Trial Outcomes & Findings for A Study of Evacetrapib (LY2484595) in Participants With Hepatic (Liver) Impairment (NCT NCT01836185)

NCT ID: NCT01836185

Last Updated: 2018-10-12

Results Overview

tlast is defined as the last time point with a measurable concentration of Evacetrapib.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

32 participants

Primary outcome timeframe

Predose on Day 1, and 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 120, 168, 216, 264, 312, and 336 hours after the Day 1 dose

Results posted on

2018-10-12

Participant Flow

Participant milestones

Participant milestones
Measure	Evacetrapib (Healthy) Group 1: 130 milligrams (mg) evacetrapib administered once, orally as a tablet to participants with normal hepatic function	Evacetrapib (Hepatic, Mild) Group 2: 130 mg evacetrapib administered once, orally as a tablet to participants with mild hepatic impairment	Evacetrapib (Hepatic, Moderate) Group 3: 130 mg evacetrapib administered once, orally as a tablet to participants with moderate hepatic impairment	Evacetrapib (Hepatic, Severe) Group 4: 130 mg evacetrapib administered once, orally as a tablet to participants with severe hepatic impairment
Overall Study STARTED	10	8	8	6
Overall Study Received Single Dose of Study Treatment	10	8	8	6
Overall Study COMPLETED	10	8	8	6
Overall Study NOT COMPLETED	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Study of Evacetrapib (LY2484595) in Participants With Hepatic (Liver) Impairment

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Evacetrapib (Healthy) n=10 Participants Group 1: 130 milligrams (mg) evacetrapib administered once, orally as a tablet to participants with normal hepatic function	Evacetrapib (Hepatic, Mild) n=8 Participants Group 2: 130 mg evacetrapib administered once, orally as a tablet to participants with mild hepatic impairment	Evacetrapib (Hepatic, Moderate) n=8 Participants Group 3: 130 mg evacetrapib administered once, orally as a tablet to participants with moderate hepatic impairment	Evacetrapib (Hepatic, Severe) n=6 Participants Group 4: 130 mg evacetrapib administered once, orally as a tablet to participants with severe hepatic impairment	Total n=32 Participants Total of all reporting groups
Age, Continuous	54.4 years STANDARD_DEVIATION 8.6 • n=5 Participants	54.1 years STANDARD_DEVIATION 2.9 • n=7 Participants	58.6 years STANDARD_DEVIATION 9.6 • n=5 Participants	57.8 years STANDARD_DEVIATION 4.7 • n=4 Participants	56.0 years STANDARD_DEVIATION 7.2 • n=21 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	4 Participants n=7 Participants	2 Participants n=5 Participants	1 Participants n=4 Participants	11 Participants n=21 Participants
Sex: Female, Male Male	6 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants	5 Participants n=4 Participants	21 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	8 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants	3 Participants n=4 Participants	17 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	2 Participants n=5 Participants	6 Participants n=7 Participants	4 Participants n=5 Participants	3 Participants n=4 Participants	15 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	2 Participants n=21 Participants
Race (NIH/OMB) White	9 Participants n=5 Participants	6 Participants n=7 Participants	8 Participants n=5 Participants	6 Participants n=4 Participants	29 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Region of Enrollment United States	10 Participants n=5 Participants	8 Participants n=7 Participants	8 Participants n=5 Participants	6 Participants n=4 Participants	32 Participants n=21 Participants

PRIMARY outcome

Timeframe: Predose on Day 1, and 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 120, 168, 216, 264, 312, and 336 hours after the Day 1 dose

Population: Participants who received at least 1 dose of study drug and had evaluable PK (AUC0-tlast) data.

tlast is defined as the last time point with a measurable concentration of Evacetrapib.

Outcome measures

Outcome measures
Measure	Evacetrapib (Healthy) n=10 Participants Group 1: 130 mg evacetrapib administered once, orally as a tablet to participants with normal hepatic function	Evacetrapib (Hepatic, Mild) n=8 Participants Group 2: 130 mg evacetrapib administered once, orally as a tablet to participants with mild hepatic impairment	Evacetrapib (Hepatic, Moderate) n=8 Participants Group 3: 130 mg evacetrapib administered once, orally as a tablet to participants with moderate hepatic impairment	Evacetrapib (Hepatic, Severe) n=6 Participants Group 4: 130 mg evacetrapib administered once, orally as a tablet to participants with severe hepatic impairment
Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Time Tlast (AUC0-tlast) of Evacetrapib	10700 nanogramshour per milliliter (ngh/mL) Geometric Coefficient of Variation 50	10500 nanogramshour per milliliter (ngh/mL) Geometric Coefficient of Variation 84	13200 nanogramshour per milliliter (ngh/mL) Geometric Coefficient of Variation 49	15800 nanogramshour per milliliter (ngh/mL) Geometric Coefficient of Variation 62

PRIMARY outcome

Timeframe: Predose on Day 1, and 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 120, 168, 216, 264, 312, and 336 hours after the Day 1 dose

Population: Participants who received at least 1 dose of study drug and had evaluable PK (Cmax) data.

Outcome measures

Outcome measures
Measure	Evacetrapib (Healthy) n=10 Participants Group 1: 130 mg evacetrapib administered once, orally as a tablet to participants with normal hepatic function	Evacetrapib (Hepatic, Mild) n=8 Participants Group 2: 130 mg evacetrapib administered once, orally as a tablet to participants with mild hepatic impairment	Evacetrapib (Hepatic, Moderate) n=8 Participants Group 3: 130 mg evacetrapib administered once, orally as a tablet to participants with moderate hepatic impairment	Evacetrapib (Hepatic, Severe) n=6 Participants Group 4: 130 mg evacetrapib administered once, orally as a tablet to participants with severe hepatic impairment
PK: Maximum Observed Concentration (Cmax) of Evacetrapib	605 ng/mL Geometric Coefficient of Variation 98	609 ng/mL Geometric Coefficient of Variation 144	591 ng/mL Geometric Coefficient of Variation 58	478 ng/mL Geometric Coefficient of Variation 51

PRIMARY outcome

Timeframe: Predose on Day 1, and 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 120, 168, 216, 264, 312, and 336 hours after the Day 1 dose

Population: Participants who received at least one dose of study drug and had evaluable PK data.

Outcome measures

Outcome measures
Measure	Evacetrapib (Healthy) n=10 Participants Group 1: 130 mg evacetrapib administered once, orally as a tablet to participants with normal hepatic function	Evacetrapib (Hepatic, Mild) n=8 Participants Group 2: 130 mg evacetrapib administered once, orally as a tablet to participants with mild hepatic impairment	Evacetrapib (Hepatic, Moderate) n=8 Participants Group 3: 130 mg evacetrapib administered once, orally as a tablet to participants with moderate hepatic impairment	Evacetrapib (Hepatic, Severe) n=6 Participants Group 4: 130 mg evacetrapib administered once, orally as a tablet to participants with severe hepatic impairment
PK: Time of Maximum Observed Drug Concentration (Tmax) of Evacetrapib	3 h Interval 2.0 to 6.0	3 h Interval 1.0 to 4.0	3 h Interval 2.0 to 4.0	3 h Interval 2.0 to 6.0

Adverse Events

Evacetrapib (Healthy)

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Evacetrapib (Hepatic, Mild)

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Evacetrapib (Hepatic, Moderate)

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Evacetrapib (Hepatic, Severe)

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

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

Measure	Evacetrapib (Healthy) n=10 participants at risk Group 1: 130 mg evacetrapib administered once, orally as a tablet to participants with normal hepatic function	Evacetrapib (Hepatic, Mild) n=8 participants at risk Group 2: 130 mg evacetrapib administered once, orally as a tablet to participants with mild hepatic impairment	Evacetrapib (Hepatic, Moderate) n=8 participants at risk Group 3: 130 mg evacetrapib administered once, orally, as a tablet to participants with moderate hepatic impairment	Evacetrapib (Hepatic, Severe) n=6 participants at risk Group 4: 130 mg evacetrapib administered once, orally as a tablet to participants with severe hepatic impairment
Gastrointestinal disorders Abdominal pain	0.00% 0/10 • Randomization to study completion (Up To 41 Days)	0.00% 0/8 • Randomization to study completion (Up To 41 Days)	0.00% 0/8 • Randomization to study completion (Up To 41 Days)	16.7% 1/6 • Number of events 1 • Randomization to study completion (Up To 41 Days)
Gastrointestinal disorders Abdominal pain upper	0.00% 0/10 • Randomization to study completion (Up To 41 Days)	0.00% 0/8 • Randomization to study completion (Up To 41 Days)	12.5% 1/8 • Number of events 1 • Randomization to study completion (Up To 41 Days)	0.00% 0/6 • Randomization to study completion (Up To 41 Days)
Gastrointestinal disorders Constipation	0.00% 0/10 • Randomization to study completion (Up To 41 Days)	0.00% 0/8 • Randomization to study completion (Up To 41 Days)	12.5% 1/8 • Number of events 1 • Randomization to study completion (Up To 41 Days)	16.7% 1/6 • Number of events 1 • Randomization to study completion (Up To 41 Days)
Gastrointestinal disorders Diarrhoea	0.00% 0/10 • Randomization to study completion (Up To 41 Days)	0.00% 0/8 • Randomization to study completion (Up To 41 Days)	12.5% 1/8 • Number of events 1 • Randomization to study completion (Up To 41 Days)	33.3% 2/6 • Number of events 3 • Randomization to study completion (Up To 41 Days)
Gastrointestinal disorders Flatulence	10.0% 1/10 • Number of events 1 • Randomization to study completion (Up To 41 Days)	12.5% 1/8 • Number of events 1 • Randomization to study completion (Up To 41 Days)	0.00% 0/8 • Randomization to study completion (Up To 41 Days)	0.00% 0/6 • Randomization to study completion (Up To 41 Days)
Gastrointestinal disorders Vomiting	0.00% 0/10 • Randomization to study completion (Up To 41 Days)	0.00% 0/8 • Randomization to study completion (Up To 41 Days)	12.5% 1/8 • Number of events 1 • Randomization to study completion (Up To 41 Days)	16.7% 1/6 • Number of events 1 • Randomization to study completion (Up To 41 Days)
Infections and infestations Viral infection	0.00% 0/10 • Randomization to study completion (Up To 41 Days)	12.5% 1/8 • Number of events 1 • Randomization to study completion (Up To 41 Days)	0.00% 0/8 • Randomization to study completion (Up To 41 Days)	0.00% 0/6 • Randomization to study completion (Up To 41 Days)
Injury, poisoning and procedural complications Laceration	0.00% 0/10 • Randomization to study completion (Up To 41 Days)	0.00% 0/8 • Randomization to study completion (Up To 41 Days)	12.5% 1/8 • Number of events 1 • Randomization to study completion (Up To 41 Days)	0.00% 0/6 • Randomization to study completion (Up To 41 Days)
Nervous system disorders Dizziness	0.00% 0/10 • Randomization to study completion (Up To 41 Days)	0.00% 0/8 • Randomization to study completion (Up To 41 Days)	12.5% 1/8 • Number of events 1 • Randomization to study completion (Up To 41 Days)	0.00% 0/6 • Randomization to study completion (Up To 41 Days)
Nervous system disorders Headache	10.0% 1/10 • Number of events 1 • Randomization to study completion (Up To 41 Days)	0.00% 0/8 • Randomization to study completion (Up To 41 Days)	0.00% 0/8 • Randomization to study completion (Up To 41 Days)	16.7% 1/6 • Number of events 1 • Randomization to study completion (Up To 41 Days)
Nervous system disorders Somnolence	0.00% 0/10 • Randomization to study completion (Up To 41 Days)	0.00% 0/8 • Randomization to study completion (Up To 41 Days)	12.5% 1/8 • Number of events 1 • Randomization to study completion (Up To 41 Days)	0.00% 0/6 • Randomization to study completion (Up To 41 Days)
Skin and subcutaneous tissue disorders Dermatitis contact	10.0% 1/10 • Number of events 1 • Randomization to study completion (Up To 41 Days)	0.00% 0/8 • Randomization to study completion (Up To 41 Days)	0.00% 0/8 • Randomization to study completion (Up To 41 Days)	0.00% 0/6 • Randomization to study completion (Up To 41 Days)
Skin and subcutaneous tissue disorders Ecchymosis	0.00% 0/10 • Randomization to study completion (Up To 41 Days)	0.00% 0/8 • Randomization to study completion (Up To 41 Days)	0.00% 0/8 • Randomization to study completion (Up To 41 Days)	16.7% 1/6 • Number of events 1 • Randomization to study completion (Up To 41 Days)
Skin and subcutaneous tissue disorders Piloerection	0.00% 0/10 • Randomization to study completion (Up To 41 Days)	12.5% 1/8 • Number of events 1 • Randomization to study completion (Up To 41 Days)	0.00% 0/8 • Randomization to study completion (Up To 41 Days)	0.00% 0/6 • Randomization to study completion (Up To 41 Days)
Skin and subcutaneous tissue disorders Rash papular	0.00% 0/10 • Randomization to study completion (Up To 41 Days)	12.5% 1/8 • Number of events 1 • Randomization to study completion (Up To 41 Days)	0.00% 0/8 • Randomization to study completion (Up To 41 Days)	0.00% 0/6 • Randomization to study completion (Up To 41 Days)