A Multiple-Dose, Dose-Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of LY2928057 in Hemodialysis Patients
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 28
- 试验地点
- 4
- 主要终点
- Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •Any cause of anemia other than renal disease
- •A history of hyporesponsiveness to ESA
研究组 & 干预措施
Placebo (Reduced ESA)
Multiple doses of placebo administered IV either Q2W or QW for 6 weeks. Participants reduced their personal physician-prescribed ESA dose before treatment.
干预措施: Placebo (Drug)
LY2928057 (No ESA)
Multiple doses of LY2928057 administered intravenously (IV) either once every 2 weeks (Q2W) or once per week (QW) for 6 weeks. Participants discontinued their personal physician-prescribed erythropoiesis stimulating agent (ESA) before treatment.
干预措施: LY2928057 (Drug)
LY2928057 (Reduced ESA)
Multiple doses of LY2928057 administered IV either Q2W or QW for 6 weeks. Participants reduced their personal physician-prescribed ESA dose before treatment.
干预措施: LY2928057 (Drug)
Placebo (No ESA)
Multiple doses of placebo administered IV either Q2W or QW for 6 weeks. Participants discontinued their personal physician-prescribed ESA dose before treatment.
干预措施: Placebo (Drug)
结局指标
主要结局
Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration
时间窗: 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
时间窗: Baseline, Day 42
次要结局
- Pharmacodynamics (PD): Maximum Change in Hemoglobin(Baseline through 6 Weeks)
- 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): Geometric Mean Ratio of Serum Iron (Fe) Concentrations Relative to Baseline(Baseline, 6 weeks)
- Pharmacodynamics (PD): Maximum Change in Mean Corpuscular Hemoglobin (MCH)(Baseline through 6 weeks)
- Pharmacodynamics (PD): Maximum Change in Ferritin(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 Concentration (MCHC)(Baseline through 6 weeks)
- 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)
- Pharmacokinetics: Maximum Concentration (Cmax) of LY2928057(Cycle 1: Predose, end of infusion, 2hours(h), 4h, 2d, 4d, 7d, 9d, 11d 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)
- Number of Participants With Anti-LY2928057 Antibodies(Baseline through 84 days)