disorders
Headache
|
10.0%
2/20 • Number of events 2
|
16.7%
3/18 • Number of events 4
|
11.1%
2/18 • Number of events 2
|
|
Nervous system disorders
Presyncope
|
0.00%
0/20
|
5.6%
1/18 • Number of events 1
|
0.00%
0/18
|
|
Nervous system disorders
Somnolence
|
5.0%
1/20 • Number of events 1
|
0.00%
0/18
|
11.1%
2/18 • Number of events 2
|
|
Psychiatric disorders
Anxiety
|
5.0%
1/20 • Number of events 1
|
0.00%
0/18
|
5.6%
1/18 • Number of events 1
|
|
Psychiatric disorders
Insomnia
|
5.0%
1/20 • Number of events 1
|
0.00%
0/18
|
5.6%
1/18 • Number of events 1
|
|
Renal and urinary disorders
Dysuria
|
10.0%
2/20 • Number of events 2
|
0.00%
0/18
|
0.00%
0/18
|
|
Renal and urinary disorders
Semenuria
|
10.0%
2/20 • Number of events 2
|
5.6%
1/18 • Number of events 1
|
5.6%
1/18 • Number of events 1
|
|
Renal and urinary disorders
Urinary retention
|
0.00%
0/20
|
0.00%
0/18
|
5.6%
1/18 • Number of events 1
|
|
Reproductive system and breast disorders
Testicular pain
|
0.00%
0/20
|
0.00%
0/18
|
5.6%
1/18 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/20
|
5.6%
1/18 • Number of events 1
|
5.6%
1/18 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
5.0%
1/20 • Number of events 1
|
0.00%
0/18
|
0.00%
0/18
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
0.00%
0/20
|
0.00%
0/18
|
5.6%
1/18 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
5.0%
1/20 • Number of events 1
|
0.00%
0/18
|
0.00%
0/18
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
5.0%
1/20 • Number of events 1
|
0.00%
0/18
|
0.00%
0/18
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/20
|
0.00%
0/18
|
11.1%
2/18 • Number of events 2
|
|
Vascular disorders
Flushing
|
5.0%
1/20 • Number of events 1
|
0.00%
0/18
|
0.00%
0/18
|
|
Vascular disorders
Vasodilatation
|
5.0%
1/20 • Number of events 1
|
0.00%
0/18
|
0.00%
0/18
|
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