Clinical trial NCT02144285: A Study of LY3113593 in Healthy Participants and Participants With Chronic Kidney Disease Treated With Hemodialysis
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Kidney Failure, Chronic
Keywords: Renal dialysis
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2014-05-21
Enrollment: 64
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.


Eligibility criteria: 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
* Both Populations:

  * Participants that have known allergies to related compounds or any components of the study drug or its formulation, clinically significant multiple or severe drug allergies, or intolerance to topical corticosteroids, or severe post treatment hypersensitivity reactions or history of significant atopy
  * Participants that have participated, within the last 30 days (or 5 half-lives if long half life) in a clinical trial involving an investigational product
  * Participants that have known or ongoing psychiatric disorders

Primary outcomes:
measure: Number of Participants With One or More Serious Adverse Event (s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration
timeFrame: Baseline through end of study (Day 85)
Secondary outcomes:
measure: Pharmacokinetics: Maximum Concentration (Cmax) of LY3113593
timeFrame: 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
measure: Pharmacokinetics: Area Under the Concentration Curve to Infinity (AUC (0-∞)) of LY3113593
timeFrame: 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
measure: Pharmacokinetics: Absolute Bioavailability of LY3113593 SC Versus IV Based on AUC Ratios
timeFrame: 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
measure: Pharmacodynamics: Maximum Change From Baseline in Iron Parameter Profile of LY3113593
timeFrame: Baseline, Day 85
measure: Pharmacodynamics: Maximum Absolute Change From Baseline in TSat Parameter Profile of LY3113593
timeFrame: Baseline, Day 85
measure: Pharmacodynamics: Maximum Change From Baseline in Hemoglobin (Hb) Parameter Profile of LY3113593
timeFrame: Baseline, Day 85
Other outcomes:
Locations:
city: Glendale
country: United States
facility: Parexel Early Phase Unit at Glendale
state: California
city: Orlando
country: United States
facility: Orlando Clinical Research Center
state: Florida
city: Minneapolis
country: United States
facility: Davita Clinical Research
state: Minnesota
Study officials:
affiliation: Eli Lilly and Company
name: 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)
role: STUDY_DIRECTOR
References:
citation: Sheetz M, Barrington P, Callies S, Berg PH, McColm J, Marbury T, Decker B, Dyas GL, Truhlar SME, Benschop R, Leung D, Berg J, Witcher DR. Targeting the hepcidin-ferroportin pathway in anaemia of chronic kidney disease. Br J Clin Pharmacol. 2019 May;85(5):935-948. doi: 10.1111/bcp.13877. Epub 2019 Mar 4.