Trial Outcomes & Findings for A Study of LY2216684 and Theophylline in Healthy Subjects (NCT NCT01263106)
NCT ID: NCT01263106
Last Updated: 2019-07-08
Results Overview
The Least Squares (LS) geometric mean was based on AUC0-∞. The AUC for theophylline was calculated on Day 1 of a given period when theophylline was administered alone and on Day 3 of another period when theophylline was coadministered with LY2216684.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
21 participants
Primary outcome timeframe
Predose 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post-administration of theophylline on Days 1 and 3
Results posted on
2019-07-08
Participant Flow
Participant milestones
| Measure |
Theophylline Alone, Then LY2216684 + Theophylline
Period 1: single 200 mg theophylline oral dose on Day 1; Washout period of at least 7 days; Period 2: 18 mg LY2216684 orally once daily on Days 1-5. Single dose of 200 mg theophylline coadministered on Day 3.
|
LY2216684 + Theophylline, Then Theophylline Alone
Period 1: 18 mg LY2216684 orally once daily on Days 1-5. Single dose of 200 mg theophylline coadministered on Day 3.Washout period of at least 7 days; Period 2: single 200 mg theophylline oral dose on Day 1
|
|---|---|---|
|
Period 1 (7 Days)
STARTED
|
11
|
10
|
|
Period 1 (7 Days)
COMPLETED
|
11
|
10
|
|
Period 1 (7 Days)
NOT COMPLETED
|
0
|
0
|
|
Washout (at Least 7 Days)
STARTED
|
11
|
10
|
|
Washout (at Least 7 Days)
COMPLETED
|
10
|
9
|
|
Washout (at Least 7 Days)
NOT COMPLETED
|
1
|
1
|
|
Period 2 (7 Days)
STARTED
|
10
|
9
|
|
Period 2 (7 Days)
COMPLETED
|
10
|
9
|
|
Period 2 (7 Days)
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
| Measure |
Theophylline Alone, Then LY2216684 + Theophylline
Period 1: single 200 mg theophylline oral dose on Day 1; Washout period of at least 7 days; Period 2: 18 mg LY2216684 orally once daily on Days 1-5. Single dose of 200 mg theophylline coadministered on Day 3.
|
LY2216684 + Theophylline, Then Theophylline Alone
Period 1: 18 mg LY2216684 orally once daily on Days 1-5. Single dose of 200 mg theophylline coadministered on Day 3.Washout period of at least 7 days; Period 2: single 200 mg theophylline oral dose on Day 1
|
|---|---|---|
|
Washout (at Least 7 Days)
Lost to Follow-up
|
1
|
1
|
Baseline Characteristics
A Study of LY2216684 and Theophylline in Healthy Subjects
Baseline characteristics by cohort
| Measure |
All Participants
n=21 Participants
All started participants.
|
|---|---|
|
Age, Continuous
|
33.2 years
STANDARD_DEVIATION 6.9 • n=5 Participants
|
|
Sex: Female, Male
Female
|
9 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
12 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
12 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
9 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
|
7 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
14 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
|
21 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Predose 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post-administration of theophylline on Days 1 and 3Population: The safety population included participants who were randomized, received study drug, and had at least 1 post-dose safety assessment.
The Least Squares (LS) geometric mean was based on AUC0-∞. The AUC for theophylline was calculated on Day 1 of a given period when theophylline was administered alone and on Day 3 of another period when theophylline was coadministered with LY2216684.
Outcome measures
| Measure |
Theophylline Alone
n=20 Participants
Single 200 mg theophylline oral dose on Day 1.
|
LY2216684 + Theophylline
n=20 Participants
Oral dose of 18 mg LY2216684, once daily on Days 1-5 with single 200 mg theophylline dose coadministered on Day 3.
|
|---|---|---|
|
Pharmacokinetics: Area Under the Plasma Concentration-Time Curve From Time 0 Hour to Infinity (AUC0-∞) of Theophylline
|
70200 nanogram*hour per milliliter (ng*h/mL)
Interval 62300.0 to 79200.0
|
78700 nanogram*hour per milliliter (ng*h/mL)
Interval 69800.0 to 88800.0
|
PRIMARY outcome
Timeframe: Predose 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post-administration of theophylline on Days 1 and 3Population: The safety population included participants who were randomized, received study drug, and had at least 1 post-dose safety assessment.
The Least Squares (LS) geometric mean was based on Cmax for theophylline on Day 1 of a given period when theophylline was administered alone and on Day 3 of another period when theophylline was coadministered with LY2216684.
Outcome measures
| Measure |
Theophylline Alone
n=20 Participants
Single 200 mg theophylline oral dose on Day 1.
|
LY2216684 + Theophylline
n=20 Participants
Oral dose of 18 mg LY2216684, once daily on Days 1-5 with single 200 mg theophylline dose coadministered on Day 3.
|
|---|---|---|
|
Pharmacokinetics: Maximum Plasma Concentration (Cmax) of Theophylline
|
3174.35 nanogram per milliliter (ng/mL)
Interval 2796.84 to 3602.81
|
3054.84 nanogram per milliliter (ng/mL)
Interval 2691.79 to 3466.97
|
PRIMARY outcome
Timeframe: Predose 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post-administration of theophylline on Days 1 and 3Population: The safety population included participants who were randomized, received study drug, and had at least 1 post-dose safety assessment.
This outcome was measured based on Tmax for theophylline on Day 1 of a given period when theophylline was administered alone and on Day 3 of another period when theophylline was coadministered with LY2216684.
Outcome measures
| Measure |
Theophylline Alone
n=19 Participants
Single 200 mg theophylline oral dose on Day 1.
|
LY2216684 + Theophylline
n=19 Participants
Oral dose of 18 mg LY2216684, once daily on Days 1-5 with single 200 mg theophylline dose coadministered on Day 3.
|
|---|---|---|
|
Pharmacokinetics: Time to Maximum Plasma Concentration (Tmax) of Theophylline
|
12.00 hour (h)
Interval 4.0 to 12.03
|
12.00 hour (h)
Interval 3.0 to 12.0
|
SECONDARY outcome
Timeframe: Baseline, Day 1Population: The safety population included participants who were randomized, received study drug, and had at least 1 post-dose safety assessment.
Outcome measures
| Measure |
Theophylline Alone
n=20 Participants
Single 200 mg theophylline oral dose on Day 1.
|
LY2216684 + Theophylline
Oral dose of 18 mg LY2216684, once daily on Days 1-5 with single 200 mg theophylline dose coadministered on Day 3.
|
|---|---|---|
|
Mean Change From Baseline in Heart Rate: 200 mg Theophylline
Day 1 (-2 to 0 hours)
|
74.1 beats per minute (bpm)
Standard Deviation 8.9
|
—
|
|
Mean Change From Baseline in Heart Rate: 200 mg Theophylline
Day 1 (23 to 24 hours)
|
82.7 beats per minute (bpm)
Standard Deviation 9.5
|
—
|
SECONDARY outcome
Timeframe: Baseline, Day 1, Day 3Population: The safety population included participants who were randomized, received study drug, and had at least 1 post-dose safety assessment.
Outcome measures
| Measure |
Theophylline Alone
n=20 Participants
Single 200 mg theophylline oral dose on Day 1.
|
LY2216684 + Theophylline
Oral dose of 18 mg LY2216684, once daily on Days 1-5 with single 200 mg theophylline dose coadministered on Day 3.
|
|---|---|---|
|
Mean Change From Baseline in Heart Rate: 18 mg LY221684 + 200 mg Theophylline
Day 1 (-2 to 0 hr)
|
70.1 beats per minute (bpm)
Standard Deviation 7.2
|
—
|
|
Mean Change From Baseline in Heart Rate: 18 mg LY221684 + 200 mg Theophylline
Day 1 (23 to 24 hr)
|
89.6 beats per minute (bpm)
Standard Deviation 9.1
|
—
|
|
Mean Change From Baseline in Heart Rate: 18 mg LY221684 + 200 mg Theophylline
Day 3 (-2 to 0 hr)
|
74.1 beats per minute (bpm)
Standard Deviation 8.9
|
—
|
|
Mean Change From Baseline in Heart Rate: 18 mg LY221684 + 200 mg Theophylline
Day 3 (23 to 24 hr)
|
95.7 beats per minute (bpm)
Standard Deviation 10.7
|
—
|
Adverse Events
LY2216684
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Theophylline
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
LY2216684 + Theophylline
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
LY2216684
n=20 participants at risk
18 mg LY2216684 orally
|
Theophylline
n=20 participants at risk
single 200-mg theophylline oral dose
|
LY2216684 + Theophylline
n=20 participants at risk
18 mg LY2216684 orally with single 200-mg theophylline oral dose coadministered
|
|---|---|---|---|
|
Cardiac disorders
Palpitations
|
10.0%
2/20 • Number of events 2
During Period 1: 1 participant took theophylline alone but was not given LY + theophylline and 1 participant took LY + theophylline but was not given theophylline alone.
|
0.00%
0/20
During Period 1: 1 participant took theophylline alone but was not given LY + theophylline and 1 participant took LY + theophylline but was not given theophylline alone.
|
5.0%
1/20 • Number of events 1
During Period 1: 1 participant took theophylline alone but was not given LY + theophylline and 1 participant took LY + theophylline but was not given theophylline alone.
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/20
During Period 1: 1 participant took theophylline alone but was not given LY + theophylline and 1 participant took LY + theophylline but was not given theophylline alone.
|
5.0%
1/20 • Number of events 1
During Period 1: 1 participant took theophylline alone but was not given LY + theophylline and 1 participant took LY + theophylline but was not given theophylline alone.
|
0.00%
0/20
During Period 1: 1 participant took theophylline alone but was not given LY + theophylline and 1 participant took LY + theophylline but was not given theophylline alone.
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
5.0%
1/20 • Number of events 1
During Period 1: 1 participant took theophylline alone but was not given LY + theophylline and 1 participant took LY + theophylline but was not given theophylline alone.
|
0.00%
0/20
During Period 1: 1 participant took theophylline alone but was not given LY + theophylline and 1 participant took LY + theophylline but was not given theophylline alone.
|
0.00%
0/20
During Period 1: 1 participant took theophylline alone but was not given LY + theophylline and 1 participant took LY + theophylline but was not given theophylline alone.
|
|
Gastrointestinal disorders
Nausea
|
15.0%
3/20 • Number of events 3
During Period 1: 1 participant took theophylline alone but was not given LY + theophylline and 1 participant took LY + theophylline but was not given theophylline alone.
|
0.00%
0/20
During Period 1: 1 participant took theophylline alone but was not given LY + theophylline and 1 participant took LY + theophylline but was not given theophylline alone.
|
0.00%
0/20
During Period 1: 1 participant took theophylline alone but was not given LY + theophylline and 1 participant took LY + theophylline but was not given theophylline alone.
|
|
Gastrointestinal disorders
Vomiting
|
15.0%
3/20 • Number of events 3
During Period 1: 1 participant took theophylline alone but was not given LY + theophylline and 1 participant took LY + theophylline but was not given theophylline alone.
|
0.00%
0/20
During Period 1: 1 participant took theophylline alone but was not given LY + theophylline and 1 participant took LY + theophylline but was not given theophylline alone.
|
0.00%
0/20
During Period 1: 1 participant took theophylline alone but was not given LY + theophylline and 1 participant took LY + theophylline but was not given theophylline alone.
|
|
General disorders
Chills
|
5.0%
1/20 • Number of events 1
During Period 1: 1 participant took theophylline alone but was not given LY + theophylline and 1 participant took LY + theophylline but was not given theophylline alone.
|
0.00%
0/20
During Period 1: 1 participant took theophylline alone but was not given LY + theophylline and 1 participant took LY + theophylline but was not given theophylline alone.
|
5.0%
1/20 • Number of events 1
During Period 1: 1 participant took theophylline alone but was not given LY + theophylline and 1 participant took LY + theophylline but was not given theophylline alone.
|
|
General disorders
Feeling jittery
|
5.0%
1/20 • Number of events 1
During Period 1: 1 participant took theophylline alone but was not given LY + theophylline and 1 participant took LY + theophylline but was not given theophylline alone.
|
0.00%
0/20
During Period 1: 1 participant took theophylline alone but was not given LY + theophylline and 1 participant took LY + theophylline but was not given theophylline alone.
|
5.0%
1/20 • Number of events 1
During Period 1: 1 participant took theophylline alone but was not given LY + theophylline and 1 participant took LY + theophylline but was not given theophylline alone.
|
|
General disorders
Thirst
|
0.00%
0/20
During Period 1: 1 participant took theophylline alone but was not given LY + theophylline and 1 participant took LY + theophylline but was not given theophylline alone.
|
0.00%
0/20
During Period 1: 1 participant took theophylline alone but was not given LY + theophylline and 1 participant took LY + theophylline but was not given theophylline alone.
|
5.0%
1/20 • Number of events 1
During Period 1: 1 participant took theophylline alone but was not given LY + theophylline and 1 participant took LY + theophylline but was not given theophylline alone.
|
|
General disorders
Vessel puncture site pain
|
0.00%
0/20
During Period 1: 1 participant took theophylline alone but was not given LY + theophylline and 1 participant took LY + theophylline but was not given theophylline alone.
|
0.00%
0/20
During Period 1: 1 participant took theophylline alone but was not given LY + theophylline and 1 participant took LY + theophylline but was not given theophylline alone.
|
5.0%
1/20 • Number of events 1
During Period 1: 1 participant took theophylline alone but was not given LY + theophylline and 1 participant took LY + theophylline but was not given theophylline alone.
|
|
Infections and infestations
Pharyngitis
|
0.00%
0/20
During Period 1: 1 participant took theophylline alone but was not given LY + theophylline and 1 participant took LY + theophylline but was not given theophylline alone.
|
10.0%
2/20 • Number of events 2
During Period 1: 1 participant took theophylline alone but was not given LY + theophylline and 1 participant took LY + theophylline but was not given theophylline alone.
|
0.00%
0/20
During Period 1: 1 participant took theophylline alone but was not given LY + theophylline and 1 participant took LY + theophylline but was not given theophylline alone.
|
|
Nervous system disorders
Dizziness
|
15.0%
3/20 • Number of events 3
During Period 1: 1 participant took theophylline alone but was not given LY + theophylline and 1 participant took LY + theophylline but was not given theophylline alone.
|
0.00%
0/20
During Period 1: 1 participant took theophylline alone but was not given LY + theophylline and 1 participant took LY + theophylline but was not given theophylline alone.
|
10.0%
2/20 • Number of events 2
During Period 1: 1 participant took theophylline alone but was not given LY + theophylline and 1 participant took LY + theophylline but was not given theophylline alone.
|
|
Nervous system disorders
Headache
|
5.0%
1/20 • Number of events 1
During Period 1: 1 participant took theophylline alone but was not given LY + theophylline and 1 participant took LY + theophylline but was not given theophylline alone.
|
5.0%
1/20 • Number of events 1
During Period 1: 1 participant took theophylline alone but was not given LY + theophylline and 1 participant took LY + theophylline but was not given theophylline alone.
|
10.0%
2/20 • Number of events 2
During Period 1: 1 participant took theophylline alone but was not given LY + theophylline and 1 participant took LY + theophylline but was not given theophylline alone.
|
|
Nervous system disorders
Paraesthesia
|
5.0%
1/20 • Number of events 1
During Period 1: 1 participant took theophylline alone but was not given LY + theophylline and 1 participant took LY + theophylline but was not given theophylline alone.
|
0.00%
0/20
During Period 1: 1 participant took theophylline alone but was not given LY + theophylline and 1 participant took LY + theophylline but was not given theophylline alone.
|
0.00%
0/20
During Period 1: 1 participant took theophylline alone but was not given LY + theophylline and 1 participant took LY + theophylline but was not given theophylline alone.
|
|
Nervous system disorders
Somnolence
|
5.0%
1/20 • Number of events 1
During Period 1: 1 participant took theophylline alone but was not given LY + theophylline and 1 participant took LY + theophylline but was not given theophylline alone.
|
0.00%
0/20
During Period 1: 1 participant took theophylline alone but was not given LY + theophylline and 1 participant took LY + theophylline but was not given theophylline alone.
|
0.00%
0/20
During Period 1: 1 participant took theophylline alone but was not given LY + theophylline and 1 participant took LY + theophylline but was not given theophylline alone.
|
|
Psychiatric disorders
Anxiety
|
0.00%
0/20
During Period 1: 1 participant took theophylline alone but was not given LY + theophylline and 1 participant took LY + theophylline but was not given theophylline alone.
|
0.00%
0/20
During Period 1: 1 participant took theophylline alone but was not given LY + theophylline and 1 participant took LY + theophylline but was not given theophylline alone.
|
5.0%
1/20 • Number of events 1
During Period 1: 1 participant took theophylline alone but was not given LY + theophylline and 1 participant took LY + theophylline but was not given theophylline alone.
|
|
Reproductive system and breast disorders
Dysmenorrhoea
|
0.00%
0/20
During Period 1: 1 participant took theophylline alone but was not given LY + theophylline and 1 participant took LY + theophylline but was not given theophylline alone.
|
5.0%
1/20 • Number of events 1
During Period 1: 1 participant took theophylline alone but was not given LY + theophylline and 1 participant took LY + theophylline but was not given theophylline alone.
|
5.0%
1/20 • Number of events 1
During Period 1: 1 participant took theophylline alone but was not given LY + theophylline and 1 participant took LY + theophylline but was not given theophylline alone.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/20
During Period 1: 1 participant took theophylline alone but was not given LY + theophylline and 1 participant took LY + theophylline but was not given theophylline alone.
|
0.00%
0/20
During Period 1: 1 participant took theophylline alone but was not given LY + theophylline and 1 participant took LY + theophylline but was not given theophylline alone.
|
5.0%
1/20 • Number of events 1
During Period 1: 1 participant took theophylline alone but was not given LY + theophylline and 1 participant took LY + theophylline but was not given theophylline alone.
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.00%
0/20
During Period 1: 1 participant took theophylline alone but was not given LY + theophylline and 1 participant took LY + theophylline but was not given theophylline alone.
|
5.0%
1/20 • Number of events 1
During Period 1: 1 participant took theophylline alone but was not given LY + theophylline and 1 participant took LY + theophylline but was not given theophylline alone.
|
0.00%
0/20
During Period 1: 1 participant took theophylline alone but was not given LY + theophylline and 1 participant took LY + theophylline but was not given theophylline alone.
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
0.00%
0/20
During Period 1: 1 participant took theophylline alone but was not given LY + theophylline and 1 participant took LY + theophylline but was not given theophylline alone.
|
5.0%
1/20 • Number of events 1
During Period 1: 1 participant took theophylline alone but was not given LY + theophylline and 1 participant took LY + theophylline but was not given theophylline alone.
|
0.00%
0/20
During Period 1: 1 participant took theophylline alone but was not given LY + theophylline and 1 participant took LY + theophylline but was not given theophylline alone.
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/20
During Period 1: 1 participant took theophylline alone but was not given LY + theophylline and 1 participant took LY + theophylline but was not given theophylline alone.
|
0.00%
0/20
During Period 1: 1 participant took theophylline alone but was not given LY + theophylline and 1 participant took LY + theophylline but was not given theophylline alone.
|
5.0%
1/20 • Number of events 1
During Period 1: 1 participant took theophylline alone but was not given LY + theophylline and 1 participant took LY + theophylline but was not given theophylline alone.
|
|
Skin and subcutaneous tissue disorders
Rash papular
|
0.00%
0/20
During Period 1: 1 participant took theophylline alone but was not given LY + theophylline and 1 participant took LY + theophylline but was not given theophylline alone.
|
0.00%
0/20
During Period 1: 1 participant took theophylline alone but was not given LY + theophylline and 1 participant took LY + theophylline but was not given theophylline alone.
|
5.0%
1/20 • Number of events 1
During Period 1: 1 participant took theophylline alone but was not given LY + theophylline and 1 participant took LY + theophylline but was not given theophylline alone.
|
|
Vascular disorders
Flushing
|
0.00%
0/20
During Period 1: 1 participant took theophylline alone but was not given LY + theophylline and 1 participant took LY + theophylline but was not given theophylline alone.
|
0.00%
0/20
During Period 1: 1 participant took theophylline alone but was not given LY + theophylline and 1 participant took LY + theophylline but was not given theophylline alone.
|
5.0%
1/20 • Number of events 1
During Period 1: 1 participant took theophylline alone but was not given LY + theophylline and 1 participant took LY + theophylline but was not given theophylline alone.
|
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