A Study of Ixekizumab in Participants With Plaque Psoriasis

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

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.

Study Overview

• Status: Completed
• Conditions: Psoriasis
• Intervention / Treatment: Drug: Drug Cocktail; Drug: Ixekizumab

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Anaheim, California, United States, 92801
      • Anaheim Clinical Trials, LLC
  • Florida
    • DeLand, Florida, United States, 32720
      • Avail Clinical Research LLC
  • North Carolina
    • High Point, North Carolina, United States, 27265
      • High Point Clinical Trials Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Drug Cocktail; Drug cocktail (caffeine, warfarin [plus vitamin K], omeprazole, dextromethorphan, and midazolam) administered orally once in Period 1 (day 1).	Drug: Drug Cocktail; Administered orally; Other Names: Caffeine + Warfarin (plus vitamin K) + Omeprazole + Dextromethorphan + Midazolam
Experimental: Drug Cocktail + 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.	Drug: Drug Cocktail; Administered orally; Other Names: Caffeine + Warfarin (plus vitamin K) + Omeprazole + Dextromethorphan + Midazolam; Drug: Ixekizumab; Administered SC; Other Names: LY2439821

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Publications and helpful links

Helpful Links

• Click here for more information about this study: A Study of Ixekizumab in Participants with Plaque Psoriasis

Study record dates

Study Major Dates

• Study Start (Actual): December 22, 2016
• Primary Completion (Actual): November 21, 2017
• Study Completion (Actual): November 21, 2017

Study Registration Dates

• First Submitted: December 13, 2016
• First Submitted That Met QC Criteria: December 13, 2016
• First Posted (Estimate): December 15, 2016

Study Record Updates

• Last Update Posted (Actual): March 12, 2019
• Last Update Submitted That Met QC Criteria: November 20, 2018
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Skin Diseases, Papulosquamous; Psoriasis; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Enzyme Inhibitors; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Fibrin Modulating Agents; Purinergic Antagonists; Purinergic Agents; Gastrointestinal Agents; Dermatologic Agents; Micronutrients; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Respiratory System Agents; Vitamins; Anticoagulants; Antifibrinolytic Agents; Hemostatics; Coagulants; Anti-Ulcer Agents; Proton Pump Inhibitors; Phosphodiesterase Inhibitors; Purinergic P1 Receptor Antagonists; Central Nervous System Stimulants; Antitussive Agents; Midazolam; Vitamin K; Dextromethorphan; Warfarin; Caffeine; Omeprazole; Ixekizumab
• Other Study ID Numbers: 16126; I1F-MC-RHBU (Other Identifier: Eli Lilly and Company)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No