Kidney Failure, Chronic, Renal Insufficiency, Chronic
Conditions
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.
Interventions
DRUGLY2409021
Administered orally
Sponsors
Eli Lilly and Company
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY2409021 | Predose, 0.5, 1, 2, 4, 6, 7, 8, 9, 10, 12, 24, 48, 72, 96, 144, 192, 264, 336 hours postdose |
| Pharmacokinetics (PK): Area Under the Concentration Curve From Time Zero to Infinity (AUC 0-∞) of LY2409021 | Predose, 0.5, 1, 2, 4, 6, 7, 8, 9, 10, 12, 24, 48, 72, 96, 144, 192, 264, 336 hours postdose |
Secondary
| Measure | Time frame |
|---|---|
| Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY2409021 in Participants With End Stage Renal Disease (ESRD) Before and After Dialysis | 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 |
| Pharmacokinetics (PK): Area Under the Concentration Curve (AUC) (0-∞) of LY2409021 In Participants With ESRD Before and After Dialysis | 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 |
Countries
Germany, United Kingdom
Participant flow
Pre-assignment details
This study consisted of 5 groups: Group 1-4 (Normal Renal Function Control, Mild, Moderate and Severe Renal Impairment) and Group 5 \[End-stage Renal Disease (ESRD)\].
Participants by arm
| Arm | Count |
|---|---|
| LY2409021 Control Healthy participants received a single 80 mg dose of LY2409021 orally on Day 1 of the study. | 14 |
| LY2409021 Mild Renal Impairment Participants received a single 80 mg dose of LY2409021 orally on Day 1 of the study. | 8 |
| LY2409021 Moderate Renal Impairment Participants received a single 80 mg dose of LY2409021 orally on Day 1 of the study. | 8 |
| LY2409021 Severe Renal Impairment Participants received a single 80 mg dose of LY2409021 orally on Day 1 of the study. | 8 |
| LY2409021 End Stage Renal Disease Participants received a single 80 mg dose of LY2409021 orally on Day 1 of Period 1 of the study and a single 80 mg dose of LY2409021 orally on Day 1 of Period 2 of the study. | 8 |
| Total | 46 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Period 1 (All Groups) | Deviation from protocol | 0 | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | LY2409021 End Stage Renal Disease | LY2409021 Severe Renal Impairment | LY2409021 Moderate Renal Impairment | LY2409021 Mild Renal Impairment | Total | LY2409021 Control |
|---|---|---|---|---|---|---|
| Age, Continuous | 52.0 years STANDARD_DEVIATION 12 | 63.6 years STANDARD_DEVIATION 8.4 | 68.6 years STANDARD_DEVIATION 6.3 | 59.8 years STANDARD_DEVIATION 9.1 | 59.2 years STANDARD_DEVIATION 11.7 | 54.9 years STANDARD_DEVIATION 13 |
| Creatinine clearance (CLcr) | 13.763 mL/min STANDARD_DEVIATION 4.159 | 21.951 mL/min STANDARD_DEVIATION 3.952 | 45.844 mL/min STANDARD_DEVIATION 10.121 | 72.850 mL/min STANDARD_DEVIATION 6.512 | 61.149 mL/min STANDARD_DEVIATION 40.837 | 112.686 mL/min STANDARD_DEVIATION 16.152 |
| Estimated Glomerular Filtration Rate (eGRF) | 8.249 mL/min/1.73m² STANDARD_DEVIATION 1.918 | 17.565 mL/min/1.73m² STANDARD_DEVIATION 7.2 | 40.448 mL/min/1.73m² STANDARD_DEVIATION 12.793 | 68.107 mL/min/1.73m² STANDARD_DEVIATION 15.876 | 51.147 mL/min/1.73m² STANDARD_DEVIATION 35.467 | 91.272 mL/min/1.73m² STANDARD_DEVIATION 17.122 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 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 | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 7 Participants | 8 Participants | 8 Participants | 8 Participants | 45 Participants | 14 Participants |
| Sex: Female, Male Female | 2 Participants | 1 Participants | 3 Participants | 4 Participants | 16 Participants | 6 Participants |
| Sex: Female, Male Male | 6 Participants | 7 Participants | 5 Participants | 4 Participants | 30 Participants | 8 Participants |
| Type 2 Diabetes Mellitus (T2DM) status No | 8 Participants | 8 Participants | 8 Participants | 7 Participants | 45 Participants | 14 Participants |
| Type 2 Diabetes Mellitus (T2DM) status Yes | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 8 / 14 | 4 / 8 | 3 / 8 | 6 / 8 | 5 / 8 |
| serious Total, serious adverse events | 0 / 14 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 |
Outcome results
Primary
Pharmacokinetics (PK): Area Under the Concentration Curve From Time Zero to Infinity (AUC 0-∞) of LY2409021
Time frame: Predose, 0.5, 1, 2, 4, 6, 7, 8, 9, 10, 12, 24, 48, 72, 96, 144, 192, 264, 336 hours postdose
Population: All participants in Groups 1-4 who received at least 1 dose of study drug and had evaluable PK data, excluding one participant (discontinued for a protocol violation). No efficacy or safety data for this participant are included in results.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| LY2409021 Control | Pharmacokinetics (PK): Area Under the Concentration Curve From Time Zero to Infinity (AUC 0-∞) of LY2409021 | 181000 Nanogram x hour per milliliter(ng•h/mL) | Geometric Coefficient of Variation 40 |
| LY2409021 Mild Renal Impairment | Pharmacokinetics (PK): Area Under the Concentration Curve From Time Zero to Infinity (AUC 0-∞) of LY2409021 | 179000 Nanogram x hour per milliliter(ng•h/mL) | Geometric Coefficient of Variation 40 |
| LY2409021 Moderate Renal Impairment | Pharmacokinetics (PK): Area Under the Concentration Curve From Time Zero to Infinity (AUC 0-∞) of LY2409021 | 184000 Nanogram x hour per milliliter(ng•h/mL) | Geometric Coefficient of Variation 56 |
| LY2409021 Severe Renal Impairment | Pharmacokinetics (PK): Area Under the Concentration Curve From Time Zero to Infinity (AUC 0-∞) of LY2409021 | 188000 Nanogram x hour per milliliter(ng•h/mL) | Geometric Coefficient of Variation 24 |
Primary
Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY2409021
Time frame: Predose, 0.5, 1, 2, 4, 6, 7, 8, 9, 10, 12, 24, 48, 72, 96, 144, 192, 264, 336 hours postdose
Population: All participants in Groups 1-4 who received at least 1 dose of study drug and had evaluable PK data, excluding one participant (discontinued for a protocol violation). No efficacy or safety data for this participant are included in results.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| LY2409021 Control | Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY2409021 | 2460 Nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 32 |
| LY2409021 Mild Renal Impairment | Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY2409021 | 2320 Nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 30 |
| LY2409021 Moderate Renal Impairment | Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY2409021 | 2190 Nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 48 |
| LY2409021 Severe Renal Impairment | Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY2409021 | 2080 Nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 25 |
Secondary
Pharmacokinetics (PK): Area Under the Concentration Curve (AUC) (0-∞) of LY2409021 In Participants With ESRD Before and After Dialysis
Time frame: 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
Population: All participants in Group 5 who received at least 1 dose of study drug and had evaluable AUC data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| LY2409021 Control | Pharmacokinetics (PK): Area Under the Concentration Curve (AUC) (0-∞) of LY2409021 In Participants With ESRD Before and After Dialysis | 119000 ng•h/mL | Geometric Coefficient of Variation 51 |
| LY2409021 Mild Renal Impairment | Pharmacokinetics (PK): Area Under the Concentration Curve (AUC) (0-∞) of LY2409021 In Participants With ESRD Before and After Dialysis | 120000 ng•h/mL | Geometric Coefficient of Variation 37 |
Secondary
Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY2409021 in Participants With End Stage Renal Disease (ESRD) Before and After Dialysis
Time frame: 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
Population: All participants in Group 5 who received at least 1 dose of study drug and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| LY2409021 Control | Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY2409021 in Participants With End Stage Renal Disease (ESRD) Before and After Dialysis | 2120 ng/mL | Geometric Coefficient of Variation 72 |
| LY2409021 Mild Renal Impairment | Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY2409021 in Participants With End Stage Renal Disease (ESRD) Before and After Dialysis | 2010 ng/mL | Geometric Coefficient of Variation 37 |