A Study of Two Formulations of Ixekizumab in Healthy Participants

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT04259346
• Collaborator: (none)
• Enrollment: 245
• Locations: 4
• Arms: 2
• Actual Duration (Months): 12.5
• Patients Per Site: 61.3
• Patients Per Site Per Month: 4.9

Study Details

Study Description

Brief Summary

The purpose of this study is to compare two different formulations of ixekizumab. One formulation (Reference) is approved by the Food and Drug Administration (FDA) and one formulation (Test) is not approved. This study will compare how much of each formulation gets into the blood stream. Information about any side effects that may occur will also be collected. The study will last up to about four months for each participant.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: Ixekizumab	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 245 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Primary Purpose: Basic Science
• Official Title: Bioequivalence of an Alternate Ixekizumab Formulation Compared to the Commercial Formulation in Healthy Subjects
• Actual Study Start Date: Feb 5, 2020
• Actual Primary Completion Date: Feb 19, 2021
• Actual Study Completion Date: Feb 19, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ixekizumab (Reference) Approved formulation of 80 milligram (mg) ixekizumab administered as a subcutaneous (SC) injection via autoinjector (AI).	Drug: Ixekizumab; Administered SC.; Other Names: LY2439821
Experimental: Ixekizumab (Test) Test formulation of 80 mg ixekizumab administered as a SC injection via AI.	Drug: Ixekizumab; Administered SC.; Other Names: LY2439821

Outcome Measures

Primary Outcome Measures

1. Pharmacokinetics (PK): Maximum Concentration (Cmax) of Ixekizumab [Predose, Day 3, Day 5, Day 8, Day 11, Day 15, Day 22, Day 29, Day 43, Day 57, Day 71 and Day 85 Post Dose]

   PK: Cmax of ixekizumab was evaluated

2. PK: Area Under the Plasma Concentration Versus Time Curve (AUC) From Time Zero to the Last Measured Concentration Value (AUC[0-tlast]) of Ixekizumab [Predose, Day 3, Day 5, Day 8, Day 11, Day 15, Day 22, Day 29, Day 43, Day 57, Day 71 and Day 85 Post Dose]

   Area under the plasma concentration versus time curve from time zero to the last measured concentration value (AUC[0-tlast]). AUC 0-tlast is equal to AUC (0-85) days where the last time point was 85 Days ± 3 Days.

3. PK: Area Under the Plasma Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) of Ixekizumab [Predose, Day 3, Day 5, Day 8, Day 11, Day 15, Day 22, Day 29, Day 43, Day 57, Day 71 and Day 85 Post Dose]

   Area under the plasma concentration versus time curve from zero to infinity (AUC[0-∞]) of a single dose of Ixekizumab.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Are healthy male or female participants, with chronic stable medical problems, that in the investigator's opinion will not place the subject at increased risk by participating in the study

Exclusion Criteria:

• Have a significant history of, or current, cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, or hematologic disorders that in the opinion of the investigator poses an unacceptable risk to the participant if participating in the study

• Are allergic or hypersensitive to the study medicine

• Had a vaccination with a live vaccine within 12 months prior to the first check-in or intend to get a vaccine for tuberculosis within 12 months of completing treatment on this study

• Have any type of hepatitis, human immunodeficiency virus (HIV) infection, or other serious infection

• Show evidence of active or latent tuberculosis (TB)

• Presence of significant neuropsychiatric disorder or a recent history of depression

• Have had any active or recent infection within 4 weeks of Day 1 that, in the opinion of the investigator, would pose an unacceptable risk to the participant

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Covance Clinical Research Inc	Daytona Beach	Florida	United States	32117
2	Miami Research Associates	Miami	Florida	United States	33143
3	Covance Dallas	Dallas	Texas	United States	75247
4	Covance Clinical Research Inc	Madison	Wisconsin	United States	53704

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 - Sep 29, 2020
• Statistical Analysis Plan - Dec 18, 2020

More Information

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT04259346
• Other Study ID Numbers: 17151; I1F-MC-RHCU
• First Posted: Feb 6, 2020
• Last Update Posted: Apr 8, 2022
• Last Verified: Feb 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Ixekizumab

Study Results

Participant Flow

Arm/Group Title	80 Milligram (mg) Ixekizumab (Reference)	80 mg Ixekizumab (Test)
Arm/Group Description	Participants received 80 mg ixekizumab of approved commercial formulation (Reference) administered as a subcutaneous (SC) injection via autoinjector (AI).	Participants received 80 mg ixekizumab alternate formulation (Test) administered as a SC injection via AI.
Period Title: Overall Study
STARTED	126	119
Received at Least One Dose of Study Drug	126	119
COMPLETED	122	115
NOT COMPLETED	4	4

Baseline Characteristics

Arm/Group Title	80 mg Ixekizumab (Reference)	80 mg Ixekizumab (Test)	Total
Arm/Group Description	Participants received 80 mg ixekizumab of approved commercial formulation (Reference) administered as a SC injection via AI.	Participants received 80 mg ixekizumab alternate formulation (Test) administered as a SC injection via AI.	Total of all reporting groups
Overall Participants	126	119	245
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	42.9 (12.8)	46.8 (13.5)	44.8 (13.2)
Sex: Female, Male (Count of Participants)
Female	67 53.2%	60 50.4%	127 51.8%
Male	59 46.8%	59 49.6%	118 48.2%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	58 46%	46 38.7%	104 42.4%
Not Hispanic or Latino	68 54%	73 61.3%	141 57.6%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	1 0.8%	1 0.4%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	32 25.4%	19 16%	51 20.8%
White	93 73.8%	98 82.4%	191 78%
More than one race	1 0.8%	1 0.8%	2 0.8%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
United States	126 100%	119 100%	245 100%

Outcome Measures

1. Primary Outcome

Title	Pharmacokinetics (PK): Maximum Concentration (Cmax) of Ixekizumab
Description	PK: Cmax of ixekizumab was evaluated
Time Frame	Predose, Day 3, Day 5, Day 8, Day 11, Day 15, Day 22, Day 29, Day 43, Day 57, Day 71 and Day 85 Post Dose

Outcome Measure Data

Analysis Population Description

Only participants who had all PK samples collected up to Day 85 or participants who had one missing PK sample after Day 15 but with at least 3 data points and R squared adjusted (Rsq adj) greater than (>) 0.7 to calculate half-life parameter included in the analysis.

Arm/Group Title	80 mg Ixekizumab (Reference)	80 mg Ixekizumab (Test)
Arm/Group Description	Participants received 80 mg ixekizumab of approved commercial formulation (Reference) administered as a SC injection via AI.	Participants received 80 mg ixekizumab alternate formulation (Test) administered as a SC injection via AI.
Measure Participants	112	110
Geometric Mean (Geometric Coefficient of Variation) [micrograms per milliliter (ug/mL)]	9.66 (33)	9.97 (35)

2. Primary Outcome

Title	PK: Area Under the Plasma Concentration Versus Time Curve (AUC) From Time Zero to the Last Measured Concentration Value (AUC[0-tlast]) of Ixekizumab
Description	Area under the plasma concentration versus time curve from time zero to the last measured concentration value (AUC[0-tlast]). AUC 0-tlast is equal to AUC (0-85) days where the last time point was 85 Days ± 3 Days.
Time Frame	Predose, Day 3, Day 5, Day 8, Day 11, Day 15, Day 22, Day 29, Day 43, Day 57, Day 71 and Day 85 Post Dose

Outcome Measure Data

Analysis Population Description

Only participants who had all PK samples collected up to Day 85 or participants who had one missing PK sample after Day 15 but with at least 3 data points and Rsq adj>0.7 to calculate half-life parameter included in the analysis.

Arm/Group Title	80 mg Ixekizumab (Reference)	80 mg Ixekizumab (Test)
Arm/Group Description	Participants received 80 mg ixekizumab of approved commercial formulation (Reference) administered as a SC injection via AI.	Participants received 80 mg ixekizumab alternate formulation (Test) administered as a SC injection via AI.
Measure Participants	112	110
Geometric Mean (Geometric Coefficient of Variation) [microgram*day/milliliter (ug*day/mL)]	207 (31)	219 (28)

3. Primary Outcome

Title	PK: Area Under the Plasma Concentration Versus Time Curve From Zero to Infinity (AUC[0-∞]) of Ixekizumab
Description	Area under the plasma concentration versus time curve from zero to infinity (AUC[0-∞]) of a single dose of Ixekizumab.
Time Frame	Predose, Day 3, Day 5, Day 8, Day 11, Day 15, Day 22, Day 29, Day 43, Day 57, Day 71 and Day 85 Post Dose

Outcome Measure Data

Analysis Population Description

Only participants who had all PK samples collected up to Day 85 or participants who had one missing PK sample after Day 15 but with at least 3 data points and Rsq adj>0.7 to calculate half-life parameter included in the analysis.

Arm/Group Title	80 mg Ixekizumab (Reference)	80 mg Ixekizumab (Test)
Arm/Group Description	Participants received 80 mg ixekizumab of approved commercial formulation (Reference) administered as a SC injection via AI.	Participants received 80 mg ixekizumab alternate formulation (Test) administered as a SC injection via AI.
Measure Participants	112	110
Geometric Mean (Geometric Coefficient of Variation) [ug*day/mL]	213 (33)	227 (30)

Adverse Events

Time Frame	Up to 85 Days
Adverse Event Reporting Description	All randomized participants who received at least one dose of study drug.
Arm/Group Title	80 mg Ixekizumab (Reference)		80 mg Ixekizumab (Test)
Arm/Group Description	Participants received 80 mg ixekizumab of approved commercial formulation (Reference) administered as a SC injection via AI.		Participants received 80 mg ixekizumab alternate formulation (Test) administered as a SC injection via AI.
All Cause Mortality
	80 mg Ixekizumab (Reference)		80 mg Ixekizumab (Test)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/126 (0%)		0/119 (0%)
Serious Adverse Events
	80 mg Ixekizumab (Reference)		80 mg Ixekizumab (Test)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/126 (0%)		0/119 (0%)
Other (Not Including Serious) Adverse Events
	80 mg Ixekizumab (Reference)		80 mg Ixekizumab (Test)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	36/126 (28.6%)		14/119 (11.8%)
General disorders
Injection site reaction	30/126 (23.8%)	30	11/119 (9.2%)	11
Nervous system disorders
Headache	9/126 (7.1%)	11	3/119 (2.5%)	3

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.