Trial Outcomes & Findings for A Study of LY2216684 and Digoxin in Healthy Subjects (NCT NCT01266590)
NCT ID: NCT01266590
Last Updated: 2018-10-22
Results Overview
Cmax of digoxin when administered alone and when co-administered with LY2216684.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
30 participants
Primary outcome timeframe
Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours post-dose on Days 7 and 14
Results posted on
2018-10-22
Participant Flow
Participant milestones
| Measure |
LY2216684 + Digoxin
Two oral 0.5-milligrams (mg) (two 0.25-mg tablets) doses of digoxin separated by 12 hours on Day 1, followed by once daily 0.25-mg (single 0.25-mg tablet) dose of digoxin on Days 2-14. Daily oral 18-mg (two 9-mg tablets) doses of LY2216684 on Days 8-14.
|
|---|---|
|
Overall Study
STARTED
|
30
|
|
Overall Study
COMPLETED
|
24
|
|
Overall Study
NOT COMPLETED
|
6
|
Reasons for withdrawal
| Measure |
LY2216684 + Digoxin
Two oral 0.5-milligrams (mg) (two 0.25-mg tablets) doses of digoxin separated by 12 hours on Day 1, followed by once daily 0.25-mg (single 0.25-mg tablet) dose of digoxin on Days 2-14. Daily oral 18-mg (two 9-mg tablets) doses of LY2216684 on Days 8-14.
|
|---|---|
|
Overall Study
Adverse Event
|
3
|
|
Overall Study
Lost to Follow-up
|
1
|
|
Overall Study
Withdrawal by Subject
|
1
|
|
Overall Study
Physician Decision
|
1
|
Baseline Characteristics
A Study of LY2216684 and Digoxin in Healthy Subjects
Baseline characteristics by cohort
| Measure |
LY2216684 + Digoxin
n=30 Participants
Two oral 0.5-milligrams (mg) (two 0.25-mg tablets) doses of digoxin separated by 12 hours on Day 1, followed by once daily 0.25-mg (single 0.25-mg tablet) dose of digoxin on Days 2-14. Daily oral 18-mg (two 9-mg tablets) doses of LY2216684 on Days 8-14.
|
|---|---|
|
Age, Continuous
|
34.9 years
STANDARD_DEVIATION 10.8 • n=5 Participants
|
|
Sex: Female, Male
Female
|
12 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
18 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
19 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
11 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
|
23 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
30 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours post-dose on Days 7 and 14Population: All participants who received at least 1 dose of study drug and had evaluable Cmax values.
Cmax of digoxin when administered alone and when co-administered with LY2216684.
Outcome measures
| Measure |
Digoxin
n=27 Participants
0.5-milligrams (mg) (two 0.25-mg tablets) digoxin administered orally twice on Day 1 and 0.25-mg (single 0.25-mg tablet) digoxin administered orally once daily on Days 2 through 7.
|
LY2216684 + Digoxin
n=25 Participants
0.25-mg (single 0.25-mg tablet) digoxin and 18-mg (two 9-mg tablets) LY2216684 administered orally once daily on Days 8 through 14.
|
|---|---|---|
|
Pharmacokinetics of Digoxin: Maximum Plasma Concentration (Cmax)
|
1.433 nanograms/milliliter (ng/mL)
Interval 1.266 to 1.622
|
1.424 nanograms/milliliter (ng/mL)
Interval 1.254 to 1.617
|
PRIMARY outcome
Timeframe: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours post-dose on Days 7 and 14Population: All participants who received at least 1 dose of study drug and had evaluable Tmax values.
Tmax of digoxin when administered alone and when co-administered with LY2216684.
Outcome measures
| Measure |
Digoxin
n=25 Participants
0.5-milligrams (mg) (two 0.25-mg tablets) digoxin administered orally twice on Day 1 and 0.25-mg (single 0.25-mg tablet) digoxin administered orally once daily on Days 2 through 7.
|
LY2216684 + Digoxin
n=25 Participants
0.25-mg (single 0.25-mg tablet) digoxin and 18-mg (two 9-mg tablets) LY2216684 administered orally once daily on Days 8 through 14.
|
|---|---|---|
|
Pharmacokinetics of Digoxin: Time to Maximum Plasma Concentration (Tmax)
|
2.00 hours
Interval 0.5 to 3.0
|
1.00 hours
Interval 0.5 to 4.0
|
PRIMARY outcome
Timeframe: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours post-dose on Days 7 and 14Population: All participants who received at least 1 dose of study drug and evaluable AUCt values.
AUCt at steady state of digoxin when administered alone and when co-administered with LY2216684.
Outcome measures
| Measure |
Digoxin
n=27 Participants
0.5-milligrams (mg) (two 0.25-mg tablets) digoxin administered orally twice on Day 1 and 0.25-mg (single 0.25-mg tablet) digoxin administered orally once daily on Days 2 through 7.
|
LY2216684 + Digoxin
n=25 Participants
0.25-mg (single 0.25-mg tablet) digoxin and 18-mg (two 9-mg tablets) LY2216684 administered orally once daily on Days 8 through 14.
|
|---|---|---|
|
Pharmacokinetics of Digoxin: Area Under the Concentration Time Curve at Steady State Over the Dosing Interval (AUCt)
|
14.6 hours*nanograms/milliliter (h*ng/mL)
Interval 13.2 to 16.1
|
14.3 hours*nanograms/milliliter (h*ng/mL)
Interval 12.9 to 15.8
|
Adverse Events
Digoxin 0.5mg
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Digoxin 0.25mg
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
LY2216684 + Digoxin
Serious events: 0 serious events
Other events: 16 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Digoxin 0.5mg
n=30 participants at risk
0.5-milligrams (mg) (two 0.25-mg tablets) digoxin administered orally twice on Day 1.
|
Digoxin 0.25mg
n=28 participants at risk
0.25-mg (single 0.25-mg tablet) digoxin administered orally once daily on Days 2 through 7.
|
LY2216684 + Digoxin
n=27 participants at risk
0.25-mg (single 0.25-mg tablet) digoxin and 18-mg (two 9-mg tablets) LY2216684 administered orally once daily on Days 8 through 14.
|
|---|---|---|---|
|
Eye disorders
Xerophthalmia
|
0.00%
0/30
|
0.00%
0/28
|
3.7%
1/27 • Number of events 1
|
|
Gastrointestinal disorders
Abdominal distension
|
0.00%
0/30
|
0.00%
0/28
|
3.7%
1/27 • Number of events 1
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/30
|
7.1%
2/28 • Number of events 2
|
3.7%
1/27 • Number of events 1
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/30
|
0.00%
0/28
|
3.7%
1/27 • Number of events 1
|
|
Gastrointestinal disorders
Dry mouth
|
0.00%
0/30
|
0.00%
0/28
|
3.7%
1/27 • Number of events 2
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/30
|
0.00%
0/28
|
18.5%
5/27 • Number of events 5
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/30
|
0.00%
0/28
|
3.7%
1/27 • Number of events 1
|
|
General disorders
Application site irritation
|
3.3%
1/30 • Number of events 1
|
0.00%
0/28
|
0.00%
0/27
|
|
General disorders
Chills
|
0.00%
0/30
|
0.00%
0/28
|
7.4%
2/27 • Number of events 3
|
|
General disorders
Fatigue
|
0.00%
0/30
|
0.00%
0/28
|
3.7%
1/27 • Number of events 1
|
|
General disorders
Feeling abnormal
|
0.00%
0/30
|
0.00%
0/28
|
3.7%
1/27 • Number of events 1
|
|
General disorders
Pain
|
0.00%
0/30
|
0.00%
0/28
|
3.7%
1/27 • Number of events 1
|
|
Infections and infestations
Pharyngitis
|
0.00%
0/30
|
0.00%
0/28
|
3.7%
1/27 • Number of events 1
|
|
Infections and infestations
Rhinitis
|
0.00%
0/30
|
0.00%
0/28
|
3.7%
1/27 • Number of events 1
|
|
Investigations
Electrocardiogram pr shortened
|
3.3%
1/30 • Number of events 1
|
0.00%
0/28
|
0.00%
0/27
|
|
Investigations
Electrocardiogram t wave abnormal
|
3.3%
1/30 • Number of events 1
|
0.00%
0/28
|
0.00%
0/27
|
|
Metabolism and nutrition disorders
Decreased appetite
|
0.00%
0/30
|
0.00%
0/28
|
3.7%
1/27 • Number of events 1
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
0.00%
0/30
|
3.6%
1/28 • Number of events 1
|
0.00%
0/27
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Melanocytic naevus
|
0.00%
0/30
|
0.00%
0/28
|
3.7%
1/27 • Number of events 1
|
|
Nervous system disorders
Dizziness
|
0.00%
0/30
|
0.00%
0/28
|
7.4%
2/27 • Number of events 2
|
|
Nervous system disorders
Dysaesthesia
|
0.00%
0/30
|
0.00%
0/28
|
7.4%
2/27 • Number of events 2
|
|
Nervous system disorders
Headache
|
0.00%
0/30
|
0.00%
0/28
|
7.4%
2/27 • Number of events 2
|
|
Nervous system disorders
Hypoaesthesia
|
0.00%
0/30
|
0.00%
0/28
|
3.7%
1/27 • Number of events 1
|
|
Nervous system disorders
Paraesthesia
|
0.00%
0/30
|
0.00%
0/28
|
3.7%
1/27 • Number of events 2
|
|
Psychiatric disorders
Anxiety
|
0.00%
0/30
|
0.00%
0/28
|
3.7%
1/27 • Number of events 1
|
|
Renal and urinary disorders
Pollakiuria
|
0.00%
0/30
|
3.6%
1/28 • Number of events 1
|
0.00%
0/27
|
|
Renal and urinary disorders
Semenuria
|
0.00%
0/18
|
0.00%
0/17
|
12.5%
2/16 • Number of events 3
|
|
Renal and urinary disorders
Urinary hesitation
|
0.00%
0/30
|
0.00%
0/28
|
3.7%
1/27 • Number of events 1
|
|
Reproductive system and breast disorders
Genital disorder male
|
0.00%
0/18
|
0.00%
0/17
|
6.2%
1/16 • Number of events 1
|
|
Reproductive system and breast disorders
Penile size reduced
|
0.00%
0/18
|
0.00%
0/17
|
6.2%
1/16 • Number of events 1
|
|
Reproductive system and breast disorders
Testicular disorder
|
0.00%
0/18
|
0.00%
0/17
|
6.2%
1/16 • Number of events 1
|
|
Reproductive system and breast disorders
Testicular pain
|
0.00%
0/18
|
0.00%
0/17
|
12.5%
2/16 • Number of events 2
|
|
Reproductive system and breast disorders
Testicular swelling
|
0.00%
0/18
|
0.00%
0/17
|
6.2%
1/16 • Number of events 1
|
|
Reproductive system and breast disorders
Testis discomfort
|
0.00%
0/18
|
0.00%
0/17
|
6.2%
1/16 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Dermatitis contact
|
0.00%
0/30
|
3.6%
1/28 • Number of events 1
|
7.4%
2/27 • Number of events 2
|
|
Skin and subcutaneous tissue disorders
Papule
|
0.00%
0/30
|
3.6%
1/28 • Number of events 1
|
3.7%
1/27 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/30
|
0.00%
0/28
|
7.4%
2/27 • Number of events 2
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/30
|
0.00%
0/28
|
7.4%
2/27 • Number of events 2
|
|
Skin and subcutaneous tissue disorders
Skin irritation
|
0.00%
0/30
|
0.00%
0/28
|
3.7%
1/27 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Urticaria
|
0.00%
0/30
|
3.6%
1/28 • Number of events 1
|
0.00%
0/27
|
|
Vascular disorders
Peripheral coldness
|
0.00%
0/30
|
0.00%
0/28
|
3.7%
1/27 • Number of events 1
|
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