Renal Impairments
Conditions
Brief summary
The purpose of this Phase 1 study is to understand and compare the amount of EDG-7500 in the blood after a single dose in participants with different levels of kidney function impairment versus participants with normal kidney function. The safety of EDG-7500 in participants with different levels of kidney function impairment will also be evaluated in this study.
Interventions
DRUGEDG-7500
Single dose of EDG-7500
Sponsors
Edgewise Therapeutics, Inc.
Study design
Allocation
NA
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
Key Inclusion Criteria: All Participants * Adult, male or female, 18-75 years of age, inclusive * Female and male participants must follow protocol-specified contraception guidance * Continuous non-smoker or light smoker (≤ 5 cigarettes per day or equivalent) for at least 3 months prior to dosing * BMI ≥ 18.0 and ≤ 40.0 kg/m2 at the screening visit. Participants with Severe, Moderate and Mild Renal Impairment (RI) * With the exception of RI and other stable diseases, participant is sufficiently healthy for study participation including the following: * Heart rate ≥ 40 bpm and ≤ 110 bpm. * QTcF interval ≤ 500 msec and has ECG findings considered normal or not clinically significant. * Liver function test including ALT ≤ ULN, AST ≤ ULN, and total bilirubin ≤ 1.5 ULN * Has impaired renal function as determined by eGFR: * eGFR \<30 mL/min, not requiring hemodialysis, for participants with severe RI. * eGFR ≥30 but \<60 mL/min for participants with moderate RI. * eGFR ≥60 but \<90 mL/min for participants with mild RI. * Has stable renal function with no clinically significant change in renal status at least 28 days prior to dosing and is not currently or has not been previously on dialysis for at least 1 year. Participants with Normal Renal Function * Medically healthy, including the following: * Blood pressure ≥ 90/40 mmHg and ≤ 150/95 mmHg * Heart rate ≥ 40 bpm and ≤ 100 bpm * QTcF interval ≤ 470 msec and has ECG findings considered normal or not clinically significant * Liver function test including ALT ≤ ULN, AST ≤ ULN, and total bilirubin ≤1.5x ULN * Normal renal function with eGFR ≥ 90 mL/min
Exclusion criteria
All Participants * History or presence of alcohol or drug abuse within the past 2 years prior to dosing. * Female participant with a positive pregnancy test at the screening visit or at check-in or who is lactating. * Positive urine or breath alcohol results. Unable to refrain from or anticipates the use of any drugs. * Positive results for HIV, HBsAg, or HCV. * Donation of blood or significant blood loss within 56 days prior to the first dosing. * Plasma donation within 7 days prior to the first dosing. * Participation in another clinical study within 30 days or within 5 half-lives (if known), prior to dosing. Participants with Severe, Moderate, and Mild RI (Cohorts 1, 2, and 4) * History or presence of renal artery stenosis. * Renal transplant or nephrectomy in ≤ 5 years. * Diabetes confirmed with HbA1c \> 8.5%. Participants with Normal Renal Function (Cohort 3) -History of any illness that might confound the results of the study or poses an additional risk to the participant by their participation in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area under the curve from time zero to last quantifiable concentration (AUC0-last) | Pre-dose to day 11 | Area under the plasma concentration time-curve from zero to the last measured concentration (AUC0-last) |
| Area under the curve from time zero to extrapolated infinite time (AUC0-inf) | Pre-dose to day 11 | Area under the plasma concentration time-curve from zero to extrapolated infinite time (AUC0-inf) |
| Maximum observed plasma concentration (Cmax) | Pre-dose to day 11 | — |
| Observed plasma concentration at the end of the dosing interval (C24) | Pre-dose to day 11 | — |
| Time to reach maximum observed plasma concentration (Tmax) | Pre-dose to day 11 | — |
| Plasma elimination half-life (T1/2) | Pre-dose to day 11 | The time measured for the plasma concentration to decrease by one half. |
Secondary
| Measure | Time frame |
|---|---|
| Amount of unchanged drug excreted in urine from zero to 24 hours post dose (Ae0-24) | From day -1 to day 11 |
| Fraction of drug excreted unchanged in urine (fe) | From day -1 to day 11 |
| Renal clearance | From day -1 to day 11 |
Countries
United States
Outcome results
None listed