A Study of Mirikizumab in Participants With Plaque Psoriasis

Study Overview
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Brief Summary
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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.

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

Conditions
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Psoriasis

Intervention / Treatment
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* Drug: Drug Cocktail
* Drug: Mirikizumab


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Drug Cocktail<br>Drug cocktail administered orally once in Period 1 | Drug: Drug Cocktail<br>* Drug cocktail consists of caffeine, warfarin plus vitamin K, omeprazole, dextromethorphan, and midazolam, administered orally<br>|
| Experimental: Mirikizumab + Drug Cocktail<br>Drug cocktail administered orally once in Period 2 (day 116). Mirikizumab administered subcutaneously (SC) on multiple occasions in Period 2. | Drug: Drug Cocktail<br>* Drug cocktail consists of caffeine, warfarin plus vitamin K, omeprazole, dextromethorphan, and midazolam, administered orally<br>Drug: Mirikizumab<br>* Administered SC<br>* Other names: LY3074828;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Midazolam | PK: Cmax of Midazolam | Period 1, Day 1 Predose through Period 2, Day 117 | 
| PK: Cmax of Warfarin | PK: Cmax of Warfarin | Period 1, Day 1 Predose through Period 2, Day 120 | 
| PK: Cmax of Dextromethorphan | PK: Cmax of Dextromethorphan | Period 1, Day 1 Predose through Period 2, Day 119 | 
| PK: Cmax of Omepraxole | PK: Cmax of Omepraxole | Period 1, Day 1 Predose through Period 2, Day 118 | 
| PK: Cmax of Caffeine | PK: Cmax of Caffeine | Period 1, Day 1 Predose through Period 2, Day 118 | 
| PK: Area Under the Concentration Curve (AUC) Time Zero to Infinity (AUC [0-∞]) of Midazolam | PK: AUC Time Zero to Infinity (AUC[0-∞]) of Midazolam | Period 1, Day 1 Predose through Period 2, Day 117 | 
| PK: AUC Time Zero to Infinity (AUC[0-∞]) of Warfarin | PK: AUC Time Zero to Infinity (AUC[0-∞]) of Warfarin | Period 1, Day 1 Predose through Period 2, Day 120 | 
| PK: AUC Time Zero to Infinity (AUC[0-∞]) of Dextromethorphan | PK: AUC Time Zero to Infinity (AUC[0-∞]) of Dextromethorphan | Period 1, Day 1 Predose through Period 2, Day 119 | 
| PK: AUC Time Zero to Infinity (AUC[0-∞]) of Omepraxole | PK: AUC Time Zero to Infinity (AUC[0-∞]) of Omepraxole | Period 1, Day 1 Predose through Period 2, Day 118 | 
| PK: AUC Time Zero to Infinity (AUC[0-∞]) of Caffeine | PK: AUC Time Zero to Infinity (AUC[0-∞]) of Caffeine | Period 1, Day 1 Predose through Period 2, Day 118 |