Kidney Disease, Chronic, Renal Insufficiency, Chronic
Conditions
Brief summary
This study will evaluate the safety of LY2928057 and how LY2928057 affects hemoglobin in hemodialysis participants. This study will involve multiple doses of LY2928057 given during a 6 week period either after a participant discontinues or reduces treatment to stimulate red blood cells. This study will last up to 26 weeks for each participant.
Interventions
DRUGLY2928057
Administered intravenously
DRUGPlacebo
Administered intravenously
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participants having end-stage renal disease (ESRD), have received an erythropoiesis stimulating agent (ESA) at least weekly for 2 weeks prior to screening, and have been receiving adequate maintenance hemodialysis (3 times weekly) for at least 12 weeks prior to screening (that is, an approximate Kt/V greater than 1.1 (K equals dialyzer clearance of urea, t equals dialysis duration time, V equals volume of distribution of urea, which is approximately equal to the participant's total body water) based on the clinical judgment of participant's nephrologist and investigator and who are willing to stop (Parts A and B) or reduce (Part C) their stable ESA dose from the week of randomization until completion of the 6-week treatment period (unless rescue therapy is needed) * Have a hemoglobin value (taken prior to dialysis if taken on a dialysis day) greater than or equal to 9.5 grams per deciLiter (g/dL) and less than or equal to 12.5 g/dL at screening * Have a body mass index (BMI) of 18.5 to 45 kilograms per square meter (kg/m\^2) inclusive at screening * Have a transferrin saturation (TSat) greater than or equality to 15 percent and ferritin greater than 40 nanograms per milliliter (ng/mL) at screening
Exclusion criteria
* Any cause of anemia other than renal disease * A history of hyporesponsiveness to ESA
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | Baseline to Study Completion (up to Day 137) | A summary of other nonserious adverse events (AEs) and all SAEs, regardless of causality, is located in the Reported Adverse Events section. |
| Change From Baseline in Hemoglobin at 6 Week Endpoint | Baseline, Day 42 | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacodynamics (PD): Maximum Change in Transferrin Saturation (TSat) | Baseline through 6 weeks | — |
| Pharmacodynamics (PD): Maximum Change in Concentration of Hemoglobin in Reticulocytes (CHr) | Baseline through 6 weeks | — |
| Pharmacodynamics (PD): Maximum Change in Reticulocyte Count | Baseline through 6 weeks | — |
| Pharmacodynamics (PD): Maximum Change in Red Blood Cell (RBC) Count | Baseline through 6 weeks | — |
| Pharmacodynamics (PD): Maximum Change in Mean Corpuscular Volume (MCV) | Baseline through 6 weeks | — |
| Pharmacodynamics (PD): Maximum Change in Mean Corpuscular Hemoglobin (MCH) | Baseline through 6 weeks | — |
| Pharmacodynamics (PD): Maximum Change in Hemoglobin | Baseline through 6 Weeks | — |
| Pharmacodynamics (PD): Maximum Change in Ferritin | Baseline through 6 weeks | — |
| Pharmacokinetics: Maximum Concentration (Cmax) of LY2928057 | Cycle 1: Predose, end of infusion, 2hours(h), 4h, 2d, 4d, 7d, 9d, 11d postdose; | Time frame for Cycle 2: Predose, end of infusion, prior to end of dialysis or 2h, post dialysis or 4h, 2 days (d), 4d, 7d, 9d, 11d postdose; Time frame for Cycle 3: Predose, end of infusion, prior to end of dialysis or 2h, post dialysis or 4h, 2d, 4d, 7d, 9d, 11d, 14d postdose |
| Pharmacokinetics: Area Under the Concentration Curve From Time Zero to Infinity (AUC[0-inf]) of LY2928057 | Cycle 1: Predose, end of infusion, 2hours(h), 4h, 2d, 4d, 7d, 9d, 11d postdose | Time frame for Cycle 2: Predose, end of infusion, prior to end of dialysis or 2h, post dialysis or 4h, 2d, 4d, 7d, 9d, 11d postdose; Time frame for Cycle 3: Predose, end of infusion, prior to end of dialysis or 2h, post dialysis or 4h, 2d, 4d, 7d, 9d, 11d, 14d postdose; |
| Number of Participants With Anti-LY2928057 Antibodies | Baseline through 84 days | — |
| Area Under the Plasma Concentration-Time Curve From 0 to 336 Hours AUC(0-336) During and Outside Dialysis | Cycle 1: Predose, end of infusion, 2hours, 4h, 2d, 4d, 7d, 9d, 11d postdose | Time frame for Cycle 2: Predose, end of infusion, prior to end of dialysis or 2h, post dialysis or 4h, 2d, 4d, 7d, 9d, 11d postdose; Dialysis did not occur in cycle 1. |
| Pharmacodynamics (PD): Maximum Change in Mean Corpuscular Hemoglobin Concentration (MCHC) | Baseline through 6 weeks | — |
| Pharmacodynamics (PD): Geometric Mean Ratio of Serum Iron (Fe) Concentrations Relative to Baseline | Baseline, 6 weeks | Pharmacodynamics (PD): Geometric Mean Ratio of Serum Iron (Fe) Concentrations relative to baseline. |
Countries
United States
Participant flow
Pre-assignment details
This study included three parts. Part A was dose escalation (placebo, 300, 600, or 1,000 milligrams \[mg\] LY2928057). Part B was dose expansion (placebo or 1000 mg LY2928057). Part C was optional, based on predefined pharmacodynamics criteria. Part C was not executed.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo administered IV Q2W for six weeks (three doses). | 7 |
| 300 mg LY2928057 300 mg LY2928057 administered IV Q2W for six weeks (three doses). | 6 |
| 600 mg LY2928057 600 mg LY2928057 administered IV Q2W for six weeks (three doses). | 11 |
| 1000 mg LY2928057 1000 mg LY2928057 administered IV Q2W for six weeks (three doses). | 4 |
| Total | 28 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Dose Level 1000 mg | Protocol Violation | 0 | 0 | 0 | 1 |
| Dose Level 600 mg | Physician Decision | 0 | 0 | 1 | 0 |
| Dose Level 600 mg | Withdrawal by Subject | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo | Total | 1000 mg LY2928057 | 600 mg LY2928057 | 300 mg LY2928057 |
|---|---|---|---|---|---|
| Age, Continuous | 52.1 years STANDARD_DEVIATION 9.1 | 53.6 years STANDARD_DEVIATION 8 | 61.0 years STANDARD_DEVIATION 9.8 | 52.5 years STANDARD_DEVIATION 7.6 | 52.5 years STANDARD_DEVIATION 4.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 3 Participants | 0 Participants | 2 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 25 Participants | 4 Participants | 9 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 19 Participants | 3 Participants | 7 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 9 Participants | 1 Participants | 4 Participants | 1 Participants |
| Region of Enrollment United States | 7 Participants | 28 Participants | 4 Participants | 11 Participants | 6 Participants |
| Sex: Female, Male Female | 2 Participants | 9 Participants | 2 Participants | 3 Participants | 2 Participants |
| Sex: Female, Male Male | 5 Participants | 19 Participants | 2 Participants | 8 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 7 / 7 | 6 / 6 | 8 / 11 | 3 / 4 |
| serious Total, serious adverse events | 0 / 7 | 2 / 6 | 0 / 11 | 1 / 4 |
Outcome results
Primary
Change From Baseline in Hemoglobin at 6 Week Endpoint
Time frame: Baseline, Day 42
Population: All participants who received three doses of study drug, had pharmacodynamics assessment at Week 6, and/or received anti-anemic rescue therapy per protocol, regardless of whether they completed treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Hemoglobin at 6 Week Endpoint | -1.674 grams per deciliter (g/dL) | Standard Deviation 0.5535 |
| 300 mg LY2928057 | Change From Baseline in Hemoglobin at 6 Week Endpoint | -1.739 grams per deciliter (g/dL) | Standard Deviation 0.5261 |
| 600 mg LY2928057 | Change From Baseline in Hemoglobin at 6 Week Endpoint | -0.906 grams per deciliter (g/dL) | Standard Deviation 0.4577 |
| 1000 mg LY2928057 | Change From Baseline in Hemoglobin at 6 Week Endpoint | -1.623 grams per deciliter (g/dL) | Standard Deviation 1.0469 |
Primary
Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration
A summary of other nonserious adverse events (AEs) and all SAEs, regardless of causality, is located in the Reported Adverse Events section.
Time frame: Baseline to Study Completion (up to Day 137)
Population: All participants who received at least one dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | 0 Participants |
| 300 mg LY2928057 | Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | 0 Participants |
| 600 mg LY2928057 | Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | 0 Participants |
| 1000 mg LY2928057 | Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | 0 Participants |
Secondary
Area Under the Plasma Concentration-Time Curve From 0 to 336 Hours AUC(0-336) During and Outside Dialysis
Time frame for Cycle 2: Predose, end of infusion, prior to end of dialysis or 2h, post dialysis or 4h, 2d, 4d, 7d, 9d, 11d postdose; Dialysis did not occur in cycle 1.
Time frame: Cycle 1: Predose, end of infusion, 2hours, 4h, 2d, 4d, 7d, 9d, 11d postdose
Population: All participants who received 300 mg LY2928057 or 600 mg LY2928057 during dialysis and non-dialysis day and had evaluable plasma values. Data were not collected in the 1000 mg LY2928057 arm.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Area Under the Plasma Concentration-Time Curve From 0 to 336 Hours AUC(0-336) During and Outside Dialysis | Cycle 1 (First dose, no dialysis) | 1550 hr*ng/mL | Geometric Coefficient of Variation 39 |
| Placebo | Area Under the Plasma Concentration-Time Curve From 0 to 336 Hours AUC(0-336) During and Outside Dialysis | Cycle 2 (Second dose during dialysis) | 1630 hr*ng/mL | Geometric Coefficient of Variation 42 |
| 300 mg LY2928057 | Area Under the Plasma Concentration-Time Curve From 0 to 336 Hours AUC(0-336) During and Outside Dialysis | Cycle 1 (First dose, no dialysis) | 7320 hr*ng/mL | Geometric Coefficient of Variation 33 |
| 300 mg LY2928057 | Area Under the Plasma Concentration-Time Curve From 0 to 336 Hours AUC(0-336) During and Outside Dialysis | Cycle 2 (Second dose during dialysis) | 6940 hr*ng/mL | Geometric Coefficient of Variation 40 |
Secondary
Number of Participants With Anti-LY2928057 Antibodies
Time frame: Baseline through 84 days
Population: All participants who received at least one dose of study drug and had evaluable antibody values at baseline and post-baseline.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Number of Participants With Anti-LY2928057 Antibodies | 1 participants |
| 300 mg LY2928057 | Number of Participants With Anti-LY2928057 Antibodies | 4 participants |
| 600 mg LY2928057 | Number of Participants With Anti-LY2928057 Antibodies | 6 participants |
| 1000 mg LY2928057 | Number of Participants With Anti-LY2928057 Antibodies | 3 participants |
Secondary
Pharmacodynamics (PD): Geometric Mean Ratio of Serum Iron (Fe) Concentrations Relative to Baseline
Pharmacodynamics (PD): Geometric Mean Ratio of Serum Iron (Fe) Concentrations relative to baseline.
Time frame: Baseline, 6 weeks
Population: All participants who received at least one dose of study drug and had evaluable serum Fe values at baseline and post-baseline.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Pharmacodynamics (PD): Geometric Mean Ratio of Serum Iron (Fe) Concentrations Relative to Baseline | 0.99 Ratio | Geometric Coefficient of Variation 16 |
| 300 mg LY2928057 | Pharmacodynamics (PD): Geometric Mean Ratio of Serum Iron (Fe) Concentrations Relative to Baseline | 1.57 Ratio | Geometric Coefficient of Variation 32 |
| 600 mg LY2928057 | Pharmacodynamics (PD): Geometric Mean Ratio of Serum Iron (Fe) Concentrations Relative to Baseline | 1.59 Ratio | Geometric Coefficient of Variation 69 |
| 1000 mg LY2928057 | Pharmacodynamics (PD): Geometric Mean Ratio of Serum Iron (Fe) Concentrations Relative to Baseline | 2.36 Ratio | Geometric Coefficient of Variation 44 |
Secondary
Pharmacodynamics (PD): Maximum Change in Concentration of Hemoglobin in Reticulocytes (CHr)
Time frame: Baseline through 6 weeks
Population: All participants who received at least one dose of study drug had evaluable CHr values at baseline and post-baseline.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Pharmacodynamics (PD): Maximum Change in Concentration of Hemoglobin in Reticulocytes (CHr) | 1.93 picograms (pg) | Standard Deviation 0.45 |
| 300 mg LY2928057 | Pharmacodynamics (PD): Maximum Change in Concentration of Hemoglobin in Reticulocytes (CHr) | 3.00 picograms (pg) | Standard Deviation 1.18 |
| 600 mg LY2928057 | Pharmacodynamics (PD): Maximum Change in Concentration of Hemoglobin in Reticulocytes (CHr) | 3.60 picograms (pg) | Standard Deviation 2.31 |
| 1000 mg LY2928057 | Pharmacodynamics (PD): Maximum Change in Concentration of Hemoglobin in Reticulocytes (CHr) | 3.20 picograms (pg) | Standard Deviation 1.45 |
Secondary
Pharmacodynamics (PD): Maximum Change in Ferritin
Time frame: Baseline through 6 weeks
Population: All participants who received at least one dose of study drug and had evaluable ferritin values at baseline and post-baseline.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Pharmacodynamics (PD): Maximum Change in Ferritin | 269.21 micrograms/liter (ug/L) | Standard Deviation 112.17 |
| 300 mg LY2928057 | Pharmacodynamics (PD): Maximum Change in Ferritin | 230.28 micrograms/liter (ug/L) | Standard Deviation 80.08 |
| 600 mg LY2928057 | Pharmacodynamics (PD): Maximum Change in Ferritin | 196.46 micrograms/liter (ug/L) | Standard Deviation 90.9 |
| 1000 mg LY2928057 | Pharmacodynamics (PD): Maximum Change in Ferritin | 146.65 micrograms/liter (ug/L) | Standard Deviation 48.05 |
Secondary
Pharmacodynamics (PD): Maximum Change in Hemoglobin
Time frame: Baseline through 6 Weeks
Population: All participants who received at least one dose of study drug had evaluable hemoglobin values at baseline and post-baseline.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Pharmacodynamics (PD): Maximum Change in Hemoglobin | 1.294 millimoles per liter of iron (mml/L-Fe) | Standard Deviation 0.32 |
| 300 mg LY2928057 | Pharmacodynamics (PD): Maximum Change in Hemoglobin | 1.677 millimoles per liter of iron (mml/L-Fe) | Standard Deviation 0.701 |
| 600 mg LY2928057 | Pharmacodynamics (PD): Maximum Change in Hemoglobin | 1.162 millimoles per liter of iron (mml/L-Fe) | Standard Deviation 0.367 |
| 1000 mg LY2928057 | Pharmacodynamics (PD): Maximum Change in Hemoglobin | 1.348 millimoles per liter of iron (mml/L-Fe) | Standard Deviation 0.563 |
Secondary
Pharmacodynamics (PD): Maximum Change in Mean Corpuscular Hemoglobin Concentration (MCHC)
Time frame: Baseline through 6 weeks
Population: All participants who received at least one dose of study drug and had evaluable MCHC values at baseline and post-baseline.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Pharmacodynamics (PD): Maximum Change in Mean Corpuscular Hemoglobin Concentration (MCHC) | 1.4 millimoles/liter of iron (mml/L-Fe) | Standard Deviation 0.5 |
| 300 mg LY2928057 | Pharmacodynamics (PD): Maximum Change in Mean Corpuscular Hemoglobin Concentration (MCHC) | 1.2 millimoles/liter of iron (mml/L-Fe) | Standard Deviation 0.4 |
| 600 mg LY2928057 | Pharmacodynamics (PD): Maximum Change in Mean Corpuscular Hemoglobin Concentration (MCHC) | 1.6 millimoles/liter of iron (mml/L-Fe) | Standard Deviation 0.7 |
| 1000 mg LY2928057 | Pharmacodynamics (PD): Maximum Change in Mean Corpuscular Hemoglobin Concentration (MCHC) | 1.5 millimoles/liter of iron (mml/L-Fe) | Standard Deviation 0.6 |
Secondary
Pharmacodynamics (PD): Maximum Change in Mean Corpuscular Hemoglobin (MCH)
Time frame: Baseline through 6 weeks
Population: All participants who received at least one dose of study drug and had evaluable MCH values at baseline and post-baseline.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Pharmacodynamics (PD): Maximum Change in Mean Corpuscular Hemoglobin (MCH) | 0.107 femtomoles of iron (fmol[Fe]) | Standard Deviation 0.029 |
| 300 mg LY2928057 | Pharmacodynamics (PD): Maximum Change in Mean Corpuscular Hemoglobin (MCH) | 0.105 femtomoles of iron (fmol[Fe]) | Standard Deviation 0.027 |
| 600 mg LY2928057 | Pharmacodynamics (PD): Maximum Change in Mean Corpuscular Hemoglobin (MCH) | 0.091 femtomoles of iron (fmol[Fe]) | Standard Deviation 0.05 |
| 1000 mg LY2928057 | Pharmacodynamics (PD): Maximum Change in Mean Corpuscular Hemoglobin (MCH) | 0.080 femtomoles of iron (fmol[Fe]) | Standard Deviation 0.034 |
Secondary
Pharmacodynamics (PD): Maximum Change in Mean Corpuscular Volume (MCV)
Time frame: Baseline through 6 weeks
Population: All participants who received at least one dose of study drug and had evaluable MCV values at baseline and post-baseline.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Pharmacodynamics (PD): Maximum Change in Mean Corpuscular Volume (MCV) | 5.9 femtoliters (fL) | Standard Deviation 4.6 |
| 300 mg LY2928057 | Pharmacodynamics (PD): Maximum Change in Mean Corpuscular Volume (MCV) | 5.2 femtoliters (fL) | Standard Deviation 1.9 |
| 600 mg LY2928057 | Pharmacodynamics (PD): Maximum Change in Mean Corpuscular Volume (MCV) | 6.2 femtoliters (fL) | Standard Deviation 1.7 |
| 1000 mg LY2928057 | Pharmacodynamics (PD): Maximum Change in Mean Corpuscular Volume (MCV) | 7.0 femtoliters (fL) | Standard Deviation 3.2 |
Secondary
Pharmacodynamics (PD): Maximum Change in Red Blood Cell (RBC) Count
Time frame: Baseline through 6 weeks
Population: All participants who received at least one dose of study drug and had evaluable RBC values at baseline and post-baseline.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Pharmacodynamics (PD): Maximum Change in Red Blood Cell (RBC) Count | 0.686 tera per liter (TI/L) | Standard Deviation 0.135 |
| 300 mg LY2928057 | Pharmacodynamics (PD): Maximum Change in Red Blood Cell (RBC) Count | 0.900 tera per liter (TI/L) | Standard Deviation 0.341 |
| 600 mg LY2928057 | Pharmacodynamics (PD): Maximum Change in Red Blood Cell (RBC) Count | 0.627 tera per liter (TI/L) | Standard Deviation 0.228 |
| 1000 mg LY2928057 | Pharmacodynamics (PD): Maximum Change in Red Blood Cell (RBC) Count | 0.725 tera per liter (TI/L) | Standard Deviation 0.299 |
Secondary
Pharmacodynamics (PD): Maximum Change in Reticulocyte Count
Time frame: Baseline through 6 weeks
Population: All participants who received at least one dose of study drug and had evaluable reticulocyte values at baseline and post-baseline.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Pharmacodynamics (PD): Maximum Change in Reticulocyte Count | 49 gigaparticles per liter (GI/L) | Standard Deviation 37.6 |
| 300 mg LY2928057 | Pharmacodynamics (PD): Maximum Change in Reticulocyte Count | 72.17 gigaparticles per liter (GI/L) | Standard Deviation 29.21 |
| 600 mg LY2928057 | Pharmacodynamics (PD): Maximum Change in Reticulocyte Count | 40.73 gigaparticles per liter (GI/L) | Standard Deviation 13.81 |
| 1000 mg LY2928057 | Pharmacodynamics (PD): Maximum Change in Reticulocyte Count | 74.25 gigaparticles per liter (GI/L) | Standard Deviation 78.73 |
Secondary
Pharmacodynamics (PD): Maximum Change in Transferrin Saturation (TSat)
Time frame: Baseline through 6 weeks
Population: All participants who received at least one dose of study drug and had evaluable TSat values at baseline and post-baseline.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Pharmacodynamics (PD): Maximum Change in Transferrin Saturation (TSat) | 0.2117 percentage change in TSat | Standard Deviation 0.112 |
| 300 mg LY2928057 | Pharmacodynamics (PD): Maximum Change in Transferrin Saturation (TSat) | 0.5250 percentage change in TSat | Standard Deviation 0.0873 |
| 600 mg LY2928057 | Pharmacodynamics (PD): Maximum Change in Transferrin Saturation (TSat) | 0.5000 percentage change in TSat | Standard Deviation 0.155 |
| 1000 mg LY2928057 | Pharmacodynamics (PD): Maximum Change in Transferrin Saturation (TSat) | 0.4375 percentage change in TSat | Standard Deviation 0.0624 |
Secondary
Pharmacokinetics: Area Under the Concentration Curve From Time Zero to Infinity (AUC[0-inf]) of LY2928057
Time frame for Cycle 2: Predose, end of infusion, prior to end of dialysis or 2h, post dialysis or 4h, 2d, 4d, 7d, 9d, 11d postdose; Time frame for Cycle 3: Predose, end of infusion, prior to end of dialysis or 2h, post dialysis or 4h, 2d, 4d, 7d, 9d, 11d, 14d postdose;
Time frame: Cycle 1: Predose, end of infusion, 2hours(h), 4h, 2d, 4d, 7d, 9d, 11d postdose
Population: All participants who received at least one dose of LY2928057 and had evaluable plasma values.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Pharmacokinetics: Area Under the Concentration Curve From Time Zero to Infinity (AUC[0-inf]) of LY2928057 | Cycle 2 (Second dose) | 1640 micrograms x hours/milliliter(µg*h/mL) | Geometric Coefficient of Variation 42 |
| Placebo | Pharmacokinetics: Area Under the Concentration Curve From Time Zero to Infinity (AUC[0-inf]) of LY2928057 | Cycle 1 (First dose) | 1560 micrograms x hours/milliliter(µg*h/mL) | Geometric Coefficient of Variation 39 |
| Placebo | Pharmacokinetics: Area Under the Concentration Curve From Time Zero to Infinity (AUC[0-inf]) of LY2928057 | Cycle 3 (Third dose) | 1520 micrograms x hours/milliliter(µg*h/mL) | Geometric Coefficient of Variation 40 |
| 300 mg LY2928057 | Pharmacokinetics: Area Under the Concentration Curve From Time Zero to Infinity (AUC[0-inf]) of LY2928057 | Cycle 2 (Second dose) | 6970 micrograms x hours/milliliter(µg*h/mL) | Geometric Coefficient of Variation 40 |
| 300 mg LY2928057 | Pharmacokinetics: Area Under the Concentration Curve From Time Zero to Infinity (AUC[0-inf]) of LY2928057 | Cycle 1 (First dose) | 7340 micrograms x hours/milliliter(µg*h/mL) | Geometric Coefficient of Variation 33 |
| 300 mg LY2928057 | Pharmacokinetics: Area Under the Concentration Curve From Time Zero to Infinity (AUC[0-inf]) of LY2928057 | Cycle 3 (Third dose) | 6520 micrograms x hours/milliliter(µg*h/mL) | Geometric Coefficient of Variation 25 |
| 600 mg LY2928057 | Pharmacokinetics: Area Under the Concentration Curve From Time Zero to Infinity (AUC[0-inf]) of LY2928057 | Cycle 1 (First dose) | 11200 micrograms x hours/milliliter(µg*h/mL) | Geometric Coefficient of Variation 24 |
| 600 mg LY2928057 | Pharmacokinetics: Area Under the Concentration Curve From Time Zero to Infinity (AUC[0-inf]) of LY2928057 | Cycle 3 (Third dose) | 12000 micrograms x hours/milliliter(µg*h/mL) | — |
| 600 mg LY2928057 | Pharmacokinetics: Area Under the Concentration Curve From Time Zero to Infinity (AUC[0-inf]) of LY2928057 | Cycle 2 (Second dose) | 16100 micrograms x hours/milliliter(µg*h/mL) | Geometric Coefficient of Variation 31 |
Secondary
Pharmacokinetics: Maximum Concentration (Cmax) of LY2928057
Time frame for Cycle 2: Predose, end of infusion, prior to end of dialysis or 2h, post dialysis or 4h, 2 days (d), 4d, 7d, 9d, 11d postdose; Time frame for Cycle 3: Predose, end of infusion, prior to end of dialysis or 2h, post dialysis or 4h, 2d, 4d, 7d, 9d, 11d, 14d postdose
Time frame: Cycle 1: Predose, end of infusion, 2hours(h), 4h, 2d, 4d, 7d, 9d, 11d postdose;
Population: All participants who received at least one dose of LY2928057 and had evaluable plasma values.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Pharmacokinetics: Maximum Concentration (Cmax) of LY2928057 | Cycle 2 (Second dose) | 70.0 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 21 |
| Placebo | Pharmacokinetics: Maximum Concentration (Cmax) of LY2928057 | Cycle 1 (First dose) | 67.3 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 25 |
| Placebo | Pharmacokinetics: Maximum Concentration (Cmax) of LY2928057 | Cycle 3 (Third dose) | 62.8 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 21 |
| 300 mg LY2928057 | Pharmacokinetics: Maximum Concentration (Cmax) of LY2928057 | Cycle 2 (Second dose) | 213 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 49 |
| 300 mg LY2928057 | Pharmacokinetics: Maximum Concentration (Cmax) of LY2928057 | Cycle 1 (First dose) | 274 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 104 |
| 300 mg LY2928057 | Pharmacokinetics: Maximum Concentration (Cmax) of LY2928057 | Cycle 3 (Third dose) | 177 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 34 |
| 600 mg LY2928057 | Pharmacokinetics: Maximum Concentration (Cmax) of LY2928057 | Cycle 1 (First dose) | 312 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 21 |
| 600 mg LY2928057 | Pharmacokinetics: Maximum Concentration (Cmax) of LY2928057 | Cycle 3 (Third dose) | 358 micrograms per milliliter (µg/mL) | — |
| 600 mg LY2928057 | Pharmacokinetics: Maximum Concentration (Cmax) of LY2928057 | Cycle 2 (Second dose) | 397 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 30 |