A Study of Ixekizumab in Participants With Plaque Psoriasis

Phase 1

Completed

• Conditions: Psoriasis
• Interventions: Drug: Drug Cocktail; Drug: Ixekizumab

• Registration Number: NCT02993471
• Lead Sponsor: Eli Lilly and Company

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2016-12-13
• Study First Submitted QC: 2016-12-13
• Study First Posted: 2016-12-15
• Study Start: 2016-12-22
• Primary Completion: 2017-11-21
• Study Completion: 2017-11-21
• Status Verified: 2017-12
• Results First Submitted: 2018-11-20
• Results First Submitted QC: 2018-11-20
• Last Update Submitted: 2018-11-20
• Results First Posted: 2019-03-12
• Last Update Posted: 2019-03-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 28

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Drug Cocktail + Ixekizumab	Drug Cocktail	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 Cocktail	Drug Cocktail	Drug cocktail (caffeine, warfarin \[plus vitamin K\], omeprazole, dextromethorphan, and midazolam) administered orally once in Period 1 (day 1).
Drug Cocktail + Ixekizumab	Ixekizumab	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.

Primary Outcome Measures

Name	Time	Method
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): Area Under the Concentration Versus Time Curve from Zero to Infinity (AUC\[0-∞\]) of CYP450 Substrate (Dextromethorphan)
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): Maximum Observed Drug Concentration (Cmax) of CYP450 Substrate (Omeprazole and its metabolite 5-Hydroxyomeprazole)
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): Maximum Observed Drug Concentration (Cmax) of CYP450 Substrate (Warfarin)
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): 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-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 48 Hours (AUC[0-48h]) 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): 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): Maximum Observed Drug Concentration (Cmax) of Cytochrome P450 (CYP450) Substrate (Midazolam)
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): Area Under the Concentration Versus Time Curve from Zero to Infinity (AUC\[0-∞\]) of CYP450 Substrate (Warfarin)
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): Maximum Observed Drug Concentration (Cmax) of CYP450 Substrate (Dextromethorphan)
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): Maximum Observed Drug Concentration (Cmax) of CYP450 Substrate (Caffeine)

Trial Locations

Locations (3)

Anaheim Clinical Trials, LLC; 🇺🇸 Anaheim, California, United States

Avail Clinical Research LLC; 🇺🇸 DeLand, Florida, United States

High Point Clinical Trials Center; 🇺🇸 High Point, North Carolina, United States