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A Study of Mirikizumab in Participants With Plaque Psoriasis

Evaluation of the Effect of Mirikizumab on the Pharmacokinetics of Cytochrome P450 Substrates in Patients With Moderate-to-Severe Plaque Psoriasis

Status
Completed
Phases
Phase 1
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT03718884
Enrollment
29
Registered
2018-10-25
Start date
2018-10-23
Completion date
2019-10-28
Last updated
2024-01-29

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Psoriasis

Brief summary

This study is known as a drug interaction study. The purpose is to learn how commonly used drugs or substances (midazolam, warfarin, dextromethorphan, omeprazole, and caffeine) and their breakdown products get into the bloodstream after taking a cocktail (combination) of them before and after multiple doses of mirikizumab. The study will last about 23 weeks for each participant. Screening must be completed within 4 weeks prior to study start.

Interventions

DRUGDrug Cocktail

Drug cocktail consists of caffeine, warfarin plus vitamin K, omeprazole, dextromethorphan, and midazolam, administered orally

DRUGMirikizumab

Administered SC

Sponsors

Eli Lilly and Company
Lead SponsorINDUSTRY

Study design

Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
BASIC_SCIENCE
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No

Inclusion criteria

* Males and females with chronic plaque psoriasis for at least 6 months who are candidates for systemic therapy or phototherapy * Have greater than or equal to (≥) 10 percent body surface area (BSA) involvement at screening and first admission to the clinical site

Exclusion criteria

* Pregnant or nursing (lactating) * History of an ongoing, chronic or recurrent infectious disease, or evidence of tuberculosis infection * Have major surgery within 8 weeks prior to first admission to the clinical site or during the study * Have a history of lymphoma, leukemia, or any malignancy * Require treatment with the cocktail drugs within 14 days prior to the first administration of the drug cocktail through the end of Week 12 assessments * Have participated in any other study with mirikizumab

Design outcomes

Primary

MeasureTime frameDescription
Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of MidazolamPeriod 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-dosePharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Midazolam
PK: Cmax of WarfarinPeriod 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-dosePK: Cmax of Warfarin
PK: Cmax of DextromethorphanPeriod 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-dosePK: Cmax of Dextromethorphan
PK: Cmax of OmeprazolePeriod 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-dosePK: Cmax of Omeprazole
PK: Cmax of CaffeinePeriod 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-dosePK: Cmax of Caffeine
PK: Area Under the Concentration Curve (AUC) Time Zero to Infinity (AUC [0-∞]) of MidazolamPeriod 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-dosePK: Area Under the Concentration Curve (AUC) Time Zero to Infinity (AUC \[0-∞\]) of Midazolam
PK: AUC Time Zero to Infinity (AUC[0-∞]) of WarfarinPeriod 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-dosePK: AUC Time Zero to Infinity (AUC\[0-∞\]) of Warfarin
PK: AUC Time Zero to Infinity (AUC[0-∞]) of DextromethorphanPeriod 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-dosePK: AUC Time Zero to Infinity (AUC\[0-∞\]) of Dextromethorphan
PK: AUC Time Zero to Infinity (AUC[0-∞]) of OmeprazolePeriod 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-dosePK: AUC Time Zero to Infinity (AUC\[0-∞\]) of Omeprazole
PK: AUC Time Zero to Infinity (AUC[0-∞]) of CaffeinePeriod 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-dosePK: AUC Time Zero to Infinity (AUC\[0-∞\]) of Caffeine

Countries

United States

Participant flow

Participants by arm

ArmCount
All 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.
29
Total29

Withdrawals & dropouts

PeriodReasonFG000FG001
Period 2 (120 Days)Lost to Follow-up02
Period 2 (120 Days)Withdrawal by Subject01

Baseline characteristics

CharacteristicAll Participants
Age, Continuous52.1 years
Ethnicity (NIH/OMB)
Hispanic or Latino
11 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
18 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
Race (NIH/OMB)
Asian
1 Participants
Race (NIH/OMB)
Black or African American
4 Participants
Race (NIH/OMB)
More than one race
0 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants
Race (NIH/OMB)
White
24 Participants
Region of Enrollment
United States
29 Participants
Sex: Female, Male
Female
5 Participants
Sex: Female, Male
Male
24 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
EG002
affected / at risk
deaths
Total, all-cause mortality
0 / 290 / 290 / 29
other
Total, other adverse events
0 / 293 / 290 / 29
serious
Total, serious adverse events
0 / 290 / 290 / 29

Outcome results

Primary

Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Midazolam

Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Midazolam

Time frame: 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

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

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
Period 1: 1 mg MidazolamPharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Midazolam4.07 Nanograms per millilitre (ng/mL)Geometric Coefficient of Variation 29
Period 2: 1 mg MidazolamPharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Midazolam4.46 Nanograms per millilitre (ng/mL)Geometric Coefficient of Variation 35
Primary

PK: Area Under the Concentration Curve (AUC) Time Zero to Infinity (AUC [0-∞]) of Midazolam

PK: Area Under the Concentration Curve (AUC) Time Zero to Infinity (AUC \[0-∞\]) of Midazolam

Time frame: 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

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

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
Period 1: 1 mg MidazolamPK: Area Under the Concentration Curve (AUC) Time Zero to Infinity (AUC [0-∞]) of Midazolam13.4 Nanograms hour per millilitre (ng*h/mL)Geometric Coefficient of Variation 43
Period 2: 1 mg MidazolamPK: Area Under the Concentration Curve (AUC) Time Zero to Infinity (AUC [0-∞]) of Midazolam15.6 Nanograms hour per millilitre (ng*h/mL)Geometric Coefficient of Variation 40
Primary

PK: AUC Time Zero to Infinity (AUC[0-∞]) of Caffeine

PK: AUC Time Zero to Infinity (AUC\[0-∞\]) of Caffeine

Time frame: 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-dose

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

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
Period 1: 1 mg MidazolamPK: AUC Time Zero to Infinity (AUC[0-∞]) of Caffeine19700 ng*h/mLGeometric Coefficient of Variation 46
Period 2: 1 mg MidazolamPK: AUC Time Zero to Infinity (AUC[0-∞]) of Caffeine20800 ng*h/mLGeometric Coefficient of Variation 48
Primary

PK: AUC Time Zero to Infinity (AUC[0-∞]) of Dextromethorphan

PK: AUC Time Zero to Infinity (AUC\[0-∞\]) of Dextromethorphan

Time frame: 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-dose

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

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
Period 1: 1 mg MidazolamPK: AUC Time Zero to Infinity (AUC[0-∞]) of Dextromethorphan14.6 ng*h/mLGeometric Coefficient of Variation 160
Period 2: 1 mg MidazolamPK: AUC Time Zero to Infinity (AUC[0-∞]) of Dextromethorphan13.0 ng*h/mLGeometric Coefficient of Variation 132
Primary

PK: AUC Time Zero to Infinity (AUC[0-∞]) of Omeprazole

PK: AUC Time Zero to Infinity (AUC\[0-∞\]) of Omeprazole

Time frame: 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-dose

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

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
Period 1: 1 mg MidazolamPK: AUC Time Zero to Infinity (AUC[0-∞]) of Omeprazole1280 ng*h/mLGeometric Coefficient of Variation 142
Period 2: 1 mg MidazolamPK: AUC Time Zero to Infinity (AUC[0-∞]) of Omeprazole1530 ng*h/mLGeometric Coefficient of Variation 103
Primary

PK: AUC Time Zero to Infinity (AUC[0-∞]) of Warfarin

PK: AUC Time Zero to Infinity (AUC\[0-∞\]) of Warfarin

Time frame: 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-dose

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

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
Period 1: 1 mg MidazolamPK: AUC Time Zero to Infinity (AUC[0-∞]) of Warfarin14800 ng*h/mLGeometric Coefficient of Variation 34
Period 2: 1 mg MidazolamPK: AUC Time Zero to Infinity (AUC[0-∞]) of Warfarin13800 ng*h/mLGeometric Coefficient of Variation 31
Primary

PK: Cmax of Caffeine

PK: Cmax of Caffeine

Time frame: 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-dose

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

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
Period 1: 1 mg MidazolamPK: Cmax of Caffeine2400 ng/mLGeometric Coefficient of Variation 19
Period 2: 1 mg MidazolamPK: Cmax of Caffeine2340 ng/mLGeometric Coefficient of Variation 26
Primary

PK: Cmax of Dextromethorphan

PK: Cmax of Dextromethorphan

Time frame: 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-dose

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

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
Period 1: 1 mg MidazolamPK: Cmax of Dextromethorphan1.60 ng/mLGeometric Coefficient of Variation 154
Period 2: 1 mg MidazolamPK: Cmax of Dextromethorphan1.47 ng/mLGeometric Coefficient of Variation 118
Primary

PK: Cmax of Omeprazole

PK: Cmax of Omeprazole

Time frame: 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-dose

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

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
Period 1: 1 mg MidazolamPK: Cmax of Omeprazole369 ng/mLGeometric Coefficient of Variation 137
Period 2: 1 mg MidazolamPK: Cmax of Omeprazole437 ng/mLGeometric Coefficient of Variation 81
Primary

PK: Cmax of Warfarin

PK: Cmax of Warfarin

Time frame: 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-dose

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

ArmMeasureValue (GEOMETRIC_MEAN)Dispersion
Period 1: 1 mg MidazolamPK: Cmax of Warfarin543 ng/mLGeometric Coefficient of Variation 18
Period 2: 1 mg MidazolamPK: Cmax of Warfarin506 ng/mLGeometric Coefficient of Variation 23

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026