Trial Outcomes & Findings for A Study of Mirikizumab in Participants With Plaque Psoriasis (NCT NCT03718884)
NCT ID: NCT03718884
Last Updated: 2024-01-29
Results Overview
Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Midazolam
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
29 participants
Primary outcome timeframe
Period 1: Day 1: predose, 0.5, 1, 2, 3, 4, 6, 8 and 12 hours, Day 2: 24 hours; Period 2: Day 116: predose, 0.5, 1, 2, 3, 4, 6, 8 and 12 hours, Day 117: 24 hours; post-dose
Results posted on
2024-01-29
Participant Flow
Participant milestones
| Measure |
Drug Cocktail
Period 1:
Participants received a single dose of the following drug cocktail on Day 1: 1 mg midazolam, 10 mg warfarin, 10 mg vitamin K, 30 mg dextromethorphan, 20 mg omeprazole, 100 mg Caffeine administered orally.
|
Mirikizumab + Drug Cocktail
Period 2:
Participants received 250 mg mirikizumab subcutaneously (SC) once every 4 weeks (Q4W) for 16 weeks (Days 1 to Day 113).
Period 2:
Participants received the second dose of the drug cocktail: 1 mg midazolam, 10 mg warfarin, 10 mg vitamin K, 30 mg dextromethorphan, 20 mg omeprazole, 100 mg caffeine administered orally on Day 116.
|
|---|---|---|
|
Period 1 (6 Days)
STARTED
|
29
|
0
|
|
Period 1 (6 Days)
Received at Least One Dose of Study Drug
|
29
|
0
|
|
Period 1 (6 Days)
COMPLETED
|
29
|
0
|
|
Period 1 (6 Days)
NOT COMPLETED
|
0
|
0
|
|
Period 2 (120 Days)
STARTED
|
0
|
29
|
|
Period 2 (120 Days)
COMPLETED
|
0
|
26
|
|
Period 2 (120 Days)
NOT COMPLETED
|
0
|
3
|
Reasons for withdrawal
| Measure |
Drug Cocktail
Period 1:
Participants received a single dose of the following drug cocktail on Day 1: 1 mg midazolam, 10 mg warfarin, 10 mg vitamin K, 30 mg dextromethorphan, 20 mg omeprazole, 100 mg Caffeine administered orally.
|
Mirikizumab + Drug Cocktail
Period 2:
Participants received 250 mg mirikizumab subcutaneously (SC) once every 4 weeks (Q4W) for 16 weeks (Days 1 to Day 113).
Period 2:
Participants received the second dose of the drug cocktail: 1 mg midazolam, 10 mg warfarin, 10 mg vitamin K, 30 mg dextromethorphan, 20 mg omeprazole, 100 mg caffeine administered orally on Day 116.
|
|---|---|---|
|
Period 2 (120 Days)
Withdrawal by Subject
|
0
|
1
|
|
Period 2 (120 Days)
Lost to Follow-up
|
0
|
2
|
Baseline Characteristics
A Study of Mirikizumab in Participants With Plaque Psoriasis
Baseline characteristics by cohort
| Measure |
All Participants
n=29 Participants
Drug Cocktail
Period 1:
Participants received a single dose of the following drug cocktail on Day 1: 1 mg midazolam, 10 mg warfarin, 10 mg vitamin K, 30 mg dextromethorphan, 20 mg omeprazole, 100 mg Caffeine administered orally.
Mirikizumab + Drug Cocktail
Period 2:
Participants received 250 mg mirikizumab subcutaneously (SC) once every 4 weeks (Q4W) for 16 weeks (Days 1 to Day 113)
Period 2:
Participants received the second dose of the drug cocktail: 1 mg midazolam, 10 mg warfarin, 10 mg vitamin K, 30 mg dextromethorphan, 20 mg omeprazole, 100 mg caffeine administered orally on Day 116.
|
|---|---|
|
Age, Continuous
|
52.1 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
5 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
24 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
11 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
18 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
|
1 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
|
4 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
24 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 States
|
29 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Period 1: Day 1: predose, 0.5, 1, 2, 3, 4, 6, 8 and 12 hours, Day 2: 24 hours; Period 2: Day 116: predose, 0.5, 1, 2, 3, 4, 6, 8 and 12 hours, Day 117: 24 hours; post-dosePopulation: All participants who received at least one dose of study drug cocktail and had evaluable PK data.
Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Midazolam
Outcome measures
| Measure |
Period 1: 1 mg Midazolam
n=29 Participants
Period 1: Participants received 1 mg midazolam administered orally on Day 1.
|
Period 2: 1 mg Midazolam
n=26 Participants
Period 2: Participants received 1 mg midazolam administered orally on day 116.
|
|---|---|---|
|
Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Midazolam
|
4.07 Nanograms per millilitre (ng/mL)
Geometric Coefficient of Variation 29
|
4.46 Nanograms per millilitre (ng/mL)
Geometric Coefficient of Variation 35
|
PRIMARY outcome
Timeframe: Period 1: Day 1: predose,1,2, 4,6, 8 and 10 hours, Day 2: 24 hours, Day 3: 48 hours, Day 4: 72 hours, Day 5: 96 hours; Period 2: Day 116: predose,1,2,4,6,8 and 10 hours, Day 117: 24 hours, Day 118: 48 hours, Day 119: 72 hours, Day 120: 96 hours;post-dosePopulation: All participants who received at least one dose of study drug cocktail and had evaluable PK data.
PK: Cmax of Warfarin
Outcome measures
| Measure |
Period 1: 1 mg Midazolam
n=29 Participants
Period 1: Participants received 1 mg midazolam administered orally on Day 1.
|
Period 2: 1 mg Midazolam
n=26 Participants
Period 2: Participants received 1 mg midazolam administered orally on day 116.
|
|---|---|---|
|
PK: Cmax of Warfarin
|
543 ng/mL
Geometric Coefficient of Variation 18
|
506 ng/mL
Geometric Coefficient of Variation 23
|
PRIMARY outcome
Timeframe: Period 1: Day 1: predose, 1, 2, 4, 6, 8 and 10 hours, Day 2: 24 hours, Day 3: 48 hours, Day 4: 72 hours; Period 2: Day 116: predose, 1, 2,4, 6, 8 and 10 hours, Day 117: 24 hours, Day 118: 48 hours, Day 119: 72 hours;post-dosePopulation: All participants who received at least one dose of study drug cocktail and had evaluable PK data.
PK: Cmax of Dextromethorphan
Outcome measures
| Measure |
Period 1: 1 mg Midazolam
n=29 Participants
Period 1: Participants received 1 mg midazolam administered orally on Day 1.
|
Period 2: 1 mg Midazolam
n=26 Participants
Period 2: Participants received 1 mg midazolam administered orally on day 116.
|
|---|---|---|
|
PK: Cmax of Dextromethorphan
|
1.60 ng/mL
Geometric Coefficient of Variation 154
|
1.47 ng/mL
Geometric Coefficient of Variation 118
|
PRIMARY outcome
Timeframe: Period 1: Day 1: predose, 0.5, 1, 2, 3, 4, 6, 8 and 12 hours, Day 2: 24 hours, Day 3: 48 hours; Period 2: Day 116: predose, 0.5, 1, 2, 3, 4, 6, 8 and 12 hours, Day 117: 24 hours, Day 118: 48 hours;post-dosePopulation: All participants who received at least one dose of study drug cocktail and had evaluable PK data.
PK: Cmax of Omeprazole
Outcome measures
| Measure |
Period 1: 1 mg Midazolam
n=29 Participants
Period 1: Participants received 1 mg midazolam administered orally on Day 1.
|
Period 2: 1 mg Midazolam
n=26 Participants
Period 2: Participants received 1 mg midazolam administered orally on day 116.
|
|---|---|---|
|
PK: Cmax of Omeprazole
|
369 ng/mL
Geometric Coefficient of Variation 137
|
437 ng/mL
Geometric Coefficient of Variation 81
|
PRIMARY outcome
Timeframe: Period 1: Day 1: predose, 0.5, 1, 2, 3, 4, 6, 8 and 12 hours, Day 2: 24 hours, Day 3: 48 hours; Period 2: Day 116: predose, 0.5, 1, 2, 3, 4, 6, 8 and 12 hours, Day 117: 24 hours, Day 118: 48 hours;post-dosePopulation: All participants who received at least one dose of study drug cocktail and had evaluable PK data.
PK: Cmax of Caffeine
Outcome measures
| Measure |
Period 1: 1 mg Midazolam
n=26 Participants
Period 1: Participants received 1 mg midazolam administered orally on Day 1.
|
Period 2: 1 mg Midazolam
n=18 Participants
Period 2: Participants received 1 mg midazolam administered orally on day 116.
|
|---|---|---|
|
PK: Cmax of Caffeine
|
2400 ng/mL
Geometric Coefficient of Variation 19
|
2340 ng/mL
Geometric Coefficient of Variation 26
|
PRIMARY outcome
Timeframe: Period 1: Day 1: predose, 0.5, 1, 2, 3, 4, 6, 8 and 12 hours, Day 2: 24 hours; Period 2: Day 116: predose, 0.5, 1, 2, 3, 4, 6, 8 and 12 hours, Day 117: 24 hours;post-dosePopulation: All participants who received at least one dose of study drug cocktail and had evaluable PK data.
PK: Area Under the Concentration Curve (AUC) Time Zero to Infinity (AUC \[0-∞\]) of Midazolam
Outcome measures
| Measure |
Period 1: 1 mg Midazolam
n=29 Participants
Period 1: Participants received 1 mg midazolam administered orally on Day 1.
|
Period 2: 1 mg Midazolam
n=26 Participants
Period 2: Participants received 1 mg midazolam administered orally on day 116.
|
|---|---|---|
|
PK: Area Under the Concentration Curve (AUC) Time Zero to Infinity (AUC [0-∞]) of Midazolam
|
13.4 Nanograms hour per millilitre (ng*h/mL)
Geometric Coefficient of Variation 43
|
15.6 Nanograms hour per millilitre (ng*h/mL)
Geometric Coefficient of Variation 40
|
PRIMARY outcome
Timeframe: Period 1: Day 1: predose,1,2,4,6,8 and 10 hours, Day 2: 24 hours, Day 3: 48 hours, Day 4: 72 hours, Day 5: 96 hours; Period 2: Day 116: predose, 1, 2, 4, 6, 8 and 10 hours, Day 117: 24 hours, Day 118: 48 hours,Day 119: 72 hours,Day 120: 96 hours;post-dosePopulation: All participants who received at least one dose of study drug cocktail and had evaluable PK data.
PK: AUC Time Zero to Infinity (AUC\[0-∞\]) of Warfarin
Outcome measures
| Measure |
Period 1: 1 mg Midazolam
n=28 Participants
Period 1: Participants received 1 mg midazolam administered orally on Day 1.
|
Period 2: 1 mg Midazolam
n=25 Participants
Period 2: Participants received 1 mg midazolam administered orally on day 116.
|
|---|---|---|
|
PK: AUC Time Zero to Infinity (AUC[0-∞]) of Warfarin
|
14800 ng*h/mL
Geometric Coefficient of Variation 34
|
13800 ng*h/mL
Geometric Coefficient of Variation 31
|
PRIMARY outcome
Timeframe: Period 1: Day 1: predose,1,2,4,6,8 and 10 hours, Day 2: 24 hours, Day 3: 48 hours, Day 4: 72 hours; Period 2: Day 116: predose, 1, 2,4, 6, 8 and 10 hours, Day 117: 24 hours, Day 118: 48 hours, Day 119: 72 hours;post-dosePopulation: All participants who received at least one dose of study drug cocktail and had evaluable PK data.
PK: AUC Time Zero to Infinity (AUC\[0-∞\]) of Dextromethorphan
Outcome measures
| Measure |
Period 1: 1 mg Midazolam
n=29 Participants
Period 1: Participants received 1 mg midazolam administered orally on Day 1.
|
Period 2: 1 mg Midazolam
n=26 Participants
Period 2: Participants received 1 mg midazolam administered orally on day 116.
|
|---|---|---|
|
PK: AUC Time Zero to Infinity (AUC[0-∞]) of Dextromethorphan
|
14.6 ng*h/mL
Geometric Coefficient of Variation 160
|
13.0 ng*h/mL
Geometric Coefficient of Variation 132
|
PRIMARY outcome
Timeframe: Period 1: Day 1: predose, 0.5, 1, 2, 3, 4, 6, 8 and 12 hours, Day 2: 24 hours, Day 3: 48 hours; Period 2: Day 116: predose, 0.5, 1, 2, 3, 4, 6, 8 and 12 hours, Day 117: 24 hours, Day 118: 48 hours;post-dosePopulation: All participants who received at least one dose of study drug cocktail and had evaluable PK data.
PK: AUC Time Zero to Infinity (AUC\[0-∞\]) of Omeprazole
Outcome measures
| Measure |
Period 1: 1 mg Midazolam
n=20 Participants
Period 1: Participants received 1 mg midazolam administered orally on Day 1.
|
Period 2: 1 mg Midazolam
n=20 Participants
Period 2: Participants received 1 mg midazolam administered orally on day 116.
|
|---|---|---|
|
PK: AUC Time Zero to Infinity (AUC[0-∞]) of Omeprazole
|
1280 ng*h/mL
Geometric Coefficient of Variation 142
|
1530 ng*h/mL
Geometric Coefficient of Variation 103
|
PRIMARY outcome
Timeframe: Period 1: Day 1: predose, 0.5, 1, 2, 3, 4, 6, 8 and 12 hours, Day 2: 24 hours, Day 3: 48 hours; Period 2: Day 116: predose, 0.5, 1, 2, 3, 4, 6, 8 and 12 hours, Day 117: 24 hours, Day 118: 48 hours;post-dosePopulation: All participants who received at least one dose of study drug cocktail and had evaluable PK data.
PK: AUC Time Zero to Infinity (AUC\[0-∞\]) of Caffeine
Outcome measures
| Measure |
Period 1: 1 mg Midazolam
n=24 Participants
Period 1: Participants received 1 mg midazolam administered orally on Day 1.
|
Period 2: 1 mg Midazolam
n=18 Participants
Period 2: Participants received 1 mg midazolam administered orally on day 116.
|
|---|---|---|
|
PK: AUC Time Zero to Infinity (AUC[0-∞]) of Caffeine
|
19700 ng*h/mL
Geometric Coefficient of Variation 46
|
20800 ng*h/mL
Geometric Coefficient of Variation 48
|
Adverse Events
Period 1: Drug Cocktail
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Period 2: Mirikizumab
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Period 2: Drug Cocktail
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 |
Period 1: Drug Cocktail
n=29 participants at risk
Period 1:
Participants received a single dose of the following drug cocktail on Day 1: 1 mg midazolam, 10 mg warfarin, 10 mg vitamin K, 30 mg dextromethorphan, 20 mg omeprazole, 100 mg Caffeine administered orally.
|
Period 2: Mirikizumab
n=29 participants at risk
Period 2:
Participants received 250 mg mirikizumab subcutaneously (SC) once every 4 weeks (Q4W) for 16 weeks (Days 1 to Day 113).
|
Period 2: Drug Cocktail
n=29 participants at risk
Period 2:
Participants received the second dose of the drug cocktail: 1 mg midazolam, 10 mg warfarin, 10 mg vitamin K, 30 mg dextromethorphan, 20 mg omeprazole, 100 mg caffeine administered orally on Day 116.
|
|---|---|---|---|
|
Injury, poisoning and procedural complications
Hand fracture
|
0.00%
0/29 • Baseline Up To 144 Days
All Participants who received at least one dose of study drug.
|
6.9%
2/29 • Number of events 3 • Baseline Up To 144 Days
All Participants who received at least one dose of study drug.
|
0.00%
0/29 • Baseline Up To 144 Days
All Participants who received at least one dose of study drug.
|
|
Injury, poisoning and procedural complications
Limb injury
|
0.00%
0/29 • Baseline Up To 144 Days
All Participants who received at least one dose of study drug.
|
6.9%
2/29 • Number of events 2 • Baseline Up To 144 Days
All Participants who received at least one dose of study drug.
|
0.00%
0/29 • Baseline Up To 144 Days
All Participants who received at least one dose of study drug.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60