A First Human Study of a Ferroportin Antibody

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01330953
• Collaborator: (none)
• Enrollment: 32
• Location: 1
• Arms: 5
• Duration (Months): 6
• Patients Per Site Per Month: 5.3

Study Details

Study Description

Brief Summary

The purposes of this study are to evaluate the following in healthy participants: 1) LY2928057 safety, including any side effects possibly associated with LY2928057; 2) how the body processes LY2928057; 3) effect of LY2928057 on blood iron levels; and 4) immune system reactions to LY2928057.

Condition or Disease	Intervention/Treatment	Phase
Healthy Volunteers	Drug: Placebo; Drug: LY2928057	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 32 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Primary Purpose: Basic Science
• Official Title: A Single-Dose, Dose-Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of LY2928057 in Healthy Subjects
• Study Start Date: Mar 1, 2011
• Actual Primary Completion Date: Sep 1, 2011
• Actual Study Completion Date: Sep 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Single intravenous placebo dose.	Drug: Placebo; Single intravenous placebo dose.
Experimental: 30 mg LY2928057 (Cohort 1) Day 1: single 30-milligram (mg) LY2928057 intravenous dose; Days 2 and 3: observation period; Days 4 and 5: single 30-mg LY2928057 intravenous dose followed by 24-hour observation period; Days 6 and 7: single 30-mg LY2928057 intravenous dose; Days 8-85: participant follow-up for minimum of 12 weeks to assess the safety, immunogenicity, and pharmacokinetic profile of 30 mg LY2928057.	Drug: LY2928057; Single intravenous dose.; Other Names: Ferroportin antibody
Experimental: 100 mg LY2928057 (Cohort 2) Day 1: single 100-mg LY2928057 intravenous dose; Days 2 and 3: observation period; Days 4 and 5: single 100-mg LY2928057 intravenous dose followed by 24-hour observation period; Days 6 and 7: single 100-mg LY2928057 intravenous dose; Days 8-85: participant follow-up for minimum of 12 weeks to assess the safety, immunogenicity, and pharmacokinetic profile of 100 mg LY2928057.	Drug: LY2928057; Single intravenous dose.; Other Names: Ferroportin antibody
Experimental: 300 mg LY2928057 (Cohort 3) Day 1: single 300-mg LY2928057 intravenous dose; Days 2 and 3: observation period; Days 4 and 5: single 300-mg LY2928057 intravenous dose followed by 24-hour observation period; Days 6 and 7: single 300-mg LY2928057 intravenous dose; Days 8-85: participant follow-up for minimum of 12 weeks to assess the safety, immunogenicity, and pharmacokinetic profile of 300 mg LY2928057.	Drug: LY2928057; Single intravenous dose.; Other Names: Ferroportin antibody
Experimental: 1000 mg LY2928057 (Cohort 4) Day 1: single 1000-mg LY2928057 intravenous dose; Days 2 and 3: observation period; Days 4 and 5: single 1000-mg LY2928057 intravenous dose followed by 24-hour observation period; Days 6 and 7: single 1000-mg LY2928057 intravenous dose; Days 8-85: participant follow-up for minimum of 12 weeks to assess the safety, immunogenicity, and pharmacokinetic profile of 1000 mg LY2928057.	Drug: LY2928057; Single intravenous dose.; Other Names: Ferroportin antibody

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Clinically Significant Adverse Effects [Baseline through Day 85]

   A clinically significant effect/event was defined as an adverse event (AE). A listing of serious and non-serious AEs is located in the Reported Adverse Event Module.

Secondary Outcome Measures

1. Pharmacokinetics, Area Under the Curve (AUC) [Predose, end of infusion, 4, 12, and 24 hours post-infusion on Days 3, 5, 8, 11, 15, 22, 29, 43, 50, 57, 64, 71, and 85]

   Area under the LY2928057 plasma concentration-time curve extrapolated to infinite time (AUC0-∞).

2. Pharmacokinetics, Maximum Concentration (Cmax) [Predose, end of infusion, 4, 12, and 24 hours post-infusion on Days 3, 5, 8, 11, 15, 22, 29, 43, 50, 57, 64, 71, and 85]

3. Pharmacokinetics, Time to Maximum Concentration (Tmax) [Predose, end of infusion, 4, 12, and 24 hours post-infusion on Days 3, 5, 8, 11, 15, 22, 29, 43, 50, 57, 64, 71, and 85]

4. Pharmacokinetics, Systemic Clearance (CL) [Predose, end of infusion, 4, 12, and 24 hours post-infusion on Days 3, 5, 8, 11, 15, 22, 29, 43, 50, 57, 64, 71, and 85]

   CL=total body clearance of LY2928057 calculated after intravenous administration. Systemic CL was derived from LY2928057 serum concentration data following intravenous administration using classical non compartmental analysis (WinNonlin version 5.3).

5. Pharmacokinetics, Volume of Distribution (V) [Predose, end of infusion, 4, 12, and 24 hours post-infusion on Days 3, 5, 8, 11, 15, 22, 29, 43, 50, 57, 64, 71, and 85]

   V=LY2928057 steady-state volume of distribution (Vss)

6. Pharmacokinetics, Terminal Half-Life (t1/2) [Predose, end of infusion, 4, 12, and 24 hours post-infusion on Days 3, 5, 8, 11, 15, 22, 29, 43, 50, 57, 64, 71, and 85]

7. Change From Baseline in Serum Iron [Baseline, end of infusion, 4, 12, and 24 hours post-infusion on Days 3, 5, 8, 11, 15 and 22]

   Maximum change from baseline to any point over 22 days post-infusion.

8. Number of Participants Forming Antibody to LY2928057 [Baseline through Day 85]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Must either be a healthy male (and willing to use reliable birth control method during the study and for 3 months following last study drug dose), or a healthy female who cannot become pregnant

• Must have a body mass index (BMI) between 18.5 and 32.0 kilograms per square meter (kg/m^2), inclusive, and a minimum body weight of 55 kg

• Must have acceptable blood and urine laboratory test results for the study

• Must have suitable veins suitable for easy blood collection and study drug administration

• Must be reliable, follow study procedures, and willing to be available for the duration of the study

• Must have given written informed consent

• Must have acceptable blood pressure and pulse rate for the study

Exclusion Criteria:

• Blood test shows that participant has anemia due to lack of iron

• Currently participating in another clinical study or has completed one less than 30 days ago

• Allergic to biologic agents

• Have previously taken part in this study

• Have abnormal electrocardiogram (ECG) findings that suggest an increased risk with study participation

• Have a history of significant disease that may affect drug actions or pose risk when taking study medication

• Have a history of drug or alcohol abuse

• Are infected with human immunodeficiency virus (HIV)

• Have hepatitis B

• Are pregnant or breastfeeding

• Intend to use over-the-counter or prescription medication within 14 days before dosing, other than oestrogen/progesterone as hormone replacement therapy (HRT). Participants taking these medications are expected to be on chronic, stable doses. Certain medications (for example, vitamin supplements) may be permitted at the discretion of the investigator.

• Have donated more than 450 milliliter (mL) of blood within the last 3 months

• Have a regular alcohol intake greater than 21 units per week (male), or 14 units per week (female), or are unwilling to stop alcohol as required for the study (1 unit = 360 mL of beer, 150 mL of wine, or 45 mL of spirits)

• Are a smoker (smoking more than 10 cigarettes per day) or have used equivalent tobacco products. Participants will not be allowed to smoke while in the study unit.

• Have received live vaccine(s) within 1 month of screening, or intend to during the study

• Have received treatment with biologic agents (such as monoclonal antibodies) within 3 months or 5 half-lives (whichever is longer) before receiving study drug in this study

• Have a history of atopy, significant allergies to humanized monoclonal antibodies, clinically significant multiple or severe drug allergies, intolerance to topical corticosteroids, or severe post-treatment hypersensitivity reactions (including, but not limited to, erythema multiforme major, linear immunoglobulin A [IgA] dermatosis, toxic epidermal necrolysis, and exfoliative dermatitis)

• Have any active mental health illness

• Study doctor does not feel the participant should be in the study for any reason

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Singapore		Singapore

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)

None provided.

More Information

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT01330953
• Other Study ID Numbers: 14151; I5M-FW-FABA
• First Posted: Apr 7, 2011
• Last Update Posted: Jul 30, 2018
• Last Verified: Oct 1, 2017

• Keywords provided by Eli Lilly and Company: Anemia

Study Results

Participant Flow

Arm/Group Title	Placebo	30 mg LY2928057	100 mg LY2928057	300 mg LY2928057	1000 mg LY2928057
Arm/Group Description	Single intravenous placebo dose.	Day 1: single 30-mg LY2928057 intravenous dose; Days 2 and 3: observation period; Days 4 and 5: single 30-mg LY2928057 intravenous dose followed by 24-hour observation period; Days 6 and 7: single 30-mg LY2928057 intravenous dose; Days 8-85: participant follow-up for minimum of 12 weeks to assess the safety, immunogenicity, and pharmacokinetic profile of 30 mg LY2928057.	Day 1: single 100-mg LY2928057 intravenous dose; Days 2 and 3: observation period; Days 4 and 5: single 100-mg LY2928057 intravenous dose followed by 24-hour observation period; Days 6 and 7: single 100-mg LY2928057 intravenous dose; Days 8-85: participant follow-up for minimum of 12 weeks to assess the safety, immunogenicity, and pharmacokinetic profile of 100 mg LY2928057.	Day 1: single 300-mg LY2928057 intravenous dose; Days 2 and 3: observation period; Days 4 and 5: 1 participant receives single 300-mg LY2928057 intravenous dose followed by 24-hour observation period; Days 6 and 7: single 300-mg LY2928057 intravenous dose; Days 8-85: participant follow-up for minimum of 12 weeks to assess the safety, immunogenicity, and pharmacokinetic profile of 300 mg LY2928057.	Day 1: single 1000-mg LY2928057 intravenous dose; Days 2 and 3: observation period; Days 4 and 5: single 1000-mg LY2928057 intravenous dose followed by 24-hour observation period; Days 6 and 7: single 1000-mg LY2928057 intravenous dose; Days 8-85: participant follow-up for minimum of 12 weeks to assess the safety, immunogenicity, and pharmacokinetic profile of 1000 mg LY2928057.
Period Title: Overall Study
STARTED	8	6	6	6	6
COMPLETED	8	6	6	6	6
NOT COMPLETED	0	0	0	0	0

Baseline Characteristics

Arm/Group Title	Placebo	30 mg LY2928057	100 mg LY2928057	300 mg LY2928057	1000 mg LY2928057	Total
Arm/Group Description	Single intravenous placebo dose.	Day 1: single 30-mg LY2928057 intravenous dose; Days 2 and 3: observation period; Days 4 and 5: single 30-mg LY2928057 intravenous dose followed by 24-hour observation period; Days 6 and 7: single 30-mg LY2928057 intravenous dose; Days 8-85: participant follow-up for minimum of 12 weeks to assess the safety, immunogenicity, and pharmacokinetic profile of 30 mg LY2928057.	Day 1: single 100-mg LY2928057 intravenous dose; Days 2 and 3: observation period; Days 4 and 5: single 100-mg LY2928057 intravenous dose followed by 24-hour observation period; Days 6 and 7: single 100-mg LY2928057 intravenous dose; Days 8-85: participant follow-up for minimum of 12 weeks to assess the safety, immunogenicity, and pharmacokinetic profile of 100 mg LY2928057.	Day 1: single 300-mg LY2928057 intravenous dose; Days 2 and 3: observation period; Days 4 and 5: 1 participant receives single 300-mg LY2928057 intravenous dose followed by 24-hour observation period; Days 6 and 7: single 300-mg LY2928057 intravenous dose; Days 8-85: participant follow-up for minimum of 12 weeks to assess the safety, immunogenicity, and pharmacokinetic profile of 300 mg LY2928057.	Day 1: single 1000-mg LY2928057 intravenous dose; Days 2 and 3: observation period; Days 4 and 5: single 1000-mg LY2928057 intravenous dose followed by 24-hour observation period; Days 6 and 7: single 1000-mg LY2928057 intravenous dose; Days 8-85: participant follow-up for minimum of 12 weeks to assess the safety, immunogenicity, and pharmacokinetic profile of 1000 mg LY2928057.	Total of all reporting groups
Overall Participants	8	6	6	6	6	32
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	36.0 (13.8)	33.5 (14.8)	31.0 (6.3)	40.2 (11.7)	27.0 (6.1)	33.7 (11.5)
Sex: Female, Male (Count of Participants)
Female	1 12.5%	0 0%	0 0%	0 0%	0 0%	1 3.1%
Male	7 87.5%	6 100%	6 100%	6 100%	6 100%	31 96.9%
Race/Ethnicity, Customized (participants) [Number]
Asian	8 100%	6 100%	6 100%	6 100%	6 100%	32 100%
Region of Enrollment (Count of Participants)
Singapore	8 100%	6 100%	6 100%	6 100%	6 100%	32 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Clinically Significant Adverse Effects
Description	A clinically significant effect/event was defined as an adverse event (AE). A listing of serious and non-serious AEs is located in the Reported Adverse Event Module.
Time Frame	Baseline through Day 85

Outcome Measure Data

Analysis Population Description

The analysis population included all randomized participants dosed with placebo or LY2928057, and who provided safety data at least up to and including the Day 8 assessment.

Arm/Group Title	Placebo	30 mg LY2928057	100 mg LY2928057	300 mg LY2928057	1000 mg LY2928057
Arm/Group Description	Single intravenous placebo dose.	Day 1: single 30-mg LY2928057 intravenous dose; Days 2 and 3: observation period; Days 4 and 5: single 30-mg LY2928057 intravenous dose followed by 24-hour observation period; Days 6 and 7: single 30-mg LY2928057 intravenous dose; Days 8-85: participant follow-up for minimum of 12 weeks to assess the safety, immunogenicity, and pharmacokinetic profile of 30 mg LY2928057.	Day 1: single 100-mg LY2928057 intravenous dose; Days 2 and 3: observation period; Days 4 and 5: single 100-mg LY2928057 intravenous dose followed by 24-hour observation period; Days 6 and 7: single 100-mg LY2928057 intravenous dose; Days 8-85: participant follow-up for minimum of 12 weeks to assess the safety, immunogenicity, and pharmacokinetic profile of 100 mg LY2928057.	Day 1: single 300-mg LY2928057 intravenous dose; Days 2 and 3: observation period; Days 4 and 5: 1 participant receives single 300-mg LY2928057 intravenous dose followed by 24-hour observation period; Days 6 and 7: single 300-mg LY2928057 intravenous dose; Days 8-85: participant follow-up for minimum of 12 weeks to assess the safety, immunogenicity, and pharmacokinetic profile of 300 mg LY2928057.	Day 1: single 1000-mg LY2928057 intravenous dose; Days 2 and 3: observation period; Days 4 and 5: single 1000-mg LY2928057 intravenous dose followed by 24-hour observation period; Days 6 and 7: single 1000-mg LY2928057 intravenous dose; Days 8-85: participant follow-up for minimum of 12 weeks to assess the safety, immunogenicity, and pharmacokinetic profile of 1000 mg LY2928057.
Measure Participants	8	6	6	6	6
Number [participants]	7 87.5%	6 100%	5 83.3%	5 83.3%	6 100%

2. Secondary Outcome

Title	Pharmacokinetics, Area Under the Curve (AUC)
Description	Area under the LY2928057 plasma concentration-time curve extrapolated to infinite time (AUC0-∞).
Time Frame	Predose, end of infusion, 4, 12, and 24 hours post-infusion on Days 3, 5, 8, 11, 15, 22, 29, 43, 50, 57, 64, 71, and 85

Outcome Measure Data

Analysis Population Description

The analysis population included all randomized participants who received at least 1 dose of LY2928057 and provided samples for pharmacokinetic AUC analyses.

Arm/Group Title	30 mg LY2928057	100 mg LY2928057	300 mg LY2928057	1000 mg LY2928057
Arm/Group Description	Day 1: single 30-mg LY2928057 intravenous dose; Days 2 and 3: observation period; Days 4 and 5: single 30-mg LY2928057 intravenous dose followed by 24-hour observation period; Days 6 and 7: single 30-mg LY2928057 intravenous dose; Days 8-85: participant follow-up for minimum of 12 weeks to assess the safety, immunogenicity, and pharmacokinetic profile of 30 mg LY2928057.	Day 1: single 100-mg LY2928057 intravenous dose; Days 2 and 3: observation period; Days 4 and 5: single 100-mg LY2928057 intravenous dose followed by 24-hour observation period; Days 6 and 7: single 100-mg LY2928057 intravenous dose; Days 8-85: participant follow-up for minimum of 12 weeks to assess the safety, immunogenicity, and pharmacokinetic profile of 100 mg LY2928057.	Day 1: single 300-mg LY2928057 intravenous dose; Days 2 and 3: observation period; Days 4 and 5: 1 participant receives single 300-mg LY2928057 intravenous dose followed by 24-hour observation period; Days 6 and 7: single 300-mg LY2928057 intravenous dose; Days 8-85: participant follow-up for minimum of 12 weeks to assess the safety, immunogenicity, and pharmacokinetic profile of 300 mg LY2928057.	Day 1: single 1000-mg LY2928057 intravenous dose; Days 2 and 3: observation period; Days 4 and 5: single 1000-mg LY2928057 intravenous dose followed by 24-hour observation period; Days 6 and 7: single 1000-mg LY2928057 intravenous dose; Days 8-85: participant follow-up for minimum of 12 weeks to assess the safety, immunogenicity, and pharmacokinetic profile of 1000 mg LY2928057.
Measure Participants	6	6	6	6
Geometric Mean (Geometric Coefficient of Variation) [nanogram*hour per milliliter (ng*h/mL)]	45500 (53)	1000000 (23)	4060000 (40)	19700000 (28)

3. Secondary Outcome

Title	Pharmacokinetics, Maximum Concentration (Cmax)
Time Frame	Predose, end of infusion, 4, 12, and 24 hours post-infusion on Days 3, 5, 8, 11, 15, 22, 29, 43, 50, 57, 64, 71, and 85

Outcome Measure Data

Analysis Population Description

The analysis population included all randomized participants who received at least 1 dose of LY2928057 and provided samples for pharmacokinetic Cmax analyses.

Arm/Group Title	30 mg LY2928057	100 mg LY2928057	300 mg LY2928057	1000 mg LY2928057
Arm/Group Description	Day 1: single 30-mg LY2928057 intravenous dose; Days 2 and 3: observation period; Days 4 and 5: single 30-mg LY2928057 intravenous dose followed by 24-hour observation period; Days 6 and 7: single 30-mg LY2928057 intravenous dose; Days 8-85: participant follow-up for minimum of 12 weeks to assess the safety, immunogenicity, and pharmacokinetic profile of 30 mg LY2928057.	Day 1: single 100-mg LY2928057 intravenous dose; Days 2 and 3: observation period; Days 4 and 5: single 100-mg LY2928057 intravenous dose followed by 24-hour observation period; Days 6 and 7: single 100-mg LY2928057 intravenous dose; Days 8-85: participant follow-up for minimum of 12 weeks to assess the safety, immunogenicity, and pharmacokinetic profile of 100 mg LY2928057.	Day 1: single 300-mg LY2928057 intravenous dose; Days 2 and 3: observation period; Days 4 and 5: 1 participant receives single 300-mg LY2928057 intravenous dose followed by 24-hour observation period; Days 6 and 7: single 300-mg LY2928057 intravenous dose; Days 8-85: participant follow-up for minimum of 12 weeks to assess the safety, immunogenicity, and pharmacokinetic profile of 300 mg LY2928057.	Day 1: single 1000-mg LY2928057 intravenous dose; Days 2 and 3: observation period; Days 4 and 5: single 1000-mg LY2928057 intravenous dose followed by 24-hour observation period; Days 6 and 7: single 1000-mg LY2928057 intravenous dose; Days 8-85: participant follow-up for minimum of 12 weeks to assess the safety, immunogenicity, and pharmacokinetic profile of 1000 mg LY2928057.
Measure Participants	6	6	6	6
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	4560 (21)	27400 (14)	88500 (19)	276000 (22)

4. Secondary Outcome

Title	Pharmacokinetics, Time to Maximum Concentration (Tmax)
Time Frame	Predose, end of infusion, 4, 12, and 24 hours post-infusion on Days 3, 5, 8, 11, 15, 22, 29, 43, 50, 57, 64, 71, and 85

Outcome Measure Data

Analysis Population Description

The analysis population included all randomized participants who received at least 1 dose of LY2928057 and provided samples for pharmacokinetic tmax analyses.

Arm/Group Title	30 mg LY2928057	100 mg LY2928057	300 mg LY2928057	1000 mg LY2928057
Arm/Group Description	Day 1: single 30-mg LY2928057 intravenous dose; Days 2 and 3: observation period; Days 4 and 5: single 30-mg LY2928057 intravenous dose followed by 24-hour observation period; Days 6 and Day 7: single 30-mg LY2928057 intravenous dose; Days 8-85: participant follow-up for minimum of 12 weeks to assess the safety, immunogenicity, and pharmacokinetic profile of 30 mg LY2928057.	Day 1: single 100-mg LY2928057 intravenous dose; Days 2 and 3: observation period; Days 4 and 5: single 100-mg LY2928057 intravenous dose followed by 24-hour observation period; Days 6 and 7: single 100-mg LY2928057 intravenous dose; Days 8-85: participant follow-up for minimum of 12 weeks to assess the safety, immunogenicity, and pharmacokinetic profile of 100 mg LY2928057.	Day 1: single 300-mg LY2928057 intravenous dose; Days 2 and 3: observation period; Days 4 and 5: 1 participant receives single 300-mg LY2928057 intravenous dose followed by 24-hour observation period; Days 6 and 7: single 300-mg LY2928057 intravenous dose; Days 8-85: participant follow-up for minimum of 12 weeks to assess the safety, immunogenicity, and pharmacokinetic profile of 300 mg LY2928057.	Day 1: single 1000-mg LY2928057 intravenous dose; Days 2 and 3: observation period; Days 4 and 5: single 1000-mg LY2928057 intravenous dose followed by 24-hour observation period; Days 6 and 7: single 1000-mg LY2928057 intravenous dose; Days 8-85: participant follow-up for minimum of 12 weeks to assess the safety, immunogenicity, and pharmacokinetic profile of 1000 mg LY2928057.
Measure Participants	6	6	6	6
Median (Full Range) [hour (h)]	0.50	0.50	0.50	0.50

5. Secondary Outcome

Title	Pharmacokinetics, Systemic Clearance (CL)
Description	CL=total body clearance of LY2928057 calculated after intravenous administration. Systemic CL was derived from LY2928057 serum concentration data following intravenous administration using classical non compartmental analysis (WinNonlin version 5.3).
Time Frame	Predose, end of infusion, 4, 12, and 24 hours post-infusion on Days 3, 5, 8, 11, 15, 22, 29, 43, 50, 57, 64, 71, and 85

Outcome Measure Data

Analysis Population Description

The analysis population included all randomized participants who received at least 1 dose of LY2928057 and provided samples for pharmacokinetic systemic CL analyses.

Arm/Group Title	30 mg LY2928057	100 mg LY2928057	300 mg LY2928057	1000 mg LY2928057
Arm/Group Description	Day 1: single 30-mg LY2928057 intravenous dose; Days 2 and 3: observation period; Days 4 and 5: single 30-mg LY2928057 intravenous dose followed by 24-hour observation period; Days 6 and 7: single 30-mg LY2928057 intravenous dose; Days 8-85: participant follow-up for minimum of 12 weeks to assess the safety, immunogenicity, and pharmacokinetic profile of 30 mg LY2928057.	Day 1: single 100-mg LY2928057 intravenous dose; Days 2 and 3: observation period; Days 4 and 5: single 100-mg LY2928057 intravenous dose followed by 24-hour observation period; Days 6 and 7: single 100-mg LY2928057 intravenous dose; Days 8-85: participant follow-up for minimum of 12 weeks to assess the safety, immunogenicity, and pharmacokinetic profile of 100 mg LY2928057.	Day 1: single 300-mg LY2928057 intravenous dose; Days 2 and 3: observation period; Days 4 and 5: 1 participant receives single 300-mg LY2928057 intravenous dose followed by 24-hour observation period; Days 6 and 7: single 300-mg LY2928057 intravenous dose; Days 8-85: participant follow-up for minimum of 12 weeks to assess the safety, immunogenicity, and pharmacokinetic profile of 300 mg LY2928057.	Day 1: single 1000-mg LY2928057 intravenous dose; Days 2 and 3: observation period; Days 4 and 5: single 1000-mg LY2928057 intravenous dose followed by 24-hour observation period; Days 6 and 7: single 1000-mg LY2928057 intravenous dose; Days 8-85: participant follow-up for minimum of 12 weeks to assess the safety, immunogenicity, and pharmacokinetic profile of 1000 mg LY2928057.
Measure Participants	6	6	6	6
Geometric Mean (Geometric Coefficient of Variation) [liter per hour (L/h)]	0.6590 (53)	0.0999 (23)	0.0739 (40)	0.0507 (28)

6. Secondary Outcome

Title	Pharmacokinetics, Volume of Distribution (V)
Description	V=LY2928057 steady-state volume of distribution (Vss)
Time Frame	Predose, end of infusion, 4, 12, and 24 hours post-infusion on Days 3, 5, 8, 11, 15, 22, 29, 43, 50, 57, 64, 71, and 85

Outcome Measure Data

Analysis Population Description

The analysis population included all randomized participants who received at least 1 dose of LY2928057 and provided samples for pharmacokinetic Vss analyses.

Arm/Group Title	30 mg LY2928057	100 mg LY2928057	300 mg LY2928057	1000 mg LY2928057
Arm/Group Description	Day 1: single 30-mg LY2928057 intravenous dose; Days 2 and 3: observation period; Days 4 and 5: single 30-mg LY2928057 intravenous dose followed by 24-hour observation period; Days 6 and 7: single 30-mg LY2928057 intravenous dose; Days 8-85: participant follow-up for minimum of 12 weeks to assess the safety, immunogenicity, and pharmacokinetic profile of 30 mg LY2928057.	Day 1: single 100-mg LY2928057 intravenous dose; Days 2 and 3: observation period; Days 4 and 5: single 100-mg LY2928057 intravenous dose followed by 24-hour observation period; Days 6 and 7: single 100-mg LY2928057 intravenous dose; Days 8-85: participant follow-up for minimum of 12 weeks to assess the safety, immunogenicity, and pharmacokinetic profile of 100 mg LY2928057.	Day 1: single 300-mg LY2928057 intravenous dose; Days 2 and 3: observation period; Days 4 and 5: 1 participant receives single 300-mg LY2928057 intravenous dose followed by 24-hour observation period; Days 6 and 7: single 300-mg LY2928057 intravenous dose; Days 8-85: participant follow-up for minimum of 12 weeks to assess the safety, immunogenicity, and pharmacokinetic profile of 300 mg LY2928057.	Day 1: single 1000-mg LY2928057 intravenous dose; Days 2 and 3: observation period; Days 4 and 5: single 1000-mg LY2928057 intravenous dose followed by 24-hour observation period; Days 6 and 7: single 1000-mg LY2928057 intravenous dose; Days 8-85: participant follow-up for minimum of 12 weeks to assess the safety, immunogenicity, and pharmacokinetic profile of 1000 mg LY2928057.
Measure Participants	6	6	6	6
Geometric Mean (Geometric Coefficient of Variation) [L]	13.80 (46)	4.01 (19)	3.82 (19)	4.69 (22)

7. Secondary Outcome

Title	Pharmacokinetics, Terminal Half-Life (t1/2)
Time Frame	Predose, end of infusion, 4, 12, and 24 hours post-infusion on Days 3, 5, 8, 11, 15, 22, 29, 43, 50, 57, 64, 71, and 85

Outcome Measure Data

Analysis Population Description

The analysis population included all randomized participants who received at least 1 dose of LY2928057 and provided samples for pharmacokinetic t1/2 analyses.

Arm/Group Title	30 mg LY2928057	100 mg LY2928057	300 mg LY2928057	1000 mg LY2928057
Arm/Group Description	Day 1: single 30-mg LY2928057 intravenous dose; Days 2 and 3: observation period; Days 4 and 5: single 30-mg LY2928057 intravenous dose followed by 24-hour observation period; Days 6 and 7: single 30-mg LY2928057 intravenous dose; Days 8-85: participant follow-up for minimum of 12 weeks to assess the safety, immunogenicity, and pharmacokinetic profile of 30 mg LY2928057.	Day 1: single 100-mg LY2928057 intravenous dose; Days 2 and 3: observation period; Days 4 and 5: single 100-mg LY2928057 intravenous dose followed by 24-hour observation period; Days 6 and 7: single 100-mg LY2928057 intravenous dose; Days 8-85: participant follow-up for minimum of 12 weeks to assess the safety, immunogenicity, and pharmacokinetic profile of 100 mg LY2928057.	Day 1: single 300-mg LY2928057 intravenous dose; Days 2 and 3: observation period; Days 4 and 5: 1 participant receives single 300-mg LY2928057 intravenous dose followed by 24-hour observation period; Days 6 and 7: single 300-mg LY2928057 intravenous dose; Days 8-85: participant follow-up for minimum of 12 weeks to assess the safety, immunogenicity, and pharmacokinetic profile of 300 mg LY2928057.	Day 1: single 1000-mg LY2928057 intravenous dose; Days 2 and 3: observation period; Days 4 and 5: single 1000-mg LY2928057 intravenous dose followed by 24-hour observation period; Days 6 and 7: single 1000-mg LY2928057 intravenous dose; Days 8-85: participant follow-up for minimum of 12 weeks to assess the safety, immunogenicity, and pharmacokinetic profile of 1000 mg LY2928057.
Measure Participants	6	6	6	6
Geometric Mean (Full Range) [days]	1.2	5.1	6.6	10.3

8. Secondary Outcome

Title	Change From Baseline in Serum Iron
Description	Maximum change from baseline to any point over 22 days post-infusion.
Time Frame	Baseline, end of infusion, 4, 12, and 24 hours post-infusion on Days 3, 5, 8, 11, 15 and 22

Outcome Measure Data

Analysis Population Description

The analysis population included all randomized participants who received at least 1 dose of LY2928057 and provided plasma data for measuring serum iron levels as the primary pharmacodynamic analysis.

Arm/Group Title	Placebo	30 mg LY2928057	100 mg LY2928057	300 mg LY2928057	1000 mg LY2928057
Arm/Group Description	Single intravenous placebo dose.	Day 1: single 30-mg LY2928057 intravenous dose; Days 2 and 3: observation period; Days 4 and 5: single 30-mg LY2928057 intravenous dose followed by 24-hour observation period; Days 6 and 7: single 30-mg LY2928057 intravenous dose; Days 8-85: participant follow-up for minimum of 12 weeks to assess the safety, immunogenicity, and pharmacokinetic profile of 30 mg LY2928057.	Day 1: single 100-mg LY2928057 intravenous dose; Days 2 and 3: observation period; Days 4 and 5: single 100-mg LY2928057 intravenous dose followed by 24-hour observation period; Days 6 and 7: single 100-mg LY2928057 intravenous dose; Days 8-85: participant follow-up for minimum of 12 weeks to assess the safety, immunogenicity, and pharmacokinetic profile of 100 mg LY2928057.	Day 1: single 300-mg LY2928057 intravenous dose; Days 2 and 3: observation period; Days 4 and 5: 1 participant receives single 300-mg LY2928057 intravenous dose followed by 24-hour observation period; Days 6 and 7: single 300-mg LY2928057 intravenous dose; Days 8-85: participant follow-up for minimum of 12 weeks to assess the safety, immunogenicity, and pharmacokinetic profile of 300 mg LY2928057.	Day 1: single 1000-mg LY2928057 intravenous dose; Days 2 and 3: observation period; Days 4 and 5: single 1000-mg LY2928057 intravenous dose followed by 24-hour observation period; Days 6 and 7: single 1000-mg LY2928057 intravenous dose; Days 8-85: participant follow-up for minimum of 12 weeks to assess the safety, immunogenicity, and pharmacokinetic profile of 1000 mg LY2928057.
Measure Participants	8	6	6	6	6
Mean (Standard Deviation) [microgram per deciliter (µg/dL)]	32.9 (17.5)	71.9 (36.1)	59.9 (22.4)	95.1 (49.8)	96.3 (51.9)

9. Secondary Outcome

Title	Number of Participants Forming Antibody to LY2928057
Time Frame	Baseline through Day 85

Outcome Measure Data

Analysis Population Description

The analysis population included all randomized participants who received at least 1 dose of LY2928057 and antibody titer results.

Arm/Group Title	Placebo	30 mg LY2928057	100 mg LY2928057	300 mg LY2928057	1000 mg LY2928057
Arm/Group Description	Single intravenous placebo dose.	Day 1: single 30-mg LY2928057 intravenous dose; Days 2 and 3: observation period; Days 4 and 5: single 30-mg LY2928057 intravenous dose followed by 24-hour observation period; Days 6 and 7: single 30-mg LY2928057 intravenous dose; Days 8-85: participant follow-up for minimum of 12 weeks to assess the safety, immunogenicity, and pharmacokinetic profile of 30 mg LY2928057.	Day 1: single 100-mg LY2928057 intravenous dose; Days 2 and 3: observation period; Days 4 and 5: single 100-mg LY2928057 intravenous dose followed by 24-hour observation period; Days 6 and 7: single 100-mg LY2928057 intravenous dose; Days 8-85: participant follow-up for minimum of 12 weeks to assess the safety, immunogenicity, and pharmacokinetic profile of 100 mg LY2928057.	Day 1: single 300-mg LY2928057 intravenous dose; Days 2 and 3: observation period; Days 4 and 5: 1 participant receives single 300-mg LY2928057 intravenous dose followed by 24-hour observation period; Days 6 and 7: single 300-mg LY2928057 intravenous dose; Days 8-85: participant follow-up for minimum of 12 weeks to assess the safety, immunogenicity, and pharmacokinetic profile of 300 mg LY2928057.	Day 1: single 1000-mg LY2928057 intravenous dose; Days 2 and 3: observation period; Days 4 and 5: single 1000-mg LY2928057 intravenous dose followed by 24-hour observation period; Days 6 and 7: single 1000-mg LY2928057 intravenous dose; Days 8-85: participant follow-up for minimum of 12 weeks to assess the safety, immunogenicity, and pharmacokinetic profile of 1000 mg LY2928057.
Measure Participants	8	6	6	6	6
Number [participants]	0 0%	3 50%	2 33.3%	5 83.3%	4 66.7%

Adverse Events

Arm/Group Title	Placebo		30 mg LY2928057		100 mg LY2928057		300 mg LY2928057		1000 mg LY2928057
Arm/Group Description	Single intravenous placebo dose.		Day 1: single 30-mg LY2928057 intravenous dose; Days 2 and 3: observation period; Days 4 and 5: single 30-mg LY2928057 intravenous dose followed by 24-hour observation period; Days 6 and 7: single 30-mg LY2928057 intravenous dose; Days 8-85: participant follow-up for minimum of 12 weeks to assess the safety, immunogenicity, and pharmacokinetic profile of 30 mg LY2928057.		Day 1: single 100-mg LY2928057 intravenous dose; Days 2 and 3: observation period; Days 4 and 5: single 100-mg LY2928057 intravenous dose followed by 24-hour observation period; Days 6 and 7: single 100-mg LY2928057 intravenous dose; Days 8-85: participant follow-up for minimum of 12 weeks to assess the safety, immunogenicity, and pharmacokinetic profile of 100 mg LY2928057.		Day 1: single 300-mg LY2928057 intravenous dose; Days 2 and 3: observation period; Days 4 and 5: 1 participant receives single 300-mg LY2928057 intravenous dose followed by 24-hour observation period; Days 6 and 7: single 300-mg LY2928057 intravenous dose; Days 8-85: participant follow-up for minimum of 12 weeks to assess the safety, immunogenicity, and pharmacokinetic profile of 300 mg LY2928057.		Day 1: single 1000-mg LY2928057 intravenous dose; Days 2 and 3: observation period; Days 4 and 5: single 1000-mg LY2928057 intravenous dose followed by 24-hour observation period; Days 6 and 7: single 1000-mg LY2928057 intravenous dose; Days 8-85: participant follow-up for minimum of 12 weeks to assess the safety, immunogenicity, and pharmacokinetic profile of 1000 mg LY2928057.
All Cause Mortality
	Placebo		30 mg LY2928057		100 mg LY2928057		300 mg LY2928057		1000 mg LY2928057
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		30 mg LY2928057		100 mg LY2928057		300 mg LY2928057		1000 mg LY2928057
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		30 mg LY2928057		100 mg LY2928057		300 mg LY2928057		1000 mg LY2928057
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/8 (87.5%)		6/6 (100%)		5/6 (83.3%)		5/6 (83.3%)		6/6 (100%)
Eye disorders
Conjunctival hyperaemia	0/8 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0
Eye swelling	0/8 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0
Gastrointestinal disorders
Diarrhoea	0/8 (0%)	0	1/6 (16.7%)	1	1/6 (16.7%)	1	0/6 (0%)	0	1/6 (16.7%)	1
Mouth ulceration	1/8 (12.5%)	1	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0
General disorders
Application site erythema	0/8 (0%)	0	0/6 (0%)	0	2/6 (33.3%)	3	0/6 (0%)	0	0/6 (0%)	0
Catheter site pain	0/8 (0%)	0	4/6 (66.7%)	4	1/6 (16.7%)	1	2/6 (33.3%)	2	0/6 (0%)	0
Catheter site related reaction	1/8 (12.5%)	2	5/6 (83.3%)	7	3/6 (50%)	5	2/6 (33.3%)	4	4/6 (66.7%)	6
Fatigue	1/8 (12.5%)	1	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0
Infusion site erythema	1/8 (12.5%)	1	1/6 (16.7%)	1	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0
Infusion site haematoma	0/8 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0
Pain	1/8 (12.5%)	1	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0
Pyrexia	1/8 (12.5%)	1	1/6 (16.7%)	1	1/6 (16.7%)	1	1/6 (16.7%)	1	1/6 (16.7%)	1
Vessel puncture site haematoma	1/8 (12.5%)	2	1/6 (16.7%)	1	1/6 (16.7%)	1	1/6 (16.7%)	2	1/6 (16.7%)	1
Vessel puncture site reaction	1/8 (12.5%)	1	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0
Infections and infestations
Furuncle	0/8 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0
Herpes zoster	0/8 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1
Influenza	0/8 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0
Tinea versicolour	0/8 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0
Injury, poisoning and procedural complications
Skin laceration	2/8 (25%)	2	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0
Thermal burn	1/8 (12.5%)	1	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0
Musculoskeletal and connective tissue disorders
Back pain	0/8 (0%)	0	2/6 (33.3%)	3	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0
Musculoskeletal chest pain	0/8 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0
Nervous system disorders
Dizziness	0/8 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1
Headache	2/8 (25%)	2	1/6 (16.7%)	1	0/6 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0
Respiratory, thoracic and mediastinal disorders
Cough	0/8 (0%)	0	2/6 (33.3%)	3	2/6 (33.3%)	4	1/6 (16.7%)	1	1/6 (16.7%)	1
Nasal congestion	1/8 (12.5%)	1	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0
Oropharyngeal pain	1/8 (12.5%)	1	2/6 (33.3%)	2	2/6 (33.3%)	2	0/6 (0%)	0	1/6 (16.7%)	1
Rhinorrhoea	1/8 (12.5%)	1	1/6 (16.7%)	1	1/6 (16.7%)	1	2/6 (33.3%)	4	0/6 (0%)	0
Skin and subcutaneous tissue disorders
Erythema	0/8 (0%)	0	1/6 (16.7%)	1	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0
Rash	0/8 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	2	1/6 (16.7%)	3	0/6 (0%)	0
Rash generalised	0/8 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0	1/6 (16.7%)	1
Rash maculo-papular	0/8 (0%)	0	1/6 (16.7%)	2	0/6 (0%)	0	0/6 (0%)	0	0/6 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT 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.