Trial Outcomes & Findings for A Study of Evacetrapib With Selected Statins in Healthy Chinese Participants (NCT NCT02156492)

Results Overview

Pharmacokinetic (PK) parameter estimates from evacetrapib concentrations following single dose and daily dose of 130 mg evacetrapib.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

62 participants

Primary outcome timeframe

Part 1: Day 1 Predose 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 144, and 168 hours Postdose; Part 2 Day 14 Predose 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24 hours Postdose

Results posted on

2018-10-10

Participant Flow

Participant milestones

Participant milestones
Measure	Cohort A: Evacetrapib Single and Multiple Dose Part 1, Cohort A, Period 1, Participants will receive a single oral 130 mg dose of evacetrapib. Part 1, Cohort A, Period 2, Participants will receive multiple doses of evacetrapib 130 mg for 14 days.	Cohort B: Evacetrapib and Simvastatin Part 2, Cohorts B, Period 1, Participants will receive simvastatin 40 mg orally, once daily on Days 1 - 4 Part 2, Cohorts B, Period 2, Participants will receive a single oral 130 mg dose of evacetrapib on Days 5-14 Part 2, Cohorts B, Period 3, Participants will receive evacetrapib 130 mg and simvastatin 40mg orally, once daily on Days 15 - 22.	Cohort C: Evacetrapib and Atorvastatin Part 2, Cohorts C, Period 1, Participants will receive atorvastatin orally, once daily on Days 1 - 4. Part 2, Cohorts C, Period 2, Participants will receive a single oral 130 mg dose of evacetrapib on Days 5-14 Part 2, Cohorts C, Period 3, Participants will receive evacetrapib 130 mg orally and atorvastatin 20 mg orally, once daily on Days 15 - 22.
Period 1 STARTED	16	24	22
Period 1 Received at Least One Dose of Study Drug	16	24	22
Period 1 COMPLETED	16	23	22
Period 1 NOT COMPLETED	0	1	0
Period 2 STARTED	16	23	22
Period 2 COMPLETED	16	23	22
Period 2 NOT COMPLETED	0	0	0
Period 3 STARTED	0	23	22
Period 3 COMPLETED	0	22	22
Period 3 NOT COMPLETED	0	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Cohort A: Evacetrapib Single and Multiple Dose Part 1, Cohort A, Period 1, Participants will receive a single oral 130 mg dose of evacetrapib. Part 1, Cohort A, Period 2, Participants will receive multiple doses of evacetrapib 130 mg for 14 days.	Cohort B: Evacetrapib and Simvastatin Part 2, Cohorts B, Period 1, Participants will receive simvastatin 40 mg orally, once daily on Days 1 - 4 Part 2, Cohorts B, Period 2, Participants will receive a single oral 130 mg dose of evacetrapib on Days 5-14 Part 2, Cohorts B, Period 3, Participants will receive evacetrapib 130 mg and simvastatin 40mg orally, once daily on Days 15 - 22.	Cohort C: Evacetrapib and Atorvastatin Part 2, Cohorts C, Period 1, Participants will receive atorvastatin orally, once daily on Days 1 - 4. Part 2, Cohorts C, Period 2, Participants will receive a single oral 130 mg dose of evacetrapib on Days 5-14 Part 2, Cohorts C, Period 3, Participants will receive evacetrapib 130 mg orally and atorvastatin 20 mg orally, once daily on Days 15 - 22.
Period 1 No Reason Given	0	1	0
Period 3 Adverse Event	0	1	0

Baseline Characteristics

A Study of Evacetrapib With Selected Statins in Healthy Chinese Participants

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort A n=16 Participants Part 1, Cohort A, Period 1, Participants will receive a single oral 130 mg dose of evacetrapib. Part 1, Cohort A, Period 2, Participants will receive multiple doses of evacetrapib 130 mg for 14 days.	Cohort B n=24 Participants Part 2, Cohorts B, Period 1, Participants will receive simvastatin 40 mg orally, once daily on Days 1 - 4. Part 2, Cohorts B, Period 2, Participants will receive a single oral 130 mg dose of evacetrapib on Days 5-14 Part 2, Cohorts B, Period 3, Participants will receive evacetrapib 130 mg and simvastatin 40mg orally, once daily on Days 15 - 22.	Cohort C n=22 Participants Part 2, Cohorts C, Period 1, Participants will receive atorvastatin orally, once daily on Days 1 - 4. Part 2, Cohorts C, Period 2, Participants will receive a single oral 130 mg dose of evacetrapib on Days 5-14 Part 2, Cohorts C, Period 3, Participants will receive evacetrapib 130 mg orally and atorvastatin 20 mg orally, once daily on Days 15 - 22.	Total n=62 Participants Total of all reporting groups
Age, Continuous	29.1 years STANDARD_DEVIATION 8.0 • n=5 Participants	27.5 years STANDARD_DEVIATION 2.9 • n=7 Participants	27.9 years STANDARD_DEVIATION 4.9 • n=5 Participants	28.02 years STANDARD_DEVIATION 5.25 • n=4 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	5 Participants n=4 Participants
Sex: Female, Male Male	13 Participants n=5 Participants	24 Participants n=7 Participants	20 Participants n=5 Participants	57 Participants n=4 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
Race (NIH/OMB) Asian	16 Participants n=5 Participants	24 Participants n=7 Participants	22 Participants n=5 Participants	62 Participants n=4 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
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 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
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
Region of Enrollment China	16 Participants n=5 Participants	24 Participants n=7 Participants	22 Participants n=5 Participants	62 Participants n=4 Participants

PRIMARY outcome

Timeframe: Part 1: Day 1 Predose 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 144, and 168 hours Postdose; Part 2 Day 14 Predose 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24 hours Postdose

Population: All participants who received at least one dose of study drug in Cohort A.

Pharmacokinetic (PK) parameter estimates from evacetrapib concentrations following single dose and daily dose of 130 mg evacetrapib.

Outcome measures

Outcome measures
Measure	Evacetrapib Single and Multiple Dose n=16 Participants Part 1, Cohort A, Period 1, Participants will receive a single oral 130 mg dose of evacetrapib. Part 1, Cohort A, Period 2, Participants will receive multiple doses of evacetrapib 130 mg for 14 days.	Evacetrapib Daily and Atorvastatin Part 2, Cohorts C, Period 2, Participants will receive a single oral 130 mg dose of evacetrapib on Days 5-14. Part 2, Cohorts C, Period 3, Participants will receive evacetrapib 130 mg orally and atorvastatin 20 mg orally, once daily on Days 15 - 22.
Pharmacokinetics (PK): Area Under Curve (AUC 0-inf) of Evacetrapib Day 1	7700 nanogram * hour per milliliter (ng*h/mL) Geometric Coefficient of Variation 74	—
Pharmacokinetics (PK): Area Under Curve (AUC 0-inf) of Evacetrapib Day 14	23600 nanogram * hour per milliliter (ng*h/mL) Geometric Coefficient of Variation 33	—

PRIMARY outcome

Timeframe: Part 1: Day 1 and Day 14 Predose 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 144, and 168 hours Postdose; Part 2 Day 14: Predose 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours Postdose

Population: All participants who received at least one dose of study drug in Cohort A.

Pharmacokinetic parameter estimates from evacetrapib following single dose and daily doses of 130 mg.

Outcome measures

Outcome measures
Measure	Evacetrapib Single and Multiple Dose n=16 Participants Part 1, Cohort A, Period 1, Participants will receive a single oral 130 mg dose of evacetrapib. Part 1, Cohort A, Period 2, Participants will receive multiple doses of evacetrapib 130 mg for 14 days.	Evacetrapib Daily and Atorvastatin Part 2, Cohorts C, Period 2, Participants will receive a single oral 130 mg dose of evacetrapib on Days 5-14. Part 2, Cohorts C, Period 3, Participants will receive evacetrapib 130 mg orally and atorvastatin 20 mg orally, once daily on Days 15 - 22.
PK: Maximum Concentration (Cmax) of Evacetrapib Single Dose Day 1	418 ng/mL Geometric Coefficient of Variation 118	—
PK: Maximum Concentration (Cmax) of Evacetrapib Multiple Dose Day 14	954 ng/mL Geometric Coefficient of Variation 52	—

PRIMARY outcome

Timeframe: Part 1: Day 1 Predose on Day 1 or Day 14 and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 144, and 168 hours postdose. Part 2: Predose on Day 14 at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours post dose.

Population: All participants who received at least one dose of study drug in Cohort A.

Pharmacokinetic parameter estimates of evacetrapib following single and daily doses of 130 mg evacetrapib.

Outcome measures

Outcome measures
Measure	Evacetrapib Single and Multiple Dose n=16 Participants Part 1, Cohort A, Period 1, Participants will receive a single oral 130 mg dose of evacetrapib. Part 1, Cohort A, Period 2, Participants will receive multiple doses of evacetrapib 130 mg for 14 days.	Evacetrapib Daily and Atorvastatin Part 2, Cohorts C, Period 2, Participants will receive a single oral 130 mg dose of evacetrapib on Days 5-14. Part 2, Cohorts C, Period 3, Participants will receive evacetrapib 130 mg orally and atorvastatin 20 mg orally, once daily on Days 15 - 22.
PK: Time to Maximum Concentration (Tmax) of Evacetrapib Single Dose Day 1	3.00 hours (h) Interval 2.0 to 6.0	—
PK: Time to Maximum Concentration (Tmax) of Evacetrapib Daily Dose Day 14	3.00 hours (h) Interval 2.0 to 4.0	—

PRIMARY outcome

Timeframe: Part 2: Day 14 and 22 Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours Postdose

Population: All participants who received at least one dose of study drug in Cohort B and C and had evaluable PK data

Pharmacokinetic parameter estimates of evacetrapib following 130 mg evacetrapib daily alone or with 40 mg simvastatin or 20 mg atorvastatin daily AUC (0-24).

Outcome measures

Outcome measures
Measure	Evacetrapib Single and Multiple Dose n=23 Participants Part 1, Cohort A, Period 1, Participants will receive a single oral 130 mg dose of evacetrapib. Part 1, Cohort A, Period 2, Participants will receive multiple doses of evacetrapib 130 mg for 14 days.	Evacetrapib Daily and Atorvastatin n=22 Participants Part 2, Cohorts C, Period 2, Participants will receive a single oral 130 mg dose of evacetrapib on Days 5-14. Part 2, Cohorts C, Period 3, Participants will receive evacetrapib 130 mg orally and atorvastatin 20 mg orally, once daily on Days 15 - 22.
PK: AUC of Evacetrapib Alone and With Simvastatin or Atorvastatin Days 5-14	10700 ng*h/mL Geometric Coefficient of Variation 36	10600 ng*h/mL Geometric Coefficient of Variation 30
PK: AUC of Evacetrapib Alone and With Simvastatin or Atorvastatin Days 15-22	9640 ng*h/mL Geometric Coefficient of Variation 48	9480 ng*h/mL Geometric Coefficient of Variation 53

PRIMARY outcome

Timeframe: Part 2: Day 14 and 22 Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours Postdose.

Population: All participants who received at least one dose of study drug in Cohort B and C and had evaluable PK data.

Pharmacokinetic parameter estimates of evacetrapib following 130 mg evacetrapib daily alone or with 40 mg simvastatin or 20 mg atorvastatin daily.

Outcome measures

Outcome measures
Measure	Evacetrapib Single and Multiple Dose n=23 Participants Part 1, Cohort A, Period 1, Participants will receive a single oral 130 mg dose of evacetrapib. Part 1, Cohort A, Period 2, Participants will receive multiple doses of evacetrapib 130 mg for 14 days.	Evacetrapib Daily and Atorvastatin n=22 Participants Part 2, Cohorts C, Period 2, Participants will receive a single oral 130 mg dose of evacetrapib on Days 5-14. Part 2, Cohorts C, Period 3, Participants will receive evacetrapib 130 mg orally and atorvastatin 20 mg orally, once daily on Days 15 - 22.
PK: Cmax of Evacetrapib Alone and With Simvastatin or Atorvastatin Days 5-14	1180 ng/mL Geometric Coefficient of Variation 52	1120 ng/mL Geometric Coefficient of Variation 36
PK: Cmax of Evacetrapib Alone and With Simvastatin or Atorvastatin Days 15- 22	1020 ng/mL Geometric Coefficient of Variation 68	1000 ng/mL Geometric Coefficient of Variation 73

PRIMARY outcome

Timeframe: Part 2: Predose on Day 14 and 22 and at 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose.

Population: All participants who received at least one dose of study drug in Cohort B and C and had evaluable PK data.

Pharmacokinetic parameter estimates of Tmax of evacetrapib following 130 mg daily dose alone or with 40 mg Simvastatin or 20 mg Atorvastatin. Tmax of simvastatin and atorvastatin.

Outcome measures

Outcome measures
Measure	Evacetrapib Single and Multiple Dose n=23 Participants Part 1, Cohort A, Period 1, Participants will receive a single oral 130 mg dose of evacetrapib. Part 1, Cohort A, Period 2, Participants will receive multiple doses of evacetrapib 130 mg for 14 days.	Evacetrapib Daily and Atorvastatin n=22 Participants Part 2, Cohorts C, Period 2, Participants will receive a single oral 130 mg dose of evacetrapib on Days 5-14. Part 2, Cohorts C, Period 3, Participants will receive evacetrapib 130 mg orally and atorvastatin 20 mg orally, once daily on Days 15 - 22.
PK: Tmax of Evacetrapib Alone and With Simvastatin or Atorvastatin Days 5-14	3.00 h Interval 2.0 to 4.0	3.00 h Interval 2.0 to 6.0
PK: Tmax of Evacetrapib Alone and With Simvastatin or Atorvastatin Days 15- 22	3.00 h Interval 2.0 to 4.0	3.00 h Interval 2.0 to 4.0

SECONDARY outcome

Timeframe: Single Dose Day 2 and Multiple Dose Day 22

Population: All participants who received at least one dose of study drug in Cohort A.

Outcome measures

Outcome measures
Measure	Evacetrapib Single and Multiple Dose n=16 Participants Part 1, Cohort A, Period 1, Participants will receive a single oral 130 mg dose of evacetrapib. Part 1, Cohort A, Period 2, Participants will receive multiple doses of evacetrapib 130 mg for 14 days.	Evacetrapib Daily and Atorvastatin n=16 Participants Part 2, Cohorts C, Period 2, Participants will receive a single oral 130 mg dose of evacetrapib on Days 5-14. Part 2, Cohorts C, Period 3, Participants will receive evacetrapib 130 mg orally and atorvastatin 20 mg orally, once daily on Days 15 - 22.
Effect of Evacetrapib Single and Multiple Doses on High Density Lipoprotein Cholesterol (HDL-C), Low Density Lipoprotein Cholesterol (LDL-C), and Triglycerides (TG) HDL-C	1.641 millimoles per liter (mmol/L) Standard Deviation 0.211	2.676 millimoles per liter (mmol/L) Standard Deviation 0.373
Effect of Evacetrapib Single and Multiple Doses on High Density Lipoprotein Cholesterol (HDL-C), Low Density Lipoprotein Cholesterol (LDL-C), and Triglycerides (TG) LDL-C	2.289 millimoles per liter (mmol/L) Standard Deviation 0.483	1.241 millimoles per liter (mmol/L) Standard Deviation 0.574
Effect of Evacetrapib Single and Multiple Doses on High Density Lipoprotein Cholesterol (HDL-C), Low Density Lipoprotein Cholesterol (LDL-C), and Triglycerides (TG) TG	0.984 millimoles per liter (mmol/L) Standard Deviation 0.312	1.221 millimoles per liter (mmol/L) Standard Deviation 0.356

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

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