A Study of Ixekizumab 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 about how ixekizumab may affect the blood levels of a mixture of commonly used drugs (caffeine, omeprazole, warfarin, dextromethorphan, and midazolam) that are metabolized by cytochrome P450. Each participant will complete two study periods. Participants will take the mixture of commonly used drugs (plus vitamin K) by mouth on 3 occasions (prior to treatment with ixekizumab and after 1 and 12 weeks of treatment with ixekizumab). The study will last about 17 weeks, including follow-up. Screening must be completed prior to study start.

Official Title
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Evaluation of the Effect of Ixekizumab 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: Ixekizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females with chronic moderate or severe plaque psoriasis for at least 6 months who are candidates for systemic therapy or phototherapy Men and women of childbearing potential must agree to use a reliable method of birth control and men may not donate sperm for the duration of the study. Women must test negative for pregnancy at screening and agree not to become pregnant during the study and until the first normal period following the end of the study Have a body mass index (BMI) of 18.5 to 40.0 kilograms per square meter (kg/m²), inclusive, at screening Have greater than or equal to (≥) 10 percent body surface area (BSA) involvement at screening and first admission to the clinical research unit (CRU) Have both a Static Physicians Global Assessment (sPGA) score of ≥3 and Psoriasis Area Severity Index (PASI) score ≥12 at screening and first admission to the CRU Exclusion Criteria: Forms of psoriasis other than chronic plaque-type Pregnant or nursing (lactating women) 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 research unit or during the study Have a history of lymphoproliferative disease, or signs or symptoms of lymphoproliferative disease, or have active or history of malignant disease, or have uncontrolled cerebrocardiovascular or neuropsychiatric disease Require treatment with the cocktail drugs or with inhibitors of cytochrome P450 (CYP) 3A, CYP2C9, CYP2D6, CYP2C19, CYP1A2, or with inducers of CYP3A or CYP1A2, or with rifampin (inducer of multiple CYPs) or with substrates of CYP3A, CYP2C9, CYP2D6, CYP2C19, or CYP1A2 with narrow therapeutic indices within 14 days prior to the first administration of the drug cocktail through the end of Week 12 assessments Have any known allergy or hypersensitivity to any component of the study cocktail or ixekizumab Have participated in any other study with ixekizumab, secukinumab or brodalumab, or have been prescribed ixekizumab or secukinumab

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: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Drug Cocktail<br>Drug cocktail (caffeine, warfarin [plus vitamin K], omeprazole, dextromethorphan, and midazolam) administered orally once in Period 1 (day 1). | Drug: Drug Cocktail<br>* Administered orally<br>* Other names: Caffeine + Warfarin (plus vitamin K) + Omeprazole + Dextromethorphan + Midazolam;|
| Experimental: Drug Cocktail + Ixekizumab<br>Drug cocktail (caffeine, warfarin [plus vitamin K], omeprazole, dextromethorphan, and midazolam) administered orally twice in Period 2 (day 8 and day 85). Ixekizumab administered subcutaneously (SC) on multiple occasions in Period 2. | Drug: Drug Cocktail<br>* Administered orally<br>* Other names: Caffeine + Warfarin (plus vitamin K) + Omeprazole + Dextromethorphan + Midazolam;Drug: Ixekizumab<br>* Administered SC<br>* Other names: LY2439821;|

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 Cytochrome P450 (CYP450) Substrate-Midazolam | Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Cytochrome P450 (CYP450) Substrate (Midazolam) | Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose | 
| Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) of CYP450 Substrate-Midazolam | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve from Zero to Infinity (AUC[0-∞]) of CYP450 Substrate (Midazolam) | Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose | 
| Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of CYP450 Substrate-Warfarin | Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of CYP450 Substrate (Warfarin) | Predose, 1, 2, 4, 6, 8, 10, 24, 48, 72, and 96 hours postdose | 
| Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) of CYP450 Substrate-Warfarin | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve from Zero to Infinity (AUC[0-∞]) of CYP450 Substrate (Warfarin) | Predose, 1, 2, 4, 6, 8, 10, 24, 48, 72, and 96 hours postdose | 
| Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of CYP450 Substrate-Dextromethorphan | Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of CYP450 Substrate (Dextromethorphan) | Predose, 1, 2, 4, 6, 8, 10, 24, 48, and 72 hours postdose | 
| Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) of CYP450 Substrate-Dextromethorphan | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve from Zero to Infinity (AUC[0-∞]) of CYP450 Substrate (Dextromethorphan) | Predose, 1, 2, 4, 6, 8, 10, 24, 48, and 72 hours postdose | 
| Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of CYP450 Substrate-Omeprazole and Its Metabolite 5-Hydroxyomeprazole | Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of CYP450 Substrate (Omeprazole and its metabolite 5-Hydroxyomeprazole) | Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, and 48 hours postdose | 
| Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) of CYP450 Substrate-Omeprazole and Its Metabolite 5-Hydroxyomeprazole | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve from Zero to Infinity (AUC[0-∞]) of CYP450 Substrate (Omeprazole and its metabolite 5-Hydroxyomeprazole) | Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, and 48 hours postdose | 
| Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of CYP450 Substrate-Caffeine | Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of CYP450 Substrate (Caffeine) | Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, and 48 hours postdose | 
| Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to 48 Hours (AUC[0-48h]) of CYP450 Substrate-Caffeine | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve from Zero to 48 hours (AUC[0-48h]) of CYP450 Substrate (Caffeine) | Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, and 48 hours postdose |