Clinical trial NCT01929109: A Study of LY2409021 in Participants With Different Levels of Kidney Function
Official title: Pharmacokinetics of LY2409021 Following Administration to Subjects With Varying Degrees of Renal Function
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Kidney Failure, Chronic
Renal Insufficiency, Chronic
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2013-08-27
Enrollment: 47
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: The purpose of this study was to measure how much of the study drug, LY2409021, gets into the blood stream and how long it takes the body to get rid of it when given to participants with different levels of kidney function. There were five study groups. Each participant only enrolled in one group. Participants in groups 1 through 4 were healthy or have mild, moderate, or severe kidney disease. They completed one study period lasting about 29 days. Study group 5 enrolled participants with kidney disease who were on dialysis. They have completed two study periods which together last about 59 days. Screening was required within 21 days prior to the start of the study for all participants.


Eligibility criteria: Inclusion Criteria:

Inclusion Criteria for ALL Participants

* Male participants must agree to use a reliable method of birth control in addition to having their partner use another method for the duration of the study and for 3 months after the last dose of LY2409021
* Female participants must not be of child-bearing potential
* Participants have a body mass index (BMI) of 18 to 40 kilogram per meter square (kg/m\^2), inclusive, at screening

Additional Inclusion Criteria for Control (Healthy) Participants

- Control participants must have normal renal function, assessed by mean estimated creatinine clearance (CLcr) greater than or equal to (≥)90 milliliter per minute (mL/min) at screening and day before dosing

Additional Inclusion Criteria for Participants with Mild-to-Severe Renal Impairment or End Stage Renal Disease (ESRD)

- Males or females with stable mild-to-severe renal impairment, assessed by estimated CLcr, or with ESRD requiring hemodialysis (or hemodiafiltration) for at least 3 months

Additional Inclusion Criteria for Participants with Type 2 Diabetes Mellitus (T2DM)

- Participants with T2DM that are being treated with diet or exercise alone or receive treatment with insulin

Exclusion Criteria:

Exclusion Criteria for ALL Participants

* Participants that require peritoneal dialysis
* Participants that have a current, functioning, organ transplant
* Participants who show evidence of significant active uncontrolled endocrine or autoimmune abnormalities (for example, thyroid disease, pernicious anemia) as judged by the screening physician
* Participants who had a febrile illness within 3 days prior to screening
* Participants with an abnormality in the 12-lead Electrocardiogram (ECG) that, in the opinion of the investigator, increases the risks associated with participating in the study. \[Participants with a QT interval corrected using Fridericia's (QTcF) formula \>450 millisecond (msec) or a PR interval \>0.22 sec on the screening ECG, or who have risk factors for Torsades de Pointes\]
* Participants who show evidence of significant active neuropsychiatric disease
* Participants that are currently using or intend to use potent inhibitors of cytochrome P450 (CYP)3A, which include but are not limited to atazanavir, indinavir, nelfinavir, ritonavir, clarithromycin, itraconazole, ketoconazole, nefazodone, saquinavir, and telithromycin
* Participants who are currently using drugs with a narrow therapeutic index (for example, digoxin,lithium, phenytoin, theophylline, and warfarin)
* Participants that are currently using drugs that are known to prolong the QT interval

Additional Exclusion Criteria for Participants with Mild, Moderate or Severe Renal Impairment or ESRD:

* Participants that have used any drug indicated for medical care of the participant's renal impairment, which is not established in dose and administered for at least 7 days before LY2409021 administration
* Participants with poorly controlled hypertension (systolic blood pressure (BP) less than (\>)160, diastolic BP \>95 mm Hg) and/or evidence of labile blood pressure including symptomatic postural hypotension
* Participants with hemoglobin \<9 grams per deciliter (g/dL) or significant active hematologic disease from causes other than underlying renal disease

Additional Exclusion Criteria for Participants with T2DM:

* Participants who use an oral or injectable antihyperglycemic agent, except for insulin, within 1 month prior to dosing (Day 1)
* Participants who have experienced a ketoacidotic episode (pH \<7.3) requiring hospitalization in the last 6 months

Primary outcomes:
measure: Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY2409021
timeFrame: Predose, 0.5, 1, 2, 4, 6, 7, 8, 9, 10, 12, 24, 48, 72, 96, 144, 192, 264, 336 hours postdose
measure: Pharmacokinetics (PK): Area Under the Concentration Curve From Time Zero to Infinity (AUC 0-∞) of LY2409021
timeFrame: Predose, 0.5, 1, 2, 4, 6, 7, 8, 9, 10, 12, 24, 48, 72, 96, 144, 192, 264, 336 hours postdose
Secondary outcomes:
measure: Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY2409021 in Participants With End Stage Renal Disease (ESRD) Before and After Dialysis
timeFrame: Period 1 (Dialysis) and Period 2 (Non Dialysis) Predose, 0.5, 1, 2, 4, 6, 7, 8, 9, 10, 12, 24, 48, 72, 96, 144, 192, 264, 336 hours postdose
measure: Pharmacokinetics (PK): Area Under the Concentration Curve (AUC) (0-∞) of LY2409021 In Participants With ESRD Before and After Dialysis
timeFrame: Period 1 (Dialysis) and Period 2 (Non Dialysis)- Predose, 0.5, 1, 2, 4, 6, 7, 8, 9, 10, 12, 24, 48, 72, 96, 144, 192, 264, 336 hours postdose
Other outcomes:
Locations:
city: Munich
country: Germany
facility: 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.
city: Liverpool
country: United Kingdom
facility: 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.
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: