Trial Outcomes & Findings for A Study of Evacetrapib in Healthy Participants (NCT NCT01736254)
NCT ID: NCT01736254
Last Updated: 2018-10-03
Results Overview
Venous blood samples were taken on Day 11 for PK parameter estimates of evacetrapib alone and on Day 22 for PK parameter estimates of evacetrapib when coadministered with gemfibrozil.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
24 participants
Primary outcome timeframe
Predose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose on Day 11 and Day 22
Results posted on
2018-10-03
Participant Flow
Participant milestones
| Measure |
All Participants
All participants were assigned to the following treatment regimen:
Period 1: Single oral dose of 600 milligrams (mg) gemfibrozil in the morning of Day 1.
Period 2: Oral doses of 130 mg evacetrapib once a day (QD) for 11 days (Days 2 to 12).
Period 3: Oral doses of 600 mg gemfibrozil twice a day (BID) and 130 mg evacetrapib QD for 10 days (Days 13 to 22), with a single dose of 600 mg gemfibrozil on Day 23.
|
|---|---|
|
Period 1 (Day 1)
STARTED
|
24
|
|
Period 1 (Day 1)
Received at Least One Dose of Study Drug
|
24
|
|
Period 1 (Day 1)
COMPLETED
|
24
|
|
Period 1 (Day 1)
NOT COMPLETED
|
0
|
|
Period 2 (Days 2 to 12)
STARTED
|
24
|
|
Period 2 (Days 2 to 12)
COMPLETED
|
21
|
|
Period 2 (Days 2 to 12)
NOT COMPLETED
|
3
|
|
Period 3 (Days 13 to 23)
STARTED
|
21
|
|
Period 3 (Days 13 to 23)
COMPLETED
|
20
|
|
Period 3 (Days 13 to 23)
NOT COMPLETED
|
1
|
Reasons for withdrawal
| Measure |
All Participants
All participants were assigned to the following treatment regimen:
Period 1: Single oral dose of 600 milligrams (mg) gemfibrozil in the morning of Day 1.
Period 2: Oral doses of 130 mg evacetrapib once a day (QD) for 11 days (Days 2 to 12).
Period 3: Oral doses of 600 mg gemfibrozil twice a day (BID) and 130 mg evacetrapib QD for 10 days (Days 13 to 22), with a single dose of 600 mg gemfibrozil on Day 23.
|
|---|---|
|
Period 2 (Days 2 to 12)
Adverse Event
|
3
|
|
Period 3 (Days 13 to 23)
Adverse Event
|
1
|
Baseline Characteristics
A Study of Evacetrapib in Healthy Participants
Baseline characteristics by cohort
| Measure |
All Participants
n=24 Participants
All participants were assigned to the following treatment regimen:
Period 1: Single oral dose of 600 mg gemfibrozil in the morning of Day 1.
Period 2: Oral doses of 130 mg evacetrapib QD for 11 days (Days 2 to 12).
Period 3: Oral doses of 600 mg gemfibrozil BID and 130 mg evacetrapib QD for 10 days (Days 13 to 22), with a single dose of 600 mg gemfibrozil on Day 23.
|
|---|---|
|
Age, Continuous
|
41.8 years
STANDARD_DEVIATION 10.4 • n=5 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
22 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
14 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black
|
7 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Multiple
|
3 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
24 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Predose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose on Day 11 and Day 22Population: All participants who received at least 1 dose of evacetrapib or gemfibrozil and had evaluable Cmax data.
Venous blood samples were taken on Day 11 for PK parameter estimates of evacetrapib alone and on Day 22 for PK parameter estimates of evacetrapib when coadministered with gemfibrozil.
Outcome measures
| Measure |
Evacetrapib
n=22 Participants
Oral doses of 130 mg evacetrapib QD for 10 days (Day 2 through Day 12).
|
Evacetrapib + Gemfibrozil
n=20 Participants
Oral doses of 600 mg gemfibrozil BID and 130 mg evacetrapib QD for 10 days (Day 13 through Day 22). Single oral dose of 600 mg gemfibrozil on Day 23.
|
|---|---|---|
|
Pharmacokinetics (PK): Maximum Concentration (Cmax) of Evacetrapib
|
1270 nanograms/milliliter (ng/mL)
Geometric Coefficient of Variation 26
|
1290 nanograms/milliliter (ng/mL)
Geometric Coefficient of Variation 26
|
PRIMARY outcome
Timeframe: Predose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose on Day 11 and Day 22Population: All participants who received at least 1 dose of evacetrapib or gemfibrozil and had evaluable AUCτ data.
Venous blood samples were taken on Day 11 for PK parameter estimates of evacetrapib alone and on Day 22 for PK parameter estimates of evacetrapib when coadministered with gemfibrozil.
Outcome measures
| Measure |
Evacetrapib
n=22 Participants
Oral doses of 130 mg evacetrapib QD for 10 days (Day 2 through Day 12).
|
Evacetrapib + Gemfibrozil
n=19 Participants
Oral doses of 600 mg gemfibrozil BID and 130 mg evacetrapib QD for 10 days (Day 13 through Day 22). Single oral dose of 600 mg gemfibrozil on Day 23.
|
|---|---|---|
|
Pharmacokinetics (PK): Area Under the Concentration Curve Over a 24 Hour Dosing Interval (AUCτ) of Evacetrapib
|
11300 nanograms*hours/milliliter (ng*h/mL)
Geometric Coefficient of Variation 20
|
11400 nanograms*hours/milliliter (ng*h/mL)
Geometric Coefficient of Variation 21
|
PRIMARY outcome
Timeframe: Predose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose on Day 11 and Day 22Population: All participants who received at least 1 dose of evacetrapib or gemfibrozil and had evaluable Tmax data.
Venous blood samples were taken on Day 11 for PK parameter estimates of evacetrapib alone and on Day 22 for PK parameter estimates of evacetrapib when coadministered with gemfibrozil.
Outcome measures
| Measure |
Evacetrapib
n=22 Participants
Oral doses of 130 mg evacetrapib QD for 10 days (Day 2 through Day 12).
|
Evacetrapib + Gemfibrozil
n=20 Participants
Oral doses of 600 mg gemfibrozil BID and 130 mg evacetrapib QD for 10 days (Day 13 through Day 22). Single oral dose of 600 mg gemfibrozil on Day 23.
|
|---|---|---|
|
Pharmacokinetics (PK): Time of Maximum Observed Drug Concentration (Tmax) of Evacetrapib
|
4.00 hours
Interval 2.02 to 6.0
|
3.00 hours
Interval 2.0 to 4.0
|
SECONDARY outcome
Timeframe: Predose and 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hours postdose on Day 1 and Day 13Population: All participants who received at least 1 dose of evacetrapib or gemfibrozil and had evaluable AUCτ data.
Venous blood samples were taken on Day 1 for PK parameter estimates of gemfibrozil alone and on Day 13 for PK parameter estimates of gemfibrozil when coadministered with evacetrapib.
Outcome measures
| Measure |
Evacetrapib
n=24 Participants
Oral doses of 130 mg evacetrapib QD for 10 days (Day 2 through Day 12).
|
Evacetrapib + Gemfibrozil
n=21 Participants
Oral doses of 600 mg gemfibrozil BID and 130 mg evacetrapib QD for 10 days (Day 13 through Day 22). Single oral dose of 600 mg gemfibrozil on Day 23.
|
|---|---|---|
|
Pharmacokinetics (PK): Area Under the Concentration Curve Over a 12 Hour Dosing Interval (AUCτ) of Gemfibrozil
|
55700 ng*h/mL
Geometric Coefficient of Variation 23
|
53800 ng*h/mL
Geometric Coefficient of Variation 22
|
SECONDARY outcome
Timeframe: Predose and 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hours postdose on Day 1 and Day 13Population: All participants who received at least 1 dose of evacetrapib or gemfibrozil and had evaluable Cmax data.
Venous blood samples were taken on Day 1 for PK parameter estimates of gemfibrozil alone and on Day 13 for PK parameter estimates of gemfibrozil when coadministered with evacetrapib.
Outcome measures
| Measure |
Evacetrapib
n=24 Participants
Oral doses of 130 mg evacetrapib QD for 10 days (Day 2 through Day 12).
|
Evacetrapib + Gemfibrozil
n=21 Participants
Oral doses of 600 mg gemfibrozil BID and 130 mg evacetrapib QD for 10 days (Day 13 through Day 22). Single oral dose of 600 mg gemfibrozil on Day 23.
|
|---|---|---|
|
Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Gemfibrozil
|
17400 ng/mL
Geometric Coefficient of Variation 32
|
16800 ng/mL
Geometric Coefficient of Variation 34
|
SECONDARY outcome
Timeframe: Predose and 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hours postdose on Day 1 and Day 13Population: All participants who received at least 1 dose of evacetrapib or gemfibrozil and had evaluable Tmax data.
Venous blood samples were taken on Day 1 for PK parameter estimates of gemfibrozil alone and on Day 13 for PK parameter estimates of gemfibrozil when coadministered with evacetrapib.
Outcome measures
| Measure |
Evacetrapib
n=24 Participants
Oral doses of 130 mg evacetrapib QD for 10 days (Day 2 through Day 12).
|
Evacetrapib + Gemfibrozil
n=21 Participants
Oral doses of 600 mg gemfibrozil BID and 130 mg evacetrapib QD for 10 days (Day 13 through Day 22). Single oral dose of 600 mg gemfibrozil on Day 23.
|
|---|---|---|
|
Pharmacokinetics (PK): Time of Maximum Observed Drug Concentration (Tmax) of Gemfibrozil
|
1.00 hours
Interval 1.0 to 4.0
|
1.08 hours
Interval 1.08 to 4.0
|
Adverse Events
Gemfibrozil
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Evacetrapib
Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths
Evacetrapib + Gemfibrozil
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 |
Gemfibrozil
n=24 participants at risk
Single oral dose of 600 mg gemfibrozil on Day 1.
|
Evacetrapib
n=24 participants at risk
Oral doses of 130 mg evacetrapib QD for 10 days (Day 2 through Day 12).
|
Evacetrapib + Gemfibrozil
n=21 participants at risk
Oral doses of 600 mg gemfibrozil BID and 130 mg evacetrapib QD for 10 days (Day 13 through Day 22). Single oral dose of 600 mg gemfibrozil on Day 23.
|
|---|---|---|---|
|
Eye disorders
Lacrimation increased
|
0.00%
0/24
|
4.2%
1/24 • Number of events 1
|
0.00%
0/21
|
|
Eye disorders
Ocular hyperaemia
|
0.00%
0/24
|
0.00%
0/24
|
4.8%
1/21 • Number of events 1
|
|
Gastrointestinal disorders
Bowel movement irregularity
|
0.00%
0/24
|
4.2%
1/24 • Number of events 1
|
0.00%
0/21
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/24
|
0.00%
0/24
|
4.8%
1/21 • Number of events 1
|
|
Gastrointestinal disorders
Flatulence
|
0.00%
0/24
|
4.2%
1/24 • Number of events 1
|
0.00%
0/21
|
|
Gastrointestinal disorders
Glossitis
|
0.00%
0/24
|
4.2%
1/24 • Number of events 1
|
0.00%
0/21
|
|
Gastrointestinal disorders
Tongue disorder
|
0.00%
0/24
|
4.2%
1/24 • Number of events 1
|
0.00%
0/21
|
|
Gastrointestinal disorders
Toothache
|
0.00%
0/24
|
4.2%
1/24 • Number of events 1
|
0.00%
0/21
|
|
Infections and infestations
Hordeolum
|
0.00%
0/24
|
4.2%
1/24 • Number of events 1
|
0.00%
0/21
|
|
Investigations
Liver function test abnormal
|
0.00%
0/24
|
4.2%
1/24 • Number of events 1
|
0.00%
0/21
|
|
Metabolism and nutrition disorders
Decreased appetite
|
0.00%
0/24
|
0.00%
0/24
|
4.8%
1/21 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/24
|
0.00%
0/24
|
9.5%
2/21 • Number of events 2
|
|
Nervous system disorders
Headache
|
0.00%
0/24
|
0.00%
0/24
|
4.8%
1/21 • Number of events 1
|
|
Psychiatric disorders
Insomnia
|
0.00%
0/24
|
4.2%
1/24 • Number of events 1
|
0.00%
0/21
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
4.2%
1/24 • Number of events 1
|
4.2%
1/24 • Number of events 1
|
0.00%
0/21
|
|
Respiratory, thoracic and mediastinal disorders
Dry throat
|
0.00%
0/24
|
0.00%
0/24
|
4.8%
1/21 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
0.00%
0/24
|
4.2%
1/24 • Number of events 1
|
0.00%
0/21
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
0.00%
0/24
|
8.3%
2/24 • Number of events 2
|
0.00%
0/21
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary congestion
|
0.00%
0/24
|
4.2%
1/24 • Number of events 1
|
0.00%
0/21
|
|
Respiratory, thoracic and mediastinal disorders
Sneezing
|
0.00%
0/24
|
4.2%
1/24 • Number of events 1
|
0.00%
0/21
|
|
Skin and subcutaneous tissue disorders
Acne
|
0.00%
0/24
|
0.00%
0/24
|
4.8%
1/21 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/24
|
4.2%
1/24 • Number of events 1
|
4.8%
1/21 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/24
|
0.00%
0/24
|
4.8%
1/21 • Number of events 1
|
|
Vascular disorders
Flushing
|
0.00%
0/24
|
4.2%
1/24 • Number of events 1
|
0.00%
0/21
|
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