Clinical trial NCT02993471: A Study of Ixekizumab in Participants With Plaque Psoriasis
Official title: Evaluation of the Effect of Ixekizumab on the Pharmacokinetics of Cytochrome P450 Substrates in Patients With Moderate-to-Severe Plaque Psoriasis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Psoriasis
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2016-12-15
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: 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

Primary outcomes:
measure: Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Cytochrome P450 (CYP450) Substrate-Midazolam
timeFrame: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose
measure: Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) of CYP450 Substrate-Midazolam
timeFrame: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose
measure: Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of CYP450 Substrate-Warfarin
timeFrame: Predose, 1, 2, 4, 6, 8, 10, 24, 48, 72, and 96 hours postdose
measure: Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) of CYP450 Substrate-Warfarin
timeFrame: Predose, 1, 2, 4, 6, 8, 10, 24, 48, 72, and 96 hours postdose
measure: Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of CYP450 Substrate-Dextromethorphan
timeFrame: Predose, 1, 2, 4, 6, 8, 10, 24, 48, and 72 hours postdose
measure: Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) of CYP450 Substrate-Dextromethorphan
timeFrame: Predose, 1, 2, 4, 6, 8, 10, 24, 48, and 72 hours postdose
measure: Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of CYP450 Substrate-Omeprazole and Its Metabolite 5-Hydroxyomeprazole
timeFrame: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, and 48 hours postdose
measure: Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) of CYP450 Substrate-Omeprazole and Its Metabolite 5-Hydroxyomeprazole
timeFrame: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, and 48 hours postdose
measure: Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of CYP450 Substrate-Caffeine
timeFrame: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, and 48 hours postdose
measure: Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to 48 Hours (AUC[0-48h]) of CYP450 Substrate-Caffeine
timeFrame: Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, and 48 hours postdose
Secondary outcomes:
Other outcomes:
Locations:
city: Anaheim
country: United States
facility: Anaheim Clinical Trials, LLC
state: California
city: DeLand
country: United States
facility: Avail Clinical Research LLC
state: Florida
city: High Point
country: United States
facility: High Point Clinical Trials Center
state: North Carolina
Study officials:
affiliation: Eli Lilly and Company
name: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
role: STUDY_DIRECTOR
References: