A Single-Dose, Dose-Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of LY3113593 in Healthy Subjects and Patients With Chronic Kidney Disease Treated With Hemodialysis
Overview
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Eli Lilly and Company
- Enrollment
- 64
- Locations
- 3
- Primary Endpoint
- Number of Participants With One or More Serious Adverse Event (s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration
Overview
Brief Summary
The purpose of this study is to look at the tolerability and safety of LY3113593. Study doctors will see how safe it is and whether it produces side effects following a single injection into a vein or under the skin in healthy participants (Part A) and participants with chronic kidney disease treated with hemodialysis (Part B). The study will also measure how much of the study drug gets into the blood stream, how long it takes the body to get rid of the study drug and what effects the study drug has on the body.
This is the first time that this study drug is being given to participants. This study is for research purposes only and is not intended to treat any medical condition. For each participant, the study will last about 85 days, not including screening. Screening is required within 28 days prior to the start of the study.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Other
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Healthy Participants:
- •Healthy males or females
- •Participants have a body mass index (BMI) of 18.5 to 29.9 kilogram per meter square (kg/m\^2), inclusive at screening
- •Participants Treated with Hemodialysis:
- •Participants are males or females who have end-stage renal disease (ESRD) and have been receiving adequate maintenance hemodialysis (3 times weekly) for at least 12 weeks prior to screening
- •Participants have a hemoglobin value greater than or equal to (≥)9.0 grams per deciliter (g/dL) and less than or equal to (≤)12.5 g/dL at screening
- •Participants have a body mass index (BMI) of 18.5 to 45.0 kg/m\^2, inclusive, at screening
- •Both Populations:
- •Male participants agree to use a reliable method of birth control and avoid donating sperm during the study and for 3 months following the dose of the investigational product
- •Female participants must not be of child-bearing potential
Exclusion Criteria
- •Healthy Participants:
- •Participants that have a history or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; of constituting a risk when taking the study medication; or of interfering with the interpretation of data
- •Participants that have used or intend to use over-the-counter or prescription medication, including herbal medications within 14 days prior to dosing
- •Participants Treated with Hemodialysis:
- •Participants that have a history of myocardial infarction, acute coronary syndrome, stroke or transient ischemic attacks within the prior 6 months
- •Participants that have heart failure that results in dyspnea at rest or during minimal exercise
- •Participants that have poorly controlled hypertension
- •Participants that have a history of significant thrombotic disease, pulmonary hypertension, significant hematological disease or current liver disease, known hepatic or biliary abnormalities
- •Participants that had a blood transfusion within the prior 12 weeks or an anticipated need for blood transfusion during the study
- •Participants that have evidence of active peptic, duodenal, or esophageal ulcer disease or gastrointestinal bleeding within the prior 12 weeks
Arms & Interventions
Placebo IV (Part B)
Single dose of placebo matching LY3113593 administered IV
Intervention: Placebo (Drug)
LY3113593 IV (Part B)
Single dose of LY3113593 administered IV
Intervention: LY3113593 (Drug)
LY3113593 IV (Part A)
Single dose of LY3113593 administered intravenous (IV) at a minimum of six dose levels
Intervention: LY3113593 (Drug)
Placebo IV (Part A)
Single dose of placebo matching LY3113593 administered IV
Intervention: Placebo (Drug)
LY3113593 SC (Part A)
Single dose of LY3113593 administered subcutaneous (SC)
Intervention: LY3113593 (Drug)
Placebo SC (Part A)
Single dose of placebo matching LY3113593 administered SC
Intervention: Placebo (Drug)
Outcomes
Primary Outcomes
Number of Participants With One or More Serious Adverse Event (s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration
Time Frame: Baseline through end of study (Day 85)
The number of participants with 1 or more SAEs assessed as related to the study drug and is summarized cumulatively. A serious adverse event is defined as an event that results in death, initial or prolonged hospitalization, is life-threatening, leads to persistent or significant disability/incapacity, is associated with congenital anomaly/birth defect, or is considered significant by the investigator for any other reason. A summary of all SAE's, regardless of causality, is located in the Reported Adverse Events section.
Secondary Outcomes
- Pharmacokinetics: Maximum Concentration (Cmax) of LY3113593(Day 1: pre-dose, 30 minutes, 2 hours, 4 hours, 12 hours; Days 2, 3, 5, 8, 15, 22, 29, 43, 57, 71, and 85)
- Pharmacokinetics: Area Under the Concentration Curve to Infinity (AUC (0-∞)) of LY3113593(Day 1: pre-dose, 30 minutes, 2 hours, 4 hours, 12 hours; Days 2, 3, 5, 8, 15, 22, 29, 43, 57, 71, and 85)
- Pharmacokinetics: Absolute Bioavailability of LY3113593 SC Versus IV Based on AUC Ratios(Day 1: pre-dose, 30 minutes, 2 hours, 4 hours, 12 hours; Days 2, 3, 5, 8, 15, 22, 29, 43, 57, 71, and 85)
- Pharmacodynamics: Maximum Change From Baseline in Iron Parameter Profile of LY3113593(Baseline, Day 85)
- Pharmacodynamics: Maximum Absolute Change From Baseline in TSat Parameter Profile of LY3113593(Baseline, Day 85)
- Pharmacodynamics: Maximum Change From Baseline in Hemoglobin (Hb) Parameter Profile of LY3113593(Baseline, Day 85)