Trial Outcomes & Findings for A Study of Baricitinib and Simvastatin in Healthy Participants (NCT NCT01960140)
NCT ID: NCT01960140
Last Updated: 2017-06-06
Results Overview
The Cmax of simvastatin \[a cytochrome P450 (CYP) 3A substrate\] and its active acid metabolite (simvastatin acid) is reported.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
40 participants
Primary outcome timeframe
Period 1, Day 1 and Period 2, Day 6: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 and 48 hours postdose
Results posted on
2017-06-06
Participant Flow
This was an open-label, fixed-sequence, 2-period study of healthy participants.
Participant milestones
| Measure |
Simvastatin Then Baricitinib and Simvastatin
Period 1: 40-milligram (mg) tablet of simvastatin administered orally on Day 1.
Period 2: 10-mg dose of baricitinib (2 × 4-mg and 1 × 2-mg tablets) administered orally once daily (QD) on Days 3 through 7, with coadministration of 40-mg simvastatin tablet on Day 6.
|
|---|---|
|
Period 1 (Days 1-2)
STARTED
|
40
|
|
Period 1 (Days 1-2)
Received Simvastatin
|
40
|
|
Period 1 (Days 1-2)
COMPLETED
|
40
|
|
Period 1 (Days 1-2)
NOT COMPLETED
|
0
|
|
Period 2 (Days 3-18)
STARTED
|
40
|
|
Period 2 (Days 3-18)
Received At Least 1 Dose of Baricitinib
|
40
|
|
Period 2 (Days 3-18)
Received Simvastatin
|
38
|
|
Period 2 (Days 3-18)
COMPLETED
|
38
|
|
Period 2 (Days 3-18)
NOT COMPLETED
|
2
|
Reasons for withdrawal
| Measure |
Simvastatin Then Baricitinib and Simvastatin
Period 1: 40-milligram (mg) tablet of simvastatin administered orally on Day 1.
Period 2: 10-mg dose of baricitinib (2 × 4-mg and 1 × 2-mg tablets) administered orally once daily (QD) on Days 3 through 7, with coadministration of 40-mg simvastatin tablet on Day 6.
|
|---|---|
|
Period 2 (Days 3-18)
Adverse Event
|
2
|
Baseline Characteristics
A Study of Baricitinib and Simvastatin in Healthy Participants
Baseline characteristics by cohort
| Measure |
Simvastatin Then Baricitinib and Simvastatin
n=40 Participants
Period 1: 40-mg tablet of simvastatin administered orally on Day 1.
Period 2: 10-mg dose of baricitinib (2 × 4-mg and 1 × 2-mg tablets) administered orally QD on Days 3 through 7, with coadministration of 40-mg simvastatin tablet on Day 6.
|
|---|---|
|
Age, Continuous
|
40.0 years
STANDARD_DEVIATION 13.0 • n=5 Participants
|
|
Sex: Female, Male
Female
|
5 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
35 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
40 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
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
39 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United Kingdom
|
40 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Period 1, Day 1 and Period 2, Day 6: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 and 48 hours postdosePopulation: Participants who received study drug (simvastatin in Period 1 and at least 1 dose of baricitinib and simvastatin in Period 2) and had evaluable PK data.
The Cmax of simvastatin \[a cytochrome P450 (CYP) 3A substrate\] and its active acid metabolite (simvastatin acid) is reported.
Outcome measures
| Measure |
Simvastatin
n=40 Participants
Period 1: 40-mg tablet of simvastatin administered orally on Day 1.
|
Baricitinib and Simvastatin
n=38 Participants
Period 2: 10-mg dose of baricitinib (2 × 4-mg and 1 × 2-mg tablets) administered orally QD on Days 3 through 7, with coadministration of 40-mg simvastatin tablet on Day 6.
|
|---|---|---|
|
Pharmacokinetics (PK): Maximum Concentration (Cmax) of Simvastatin and Simvastatin Acid
Simvastatin
|
6.85 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 74
|
4.65 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 57
|
|
Pharmacokinetics (PK): Maximum Concentration (Cmax) of Simvastatin and Simvastatin Acid
Simvastatin Acid
|
1.93 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 68
|
1.60 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 50
|
PRIMARY outcome
Timeframe: Period 1, Day 1 and Period 2, Day 6: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 and 48 hours postdosePopulation: Participants who received study drug (simvastatin in Period 1 and at least 1 dose of baricitinib and simvastatin in Period 2) and had evaluable PK data.
The AUC(0-∞) of simvastatin (a CYP3A substrate) and its active acid metabolite (simvastatin acid) is reported.
Outcome measures
| Measure |
Simvastatin
n=39 Participants
Period 1: 40-mg tablet of simvastatin administered orally on Day 1.
|
Baricitinib and Simvastatin
n=36 Participants
Period 2: 10-mg dose of baricitinib (2 × 4-mg and 1 × 2-mg tablets) administered orally QD on Days 3 through 7, with coadministration of 40-mg simvastatin tablet on Day 6.
|
|---|---|---|
|
PK: Area Under the Concentration Versus Time Curve From Zero to Infinity [AUC(0-∞)] of Simvastatin and Simvastatin Acid
Simvastatin (n=39, 36)
|
40.7 nanograms*hour/milliliter (ng*h/mL)
Geometric Coefficient of Variation 86
|
33.7 nanograms*hour/milliliter (ng*h/mL)
Geometric Coefficient of Variation 75
|
|
PK: Area Under the Concentration Versus Time Curve From Zero to Infinity [AUC(0-∞)] of Simvastatin and Simvastatin Acid
Simvastatin Acid (n=33, 32)
|
26.4 nanograms*hour/milliliter (ng*h/mL)
Geometric Coefficient of Variation 81
|
21.0 nanograms*hour/milliliter (ng*h/mL)
Geometric Coefficient of Variation 64
|
Adverse Events
Simvastatin
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Baricitinib
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Baricitinib and Simvastatin
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Simvastatin
n=40 participants at risk
A 40-mg tablet of simvastatin administered orally on Day 1.
Adverse events (AEs) are reported from baseline through predose on Day 3.
|
Baricitinib
n=40 participants at risk
A 10-mg dose of baricitinib (2 × 4-mg and 1 × 2-mg tablets) administered orally QD on Days 3 through 5.
AEs are reported postdose on Day 3 through predose on Day 6.
|
Baricitinib and Simvastatin
n=38 participants at risk
A 10-mg dose of baricitinib (2 × 4-mg and 1 × 2-mg tablets) administered orally QD on Days 6 and 7, with coadministration of 40-mg simvastatin tablet on Day 6.
AEs are reported postdose on Day 6 up to Day 18.
|
|---|---|---|---|
|
Infections and infestations
Nasopharyngitis
|
0.00%
0/40 • Baseline through study completion (up to Day 18)
|
0.00%
0/40 • Baseline through study completion (up to Day 18)
|
5.3%
2/38 • Number of events 2 • Baseline through study completion (up to Day 18)
|
|
Nervous system disorders
Headache
|
7.5%
3/40 • Number of events 4 • Baseline through study completion (up to Day 18)
|
2.5%
1/40 • Number of events 1 • Baseline through study completion (up to Day 18)
|
2.6%
1/38 • Number of events 1 • Baseline through study completion (up to Day 18)
|
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