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Trial record 25 of 158 for:    warfarin AND Vitamin K

A Study of Ixekizumab in Participants With Plaque Psoriasis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02993471
Recruitment Status : Completed
First Posted : December 15, 2016
Results First Posted : March 12, 2019
Last Update Posted : March 12, 2019
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Basic Science
Condition Psoriasis
Interventions Drug: Drug Cocktail
Drug: Ixekizumab
Enrollment 28
Recruitment Details  
Pre-assignment Details Multicenter, open-label, 2-period, fixed-sequence study.
Arm/Group Title Drug Cocktail /Drug Cocktail + Ixekizumab
Hide 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 2 (Drug Cocktail + Ixekizumab)
Started 28
Received at Least 1 Dose of Study Drug 27
Completed 26
Not Completed 2
Reason Not Completed
Protocol Violation             1
Withdrawal by Subject             1
Arm/Group Title Overall Study
Hide Arm/Group Description Participants received drug cocktail and drug cocktail + Ixekizumab.
Overall Number of Baseline Participants 28
Hide Baseline Analysis Population Description
All enrolled participants who received at least 1 dose of study drug.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 28 participants
41.8  (14.62)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 28 participants
Female 7
Male 21
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 28 participants
Hispanic or Latino 14
Not Hispanic or Latino 14
Unknown or Not Reported 0
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 28 participants
American Indian or Alaska Native 0
Asian 2
Native Hawaiian or Other Pacific Islander 0
Black or African American 1
White 25
More than one race 0
Unknown or Not Reported 0
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 28 participants
28
1.Primary Outcome
Title Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Cytochrome P450 (CYP450) Substrate-Midazolam
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 27 26 25
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: 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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 27 26 25
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: 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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 27 26 25
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: 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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 27 26 25
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*h/mL
17600
(29%)
17700
(31%)
16200
(29%)
5.Primary Outcome
Title Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of CYP450 Substrate-Dextromethorphan
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 27 25 24
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: 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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 25 24 23
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: 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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 27 26 25
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 22 23 21
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*h/mL
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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 18 21 13
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: 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
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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.
Overall Number of Participants Analyzed 13 19 11
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng*h/mL
25000
(48%)
22400
(57%)
22400
(36%)
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
Hide 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 (%) Affected / at Risk (%)
Total   0/28 (0.00%)      0/27 (0.00%)    
Hide Serious Adverse Events
Drug Cocktail Drug Cocktail + Ixekizumab
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/28 (0.00%)      0/27 (0.00%)    
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Drug Cocktail Drug Cocktail + Ixekizumab
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/28 (3.57%)      7/27 (25.93%)    
Gastrointestinal disorders     
Diarrhoea  1  0/28 (0.00%)  0 1/27 (3.70%)  1
Nausea  1  0/28 (0.00%)  0 1/27 (3.70%)  1
General disorders     
Chest discomfort  1  0/28 (0.00%)  0 1/27 (3.70%)  1
Peripheral swelling  1  0/28 (0.00%)  0 1/27 (3.70%)  1
Infections and infestations     
Cellulitis of male external genital organ  1  0/28 (0.00%)  0 1/27 (3.70%)  1
Pharyngitis  1  0/28 (0.00%)  0 1/27 (3.70%)  1
Upper respiratory tract infection  1  0/28 (0.00%)  0 1/27 (3.70%)  1
Musculoskeletal and connective tissue disorders     
Arthralgia  1  0/28 (0.00%)  0 1/27 (3.70%)  1
Back pain  1  0/28 (0.00%)  0 1/27 (3.70%)  1
Nervous system disorders     
Dizziness  1  0/28 (0.00%)  0 1/27 (3.70%)  1
Headache  1  1/28 (3.57%)  1 1/27 (3.70%)  1
Respiratory, thoracic and mediastinal disorders     
Cough  1  0/28 (0.00%)  0 1/27 (3.70%)  1
Skin and subcutaneous tissue disorders     
Alopecia  1  0/28 (0.00%)  0 1/27 (3.70%)  1
Psoriasis  1  0/28 (0.00%)  0 1/27 (3.70%)  1
1
Term from vocabulary, MedDRA 19.1
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Chief Medical Officer
Organization: Eli Lilly and Company
Phone: 800-545-5979
EMail: ClinicalTrials.gov@lilly.com
Layout table for additonal information
Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT02993471    
Other Study ID Numbers: 16126
I1F-MC-RHBU ( Other Identifier: Eli Lilly and Company )
First Submitted: December 13, 2016
First Posted: December 15, 2016
Results First Submitted: November 20, 2018
Results First Posted: March 12, 2019
Last Update Posted: March 12, 2019