Trial Outcomes & Findings for A Study of LY2140023 in Hepatically-Impaired Participants (NCT NCT01475136)
NCT ID: NCT01475136
Last Updated: 2021-09-22
Results Overview
LY404039 is the active metabolite of LY2140023. AUC from zero to infinity AUC(0-∞) is presented.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
37 participants
Primary outcome timeframe
Predose and 0.5, 1, 2, 3, 4, 6, 9, 12, 16, 24, 36, and 48 hours postdose
Results posted on
2021-09-22
Participant Flow
Participants (Pts) were enrolled in Group 3 (moderate hepatic impairment) after satisfactory interim safety and pharmacokinetic (PK) data was obtained from ≥3 Pts in Group 2 (mild hepatic impairment). Pts were enrolled in Group 4 (severe hepatic impairment) after satisfactory interim safety and PK data was obtained from ≥3 Pts in Group 3.
Participant milestones
| Measure |
LY2140023-Normal Hepatic Function
Participants with normal hepatic function received a single oral dose of 80 milligrams (mg) LY2140023 on Day 1.
|
LY2140023-Mild Hepatic Impairment
Participants with mild hepatic impairment received a single oral dose of 80 mg LY2140023 on Day 1.
|
LY2140023-Moderate Hepatic Impairment
Participants with moderate hepatic impairment received a single oral dose of 80 mg LY2140023 on Day 1.
|
LY2140023-Severe Hepatic Impairment
Participants with severe hepatic impairment received a single oral dose of 80 mg LY2140023on Day 1.
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
7
|
9
|
9
|
12
|
|
Overall Study
Received 1 Dose of Study Drug
|
7
|
6
|
6
|
7
|
|
Overall Study
COMPLETED
|
6
|
6
|
6
|
7
|
|
Overall Study
NOT COMPLETED
|
1
|
3
|
3
|
5
|
Reasons for withdrawal
| Measure |
LY2140023-Normal Hepatic Function
Participants with normal hepatic function received a single oral dose of 80 milligrams (mg) LY2140023 on Day 1.
|
LY2140023-Mild Hepatic Impairment
Participants with mild hepatic impairment received a single oral dose of 80 mg LY2140023 on Day 1.
|
LY2140023-Moderate Hepatic Impairment
Participants with moderate hepatic impairment received a single oral dose of 80 mg LY2140023 on Day 1.
|
LY2140023-Severe Hepatic Impairment
Participants with severe hepatic impairment received a single oral dose of 80 mg LY2140023on Day 1.
|
|---|---|---|---|---|
|
Overall Study
Sponsor Decision
|
0
|
1
|
0
|
0
|
|
Overall Study
Entry Criteria Not Met
|
0
|
2
|
3
|
1
|
|
Overall Study
Withdrawal by Subject
|
0
|
0
|
0
|
2
|
|
Overall Study
Adverse Event
|
1
|
0
|
0
|
1
|
|
Overall Study
Death
|
0
|
0
|
0
|
1
|
Baseline Characteristics
A Study of LY2140023 in Hepatically-Impaired Participants
Baseline characteristics by cohort
| Measure |
LY2140023-Normal Hepatic Function
n=7 Participants
Participants with normal hepatic function received a single oral dose of 80 mg LY2140023 on Day 1.
|
LY2140023-Mild Hepatic Impairment
n=9 Participants
Participants with mild hepatic impairment received a single oral dose of 80 mg LY2140023 on Day 1.
|
LY2140023-Moderate Hepatic Impairment
n=9 Participants
Participants with moderate hepatic impairment received a single oral dose of 80 mg LY2140023 on Day 1.
|
LY2140023-Severe Hepatic Impairment
n=12 Participants
Participants with severe hepatic impairment received a single oral dose of 80 mg LY2140023on Day 1.
|
Total
n=37 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
56.9 years
STANDARD_DEVIATION 2.5 • n=99 Participants
|
57.4 years
STANDARD_DEVIATION 5.9 • n=107 Participants
|
56.8 years
STANDARD_DEVIATION 4.0 • n=206 Participants
|
53.9 years
STANDARD_DEVIATION 7.3 • n=7 Participants
|
56.0 years
STANDARD_DEVIATION 5.6 • n=31 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=99 Participants
|
3 Participants
n=107 Participants
|
6 Participants
n=206 Participants
|
5 Participants
n=7 Participants
|
18 Participants
n=31 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=99 Participants
|
6 Participants
n=107 Participants
|
3 Participants
n=206 Participants
|
7 Participants
n=7 Participants
|
19 Participants
n=31 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
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
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
7 Participants
n=99 Participants
|
9 Participants
n=107 Participants
|
9 Participants
n=206 Participants
|
12 Participants
n=7 Participants
|
37 Participants
n=31 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
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
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
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
|
|
Race (NIH/OMB)
Asian
|
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
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
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
|
|
Race (NIH/OMB)
Black or African American
|
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
|
|
Race (NIH/OMB)
White
|
7 Participants
n=99 Participants
|
9 Participants
n=107 Participants
|
9 Participants
n=206 Participants
|
12 Participants
n=7 Participants
|
37 Participants
n=31 Participants
|
|
Race (NIH/OMB)
More than one race
|
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
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
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
|
|
Region of Enrollment
Hungary
|
4 participants
n=99 Participants
|
2 participants
n=107 Participants
|
5 participants
n=206 Participants
|
12 participants
n=7 Participants
|
23 participants
n=31 Participants
|
|
Region of Enrollment
Germany
|
3 participants
n=99 Participants
|
7 participants
n=107 Participants
|
4 participants
n=206 Participants
|
0 participants
n=7 Participants
|
14 participants
n=31 Participants
|
PRIMARY outcome
Timeframe: Predose and 0.5, 1, 2, 3, 4, 6, 9, 12, 16, 24, 36, and 48 hours postdosePopulation: All participants who received 1 dose of LY2140023, did not have an incidence of vomiting within 5 hours postdose, and had evaluable AUC(0-∞) data.
LY404039 is the active metabolite of LY2140023. AUC from zero to infinity AUC(0-∞) is presented.
Outcome measures
| Measure |
LY2140023-Normal Hepatic Function
n=5 Participants
Participants with normal hepatic function received a single oral dose of 80 mg LY2140023 on Day 1.
|
LY2140023-Mild Hepatic Impairment
n=6 Participants
Participants with mild hepatic impairment received a single oral dose of 80 mg LY2140023 on Day 1.
|
LY2140023-Moderate Hepatic Impairment
n=6 Participants
Participants with moderate hepatic impairment received a single oral dose of 80 mg LY2140023 on Day 1.
|
LY2140023-Severe Hepatic Impairment
n=5 Participants
Participants with severe hepatic impairment received a single oral dose of 80 mg LY2140023on Day 1.
|
|---|---|---|---|---|
|
Pharmacokinetics: Area Under the Concentration Time Curve (AUC) of LY2140023 and LY404039
LY404039
|
2710 nanograms*hours per milliliter (ng*h/mL)
Geometric Coefficient of Variation 16
|
3290 nanograms*hours per milliliter (ng*h/mL)
Geometric Coefficient of Variation 28
|
2570 nanograms*hours per milliliter (ng*h/mL)
Geometric Coefficient of Variation 28
|
2640 nanograms*hours per milliliter (ng*h/mL)
Geometric Coefficient of Variation 33
|
|
Pharmacokinetics: Area Under the Concentration Time Curve (AUC) of LY2140023 and LY404039
LY2140023
|
1420 nanograms*hours per milliliter (ng*h/mL)
Geometric Coefficient of Variation 34
|
1360 nanograms*hours per milliliter (ng*h/mL)
Geometric Coefficient of Variation 30
|
836 nanograms*hours per milliliter (ng*h/mL)
Geometric Coefficient of Variation 57
|
926 nanograms*hours per milliliter (ng*h/mL)
Geometric Coefficient of Variation 22
|
PRIMARY outcome
Timeframe: Predose and 0.5, 1, 2, 3, 4, 6, 9, 12, 16, 24, 36, and 48 hours postdosePopulation: All participants who received 1 dose of LY2140023, did not have an incidence of vomiting within 5 hours postdose, and had evaluable Cmax data.
LY404039 is the active metabolite of LY2140023.
Outcome measures
| Measure |
LY2140023-Normal Hepatic Function
n=5 Participants
Participants with normal hepatic function received a single oral dose of 80 mg LY2140023 on Day 1.
|
LY2140023-Mild Hepatic Impairment
n=6 Participants
Participants with mild hepatic impairment received a single oral dose of 80 mg LY2140023 on Day 1.
|
LY2140023-Moderate Hepatic Impairment
n=6 Participants
Participants with moderate hepatic impairment received a single oral dose of 80 mg LY2140023 on Day 1.
|
LY2140023-Severe Hepatic Impairment
n=5 Participants
Participants with severe hepatic impairment received a single oral dose of 80 mg LY2140023on Day 1.
|
|---|---|---|---|---|
|
Pharmacokinetics: Maximum Observed Drug Concentration (Cmax) of LY2140023 and LY404039
LY2140023
|
332 nanograms/milliliter (ng/mL)
Geometric Coefficient of Variation 27
|
305 nanograms/milliliter (ng/mL)
Geometric Coefficient of Variation 29
|
211 nanograms/milliliter (ng/mL)
Geometric Coefficient of Variation 41
|
194 nanograms/milliliter (ng/mL)
Geometric Coefficient of Variation 25
|
|
Pharmacokinetics: Maximum Observed Drug Concentration (Cmax) of LY2140023 and LY404039
LY404039
|
440 nanograms/milliliter (ng/mL)
Geometric Coefficient of Variation 10
|
517 nanograms/milliliter (ng/mL)
Geometric Coefficient of Variation 23
|
431 nanograms/milliliter (ng/mL)
Geometric Coefficient of Variation 28
|
403 nanograms/milliliter (ng/mL)
Geometric Coefficient of Variation 28
|
PRIMARY outcome
Timeframe: Predose and 0.5, 1, 2, 3, 4, 6, 9, 12, 16, 24, 36, and 48 hours postdosePopulation: All participants who received 1 dose of LY2140023, did not have an incidence of vomiting within 5 hours postdose, and had evaluable Tmax data.
LY404039 is the active metabolite of LY2140023.
Outcome measures
| Measure |
LY2140023-Normal Hepatic Function
n=5 Participants
Participants with normal hepatic function received a single oral dose of 80 mg LY2140023 on Day 1.
|
LY2140023-Mild Hepatic Impairment
n=6 Participants
Participants with mild hepatic impairment received a single oral dose of 80 mg LY2140023 on Day 1.
|
LY2140023-Moderate Hepatic Impairment
n=6 Participants
Participants with moderate hepatic impairment received a single oral dose of 80 mg LY2140023 on Day 1.
|
LY2140023-Severe Hepatic Impairment
n=5 Participants
Participants with severe hepatic impairment received a single oral dose of 80 mg LY2140023on Day 1.
|
|---|---|---|---|---|
|
Pharmacokinetics: Time of Maximal Concentration (Tmax) of LY2140023 and LY404039
LY2140023
|
3.00 hours
Interval 2.0 to 4.0
|
2.50 hours
Interval 2.0 to 3.0
|
2.50 hours
Interval 1.0 to 4.0
|
2.00 hours
Interval 2.0 to 3.0
|
|
Pharmacokinetics: Time of Maximal Concentration (Tmax) of LY2140023 and LY404039
LY404039
|
4.00 hours
Interval 3.0 to 4.0
|
4.00 hours
Interval 3.0 to 4.0
|
3.50 hours
Interval 2.0 to 4.0
|
4.00 hours
Interval 3.0 to 4.0
|
Adverse Events
LY2140023-Normal Hepatic Function
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
LY2140023-Mild Hepatic Impairment
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
LY2140023-Moderate Hepatic Impairment
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
LY2140023-Severe Hepatic Impairment
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
LY2140023-Normal Hepatic Function
n=7 participants at risk
Participants with normal hepatic function received a single oral dose of 80 mg LY2140023 on Day 1.
|
LY2140023-Mild Hepatic Impairment
n=6 participants at risk
Participants with mild hepatic impairment received a single oral dose of 80 mg LY2140023 on Day 1.
|
LY2140023-Moderate Hepatic Impairment
n=6 participants at risk
Participants with moderate hepatic impairment received a single oral dose of 80 mg LY2140023 on Day 1.
|
LY2140023-Severe Hepatic Impairment
n=7 participants at risk
Participants with severe hepatic impairment received a single oral dose of 80 mg LY2140023on Day 1.
|
|---|---|---|---|---|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
14.3%
1/7 • Number of events 1
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/7
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/7
|
16.7%
1/6 • Number of events 1
|
0.00%
0/6
|
0.00%
0/7
|
|
Gastrointestinal disorders
Nausea
|
42.9%
3/7 • Number of events 3
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/7
|
|
Gastrointestinal disorders
Vomiting
|
14.3%
1/7 • Number of events 1
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/7
|
|
General disorders
Chest pain
|
0.00%
0/7
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
0.00%
0/7
|
|
General disorders
Fatigue
|
14.3%
1/7 • Number of events 1
|
33.3%
2/6 • Number of events 2
|
33.3%
2/6 • Number of events 2
|
0.00%
0/7
|
|
Investigations
Blood creatine phosphokinase increased
|
0.00%
0/7
|
16.7%
1/6 • Number of events 1
|
0.00%
0/6
|
0.00%
0/7
|
|
Nervous system disorders
Dizziness
|
0.00%
0/7
|
33.3%
2/6 • Number of events 2
|
0.00%
0/6
|
0.00%
0/7
|
|
Nervous system disorders
Dizziness postural
|
14.3%
1/7 • Number of events 1
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/7
|
|
Nervous system disorders
Headache
|
0.00%
0/7
|
16.7%
1/6 • Number of events 1
|
0.00%
0/6
|
0.00%
0/7
|
|
Nervous system disorders
Presyncope
|
0.00%
0/7
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
0.00%
0/7
|
|
Psychiatric disorders
Insomnia
|
0.00%
0/7
|
16.7%
1/6 • Number of events 1
|
0.00%
0/6
|
0.00%
0/7
|
|
Psychiatric disorders
Sleep disorder
|
0.00%
0/7
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
0.00%
0/7
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/7
|
0.00%
0/6
|
16.7%
1/6 • Number of events 1
|
0.00%
0/7
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/7
|
16.7%
1/6 • Number of events 1
|
0.00%
0/6
|
0.00%
0/7
|
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