A Study of Ixekizumab in Participants With Plaque Psoriasis

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02993471
• Collaborator: (none)
• Enrollment: 28
• Locations: 3
• Arms: 2
• Actual Duration (Months): 11
• Patients Per Site: 9.3
• Patients Per Site Per Month: 0.9

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Psoriasis	Drug: Drug Cocktail; Drug: Ixekizumab	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 28 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: Evaluation of the Effect of Ixekizumab on the Pharmacokinetics of Cytochrome P450 Substrates in Patients With Moderate-to-Severe Plaque Psoriasis
• Actual Study Start Date: Dec 22, 2016
• Actual Primary Completion Date: Nov 21, 2017
• Actual Study Completion Date: Nov 21, 2017

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 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)

2. 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)

3. 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)

4. 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)

5. 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)

6. 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)

7. 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)

8. 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)

9. 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)

10. 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)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Anaheim Clinical Trials, LLC	Anaheim	California	United States	92801
2	Avail Clinical Research LLC	DeLand	Florida	United States	32720
3	High Point Clinical Trials Center	High Point	North Carolina	United States	27265

Sponsors and Collaborators

• Eli Lilly and Company

Investigators

• Study Director: 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), Eli Lilly and Company

Study Documents (Full-Text)

• Study Protocol - Dec 8, 2016
• Statistical Analysis Plan - May 31, 2017

More Information

Additional Information:

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

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT02993471
• Other Study ID Numbers: 16126; I1F-MC-RHBU
• First Posted: Dec 15, 2016
• Last Update Posted: Mar 12, 2019
• Last Verified: Dec 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Psoriasis; Vitamin K; Midazolam; Dextromethorphan; Caffeine; Ixekizumab; Omeprazole; Warfarin

Study Results

Participant Flow

Pre-assignment Detail	Multicenter, open-label, 2-period, fixed-sequence study.

Arm/Group Title	Drug Cocktail /Drug Cocktail + Ixekizumab
Arm/Group Description	Period 1: Participants received drug cocktail (100 mg Caffeine, 10 mg Warfarin [plus vitamin K], 20 mg Omeprazole, 30 mg Dextromethorphan, and 1 mg Midazolam) administered orally on Day 1. Participants resided at the Clinical Research Unit (CRU) until Day 2, and were discharged following collection of 24-hour pharmacokinetics (PK) samples for the determination of plasma concentrations of the cocktail drugs and metabolites. Period 2: Participants received a 160 mg dose of Ixekizumab during an outpatient visit on Day 1 (3 to 7 days after Day 5 of Period 1) and were admitted to the CRU on Day 7 (±2 days) to receive the drug cocktail on the morning of Day 8 (Week 1). Participants received single 80 mg doses of Ixekizumab at outpatient visits on Day 15 (Week 2), Day 29 (Week 4), Day 43 (Week 6), Day 57 (Week 8), and Day 71 (Week 10). Participants were admitted to the CRU on Day 84 (±2 days) and received 80 mg Ixekizumab and the drug cocktail on the following morning (Day 85; Week 12).
Period Title: Period 1 (Drug Cocktail)
STARTED	28
Received at Least 1 Dose of Study Drug	28
COMPLETED	28
NOT COMPLETED	0
Period Title: Period 1 (Drug Cocktail)
STARTED	28
Received at Least 1 Dose of Study Drug	27
COMPLETED	26
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	Overall Study
Arm/Group Description	Participants received drug cocktail and drug cocktail + Ixekizumab.
Overall Participants	28
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	41.8 (14.62)
Sex: Female, Male (Count of Participants)
Female	7 25%
Male	21 75%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	14 50%
Not Hispanic or Latino	14 50%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	2 7.1%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	1 3.6%
White	25 89.3%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (Count of Participants)
United States	28 100%

Outcome Measures

1. Primary Outcome

Title	Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Cytochrome P450 (CYP450) Substrate-Midazolam
Description	Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Cytochrome P450 (CYP450) Substrate (Midazolam)
Time Frame	Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose

Outcome Measure Data

Analysis Population Description

All enrolled participants who received at least 1 dose of study drug with evaluable PK data.

Arm/Group Title	1 mg Midazolam	160 mg Ixekizumab + 1 mg Midazolam	80 mg Ixekizumab Q2W (Once Every Two Weeks) + 1 mg Midazolam
Arm/Group Description	Participants received 1 mg of Midazolam on Day 1 of Period 1.	Participants received 160 mg dose of Ixekizumab on Day 1 and 1 mg of Midazolam on Day 8 of Period 2.	Participants received 80 mg of Ixekizumab on Day 15, Day 29, Day 43, Day 57, and Day 71. Participants were admitted to the CRU on Day 84 (±2 days) and received 80 mg of Ixekizumab and 1 mg of Midazolam on the following morning (Day 85; Week 12) during Period 2.
Measure Participants	27	26	25
Geometric Mean (Geometric Coefficient of Variation) [nanogram per milliliter (ng/mL)]	4.56 (24)	4.92 (24)	4.83 (26)

2. Primary Outcome

Title	Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) of CYP450 Substrate-Midazolam
Description	Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve from Zero to Infinity (AUC[0-∞]) of CYP450 Substrate (Midazolam)
Time Frame	Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose

Outcome Measure Data

Analysis Population Description

All enrolled participants who received at least 1 dose of study drug with evaluable PK data.

Arm/Group Title	1 mg Midazolam	160 mg Ixekizumab + 1 mg Midazolam	80 mg Ixekizumab Q2W + 1 mg Midazolam
Arm/Group Description	Participants received 1 mg of Midazolam on Day 1 of Period 1.	Participants received 160 mg dose of Ixekizumab on Day 1 and 1 mg of Midazolam on Day 8 of Period 2.	Participants received 80 mg of Ixekizumab on Day 15, Day 29, Day 43, Day 57, and Day 71. Participants were admitted to the CRU on Day 84 (±2 days) and received 80 mg of Ixekizumab and 1 mg of Midazolam on the following morning (Day 85; Week 12) during Period 2.
Measure Participants	27	26	25
Geometric Mean (Geometric Coefficient of Variation) [nanogram*hour per milliliter (ng*h/mL)]	16.6 (28)	15.9 (27)	15.4 (34)

3. Primary Outcome

Title	Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of CYP450 Substrate-Warfarin
Description	Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of CYP450 Substrate (Warfarin)
Time Frame	Predose, 1, 2, 4, 6, 8, 10, 24, 48, 72, and 96 hours postdose

Outcome Measure Data

Analysis Population Description

All enrolled participants who received at least 1 dose of study drug with evaluable PK data.

Arm/Group Title	10 mg Warfarin	160 mg Ixekizumab + 10 mg Warfarin	80 mg Ixekizumab Q2W + 10 mg Warfarin
Arm/Group Description	Participants received 10 mg of Warfarin on Day 1 of Period 1.	Participants received 160 mg dose of Ixekizumab on Day 1 and 10 mg of Warfarin on Day 8 of Period 2.	Participants received 80 mg of Ixekizumab on Day 15, Day 29, Day 43, Day 57, and Day 71. Participants were admitted to the CRU on Day 84 (±2 days) and received 80 mg of Ixekizumab and 10 mg of Warfarin on the following morning (Day 85; Week 12) during Period 2.
Measure Participants	27	26	25
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	510 (26)	525 (22)	510 (23)

4. Primary Outcome

Title	Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) of CYP450 Substrate-Warfarin
Description	Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve from Zero to Infinity (AUC[0-∞]) of CYP450 Substrate (Warfarin)
Time Frame	Predose, 1, 2, 4, 6, 8, 10, 24, 48, 72, and 96 hours postdose

Outcome Measure Data

Analysis Population Description

All enrolled participants who received at least 1 dose of study drug with evaluable PK data.

Arm/Group Title	10 mg Warfarin	160 mg Ixekizumab + 10 mg Warfarin	80 mg Ixekizumab Q2W + 10 mg Warfarin
Arm/Group Description	Participants received 10 mg of Warfarin on Day 1 of Period 1.	Participants received 160 mg dose of Ixekizumab on Day 1 and 10 mg of Warfarin on Day 8 of Period 2.	Participants received 80 mg of Ixekizumab on Day 15, Day 29, Day 43, Day 57, and Day 71. Participants were admitted to the CRU on Day 84 (±2 days) and received 80 mg of Ixekizumab and 10 mg of Warfarin on the following morning (Day 85; Week 12) during Period 2.
Measure Participants	27	26	25
Geometric Mean (Geometric Coefficient of Variation) [ng*h/mL]	17600 (29)	17700 (31)	16200 (29)

5. Primary Outcome

Title	Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of CYP450 Substrate-Dextromethorphan
Description	Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of CYP450 Substrate (Dextromethorphan)
Time Frame	Predose, 1, 2, 4, 6, 8, 10, 24, 48, and 72 hours postdose

Outcome Measure Data

Analysis Population Description

All enrolled participants who received at least 1 dose of study drug with evaluable PK data.

Arm/Group Title	30 mg Dextromethorphan	160 mg Ixekizumab + 30 mg Dextromethorphan	80 mg Ixekizumab Q2W + 30 mg Dextromethorphan
Arm/Group Description	Participants received 30 mg of Dextromethorphan on Day 1 of Period 1.	Participants received 160 mg dose of Ixekizumab on Day 1 and 30 mg of Dextromethorphan on Day 8 of Period 2.	Participants received 80 mg of Ixekizumab on Day 15, Day 29, Day 43, Day 57, and Day 71. Participants were admitted to the CRU on Day 84 (±2 days) and received 80 mg of Ixekizumab and 30 mg of Dextromethorphan on the following morning (Day 85; Week 12) during Period 2.
Measure Participants	27	25	24
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	0.691 (291)	0.878 (202)	0.658 (285)

6. Primary Outcome

Title	Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) of CYP450 Substrate-Dextromethorphan
Description	Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve from Zero to Infinity (AUC[0-∞]) of CYP450 Substrate (Dextromethorphan)
Time Frame	Predose, 1, 2, 4, 6, 8, 10, 24, 48, and 72 hours postdose

Outcome Measure Data

Analysis Population Description

All enrolled participants who received at least 1 dose of study drug with evaluable PK data.

Arm/Group Title	30 mg Dextromethorphan	160 mg Ixekizumab + 30 mg Dextromethorphan	80 mg Ixekizumab Q2W + 30 mg Dextromethorphan
Arm/Group Description	Participants received 30 mg of Dextromethorphan on Day 1 of Period 1.	Participants received 160 mg dose of Ixekizumab on Day 1 and 30 mg of Dextromethorphan on Day 8 of Period 2.	Participants received 80 mg of Ixekizumab on Day 15, Day 29, Day 43, Day 57, and Day 71. Participants were admitted to the CRU on Day 84 (±2 days) and received 80 mg of Ixekizumab and 30 mg of Dextromethorphan on the following morning (Day 85; Week 12) during Period 2.
Measure Participants	25	24	23
Geometric Mean (Geometric Coefficient of Variation) [ng*h/mL]	11.7 (254)	12.6 (225)	8.53 (273)

7. Primary Outcome

Title	Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of CYP450 Substrate-Omeprazole and Its Metabolite 5-Hydroxyomeprazole
Description	Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of CYP450 Substrate (Omeprazole and its metabolite 5-Hydroxyomeprazole)
Time Frame	Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, and 48 hours postdose

Outcome Measure Data

Analysis Population Description

All enrolled participants who received at least 1 dose of study drug with evaluable PK data.

Arm/Group Title	20 mg Omeprazole	160 mg Ixekizumab + 20 mg Omeprazole	80 mg Ixekizumab Q2W + 20 mg Omeprazole
Arm/Group Description	Participants received 20 mg of Omeprazole on Day 1 of Period 1.	Participants received 160 mg dose of Ixekizumab on Day 1 and 20 mg of Omeprazole on Day 8 of Period 2.	Participants received 80 mg of Ixekizumab on Day 15, Day 29, Day 43, Day 57, and Day 71. Participants were admitted to the CRU on Day 84 (±2 days) and received 80 mg of Ixekizumab and 20 mg of Omeprazole on the following morning (Day 85; Week 12) during Period 2.
Measure Participants	27	26	25
Omeprazole	333 (83)	340 (74)	368 (62)
5-Hydroxyomeprazole	148 (55)	143 (57)	137 (46)

8. Primary Outcome

Title	Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) of CYP450 Substrate-Omeprazole and Its Metabolite 5-Hydroxyomeprazole
Description	Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve from Zero to Infinity (AUC[0-∞]) of CYP450 Substrate (Omeprazole and its metabolite 5-Hydroxyomeprazole)
Time Frame	Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, and 48 hours postdose

Outcome Measure Data

Analysis Population Description

All enrolled participants who received at least 1 dose of study drug with evaluable PK data.

Arm/Group Title	20 mg Omeprazole	160 mg Ixekizumab + 20 mg Omeprazole	80 mg Ixekizumab Q2W + 20 mg Omeprazole
Arm/Group Description	Participants received 20 mg of Omeprazole on Day 1 of Period 1.	Participants received 160 mg dose of Ixekizumab on Day 1 and 20 mg of Omeprazole on Day 8 of Period 2.	Participants received 80 mg of Ixekizumab on Day 15, Day 29, Day 43, Day 57, and Day 71. Participants were admitted to the CRU on Day 84 (±2 days) and received 80 mg of Ixekizumab and 20 mg of Omeprazole on the following morning (Day 85; Week 12) during Period 2.
Measure Participants	22	23	21
Omeprazole	1060 (104)	829 (129)	913 (107)
5-Hydroxyomeprazole	519 (28)	475 (25)	455 (24)

9. Primary Outcome

Title	Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of CYP450 Substrate-Caffeine
Description	Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of CYP450 Substrate (Caffeine)
Time Frame	Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, and 48 hours postdose

Outcome Measure Data

Analysis Population Description

All enrolled participants who received at least 1 dose of study drug with evaluable PK data.

Arm/Group Title	100 mg Caffeine	160 mg Ixekizumab + 100 mg Caffeine	80 mg Ixekizumab Q2W + 100 mg Caffeine
Arm/Group Description	Participants received 100 mg of Caffeine on Day 1 of Period 1.	Participants received 160 mg dose of ixekizumab on Day 1 and 100 mg of Caffeine on Day 8 of Period 2.	Participants received 80 mg of ixekizumab on Day 15, Day 29, Day 43, Day 57, and Day 71. Participants were admitted to the CRU on Day 84 (±2 days) and received 80 mg of ixekizumab and 100 mg of Caffeine on the following morning (Day 85; Week 12) during Period 2.
Measure Participants	18	21	13
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	2230 (19)	2220 (22)	2240 (22)

10. Primary Outcome

Title	Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Zero to 48 Hours (AUC[0-48h]) of CYP450 Substrate-Caffeine
Description	Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve from Zero to 48 hours (AUC[0-48h]) of CYP450 Substrate (Caffeine)
Time Frame	Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, and 48 hours postdose

Outcome Measure Data

Analysis Population Description

All enrolled participants who received at least 1 dose of study drug with evaluable PK data.

Arm/Group Title	100 mg Caffeine	160 mg Ixekizumab + 100 mg Caffeine	80 mg Ixekizumab Q2W + 100 mg Caffeine
Arm/Group Description	Participants received 100 mg of Caffeine on Day 1 of Period 1.	Participants received 160 mg dose of Ixekizumab on Day 1 and 100 mg of Caffeine on Day 8 of Period 2.	Participants received 80 mg of Ixekizumab on Day 15, Day 29, Day 43, Day 57, and Day 71. Participants were admitted to the CRU on Day 84 (±2 days) and received 80 mg of Ixekizumab and 100 mg of Caffeine on the following morning (Day 85; Week 12) during Period 2.
Measure Participants	13	19	11
Geometric Mean (Geometric Coefficient of Variation) [ng*h/mL]	25000 (48)	22400 (57)	22400 (36)

Adverse Events

Time Frame	Up To 89 days
Adverse Event Reporting Description	All enrolled participants who received at least 1 dose of study drug.
Arm/Group Title	Drug Cocktail		Drug Cocktail + Ixekizumab
Arm/Group Description	Participants received drug cocktail (100 mg Caffeine, 10 mg Warfarin [plus vitamin K], 20 mg Omeprazole, 30 mg Dextromethorphan, and 1 mg Midazolam) administered orally on Day 1 of period 1.		Participants received a 160 mg dose of Ixekizumab during an outpatient visit on Day 1 (3 to 7 days after Day 5 of Period 1) and were admitted to the CRU on Day 7 (±2 days) to receive the drug cocktail on the morning of Day 8 (Week 1). Participants received single 80 mg doses of Ixekizumab at outpatient visits on Day 15 (Week 2), Day 29 (Week 4), Day 43 (Week 6), Day 57 (Week 8), and Day 71 (Week 10). Participants were admitted to the CRU on Day 84 (±2 days) and received 80 mg Ixekizumab and the drug cocktail on the following morning (Day 85; Week 12).
All Cause Mortality
	Drug Cocktail		Drug Cocktail + Ixekizumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/28 (0%)		0/27 (0%)
Serious Adverse Events
	Drug Cocktail		Drug Cocktail + Ixekizumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/28 (0%)		0/27 (0%)
Other (Not Including Serious) Adverse Events
	Drug Cocktail		Drug Cocktail + Ixekizumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/28 (3.6%)		7/27 (25.9%)
Gastrointestinal disorders
Diarrhoea	0/28 (0%)	0	1/27 (3.7%)	1
Nausea	0/28 (0%)	0	1/27 (3.7%)	1
General disorders
Chest discomfort	0/28 (0%)	0	1/27 (3.7%)	1
Peripheral swelling	0/28 (0%)	0	1/27 (3.7%)	1
Infections and infestations
Cellulitis of male external genital organ	0/28 (0%)	0	1/27 (3.7%)	1
Pharyngitis	0/28 (0%)	0	1/27 (3.7%)	1
Upper respiratory tract infection	0/28 (0%)	0	1/27 (3.7%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	0/28 (0%)	0	1/27 (3.7%)	1
Back pain	0/28 (0%)	0	1/27 (3.7%)	1
Nervous system disorders
Dizziness	0/28 (0%)	0	1/27 (3.7%)	1
Headache	1/28 (3.6%)	1	1/27 (3.7%)	1
Respiratory, thoracic and mediastinal disorders
Cough	0/28 (0%)	0	1/27 (3.7%)	1
Skin and subcutaneous tissue disorders
Alopecia	0/28 (0%)	0	1/27 (3.7%)	1
Psoriasis	0/28 (0%)	0	1/27 (3.7%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.