Chronic Kidney Disease
Conditions
Keywords
Renal impairment study, EC5026, sEH inhibitor, Chronic kidney disease (CKD)
Brief summary
The goal of this Phase 1 clinical trial is to assess single dose pharmacokinetics of oral EC5026 in a population with chronic kidney disease. The main questions it aims to answer are: 1. To determine if the PK of a single 8 mg dose of EC5026, administered orally, in adult participants with varying severity of CKD differs from age-matched healthy participants with normal kidney function. 2. To determine if a single 8 mg dose of EC5026, administered orally, in adult participants with varying severity of CKD is safe and well tolerated. Researchers will compare a single 8 mg dose of oral across participants with varying degrees of kidney function impairment (either normal kidney function, or stage 3b chronic kidney disease \[CKD\], or state 4/5 CKD). Participants will be asked to take a single oral dose of EC5026 and will be monitored with PK laboratory assessments and safety assessments (including physical exams, vital signs, electrocardiograms, and others).
Interventions
Oral 8 mg EC5026 tablet
Sponsors
EicOsis Human Health Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
55 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
Each study participant must meet all of the following criteria to be enrolled in this study: 1. Male and female participants must be 55 and older. 2. Study participants must be willing and able to provide written informed consent to participate in the study. 3. Participants with CKD must be stage 3b-5 (estimated glomerular filtration rate (eGFR) ≤ 44 ml/min per 1.73m2) without dialysis. Control participants must have an eGFR of ≥90 ml/min per 1.73m2. 4. Aside from the diagnosis of CKD, study participants must be in overall stable condition, as determined by pre-study medical history, physical examination, clinical laboratory tests, and 12-lead ECG measurements. 5. Study participants must have a body mass index (BMI) of 19-40 kg/m2. Participants with a BMI below 19 kg/m2 may be enrolled at the Investigator's discretion. 6. Study participants must have a systolic blood pressure (BP) of 90-170 mmHg, diastolic BP of 50-90 mmHg, and resting HR of 40-100 beats per min at Screening, with or without stable doses of anti-hypertensive medication. 7. Study participants must be non-smokers or previous smokers who have not smoked within the previous 6 months prior to Screening. 8. Participants taking non-study medications not explicitly listed in the
Exclusion criteria
must be on stable doses of medications for at least 30 days prior to enrollment. Doses should be expected to remain stable for the duration of the study. Standard of care medications for the CKD population which will be allowed at stable doses include, but are not limited to: beta blockers, dihydropyridine calcium channel blockers (i.e. amlodipine), ACE-inhibitors (i.e. lisinopril), ARB (i.e. losartan, valsartan), aspirin, statins, SGLT2 inhibitor (empagliflozin, dapagliflozin), GLP1-RA or GLP-RA/GIP (i.e. semaglutide, tirzepatide), warfarin, direct-acting oral anticoagulants (DOACs - apixaban, rivaroxaban), clopidogrel, and ticagrelor. Study participants taking non-study medications will be included at the opinion of the Investigator and Medical monitor. 9. Male participants must not donate sperm during the study and for 12 months after receiving the last dose of study drug. 10. Male participants must use, from enrollment until at least 2 months after the last dose, a highly effective contraception method (less than 1 pregnancy per 100 people using the method for one year), e.g.: sterilization (e.g., vasectomy), and/or double barrier forms of contraception, including condoms (external or internal) and diaphragm ('cap'). 11. Female participants must be non-pregnant, non-lactating, and either postmenopausal for at least 1 year, or surgically sterile (bilateral tubal ligation ('clipping or tying tubes' or hysterectomy) for at least 3 months, or they must agree to use a highly effective double barrier contraception method (less than 1 pregnancy per 100 people using the method for one year), from 28 days and/or their last confirmed menstrual period prior to study enrollment (whichever is longer) until 2 months after the end of study. Postmenopausal status will be defined as follows: documented postmenopausal status as determined by a physician in medical record at least 1 year prior or amenorrhea duration of 12 consecutive months and a serum FSH value \>40 IU/L (postmenopausal status must be confirmed at Screening). Highly effective double barrier contraception methods include: Intra-uterine device containing either copper or levonorgestrel (e.g., Mirena®), and/or barrier methods of contraception, including condoms (external or internal) and diaphragm ('cap'). Participants/Participant's partner(s) must also use a barrier form of contraception, from the first dose of study drug through until 2 months after the last dose. For all females of childbearing potential, the pregnancy test result must be negative prior to dosing.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area under the plasma concentration-time curve from time 0 to the last measurable concentration (AUC0-t) | 14 days | The area under the plasma concentration-time curve from dosing until the last measurable concentration. Plasma concentrations will be measured from blood samples collected at prespecified time points (0, 2, 4, 6, 8, 24 hours, and 3, 5, 7, 14 days after administration) using a validated bioanalytical assay. AUC0-t will be calculated using noncompartmental pharmacokinetic methods and represents systemic exposure to the study drug over the measured sampling interval. |
| Area under the plasma concentration-time curve from time 0 extrapolated to infinity (AUC0-∞) | 14 days | The area under the plasma concentration-time curve from dosing extrapolated to infinite time. Plasma concentrations will be measured from blood samples collected at prespecified time points (see above) using a validated bioanalytical assay. AUC0-∞ will be calculated using noncompartmental pharmacokinetic methods and represents the total systemic exposure to the study drug. |
| Maximum observed plasma concentration (Cmax) | 14 days | The highest observed plasma concentration of the study drug following administration. Plasma concentrations will be measured from blood samples collected at prespecified time points (see above) using a validated bioanalytical assay. |
| Time to the maximum observed concentration of the drug (Tmax) | 14 days | The time from study drug administration to the maximum observed plasma concentration (Cmax). Tmax will be determined directly from the observed plasma concentration-time data. |
| Apparent terminal elimination rate constant (Kel) | 14 days | The apparent rate at which the study drug is eliminated from plasma during the terminal phase after administration. Kel will be estimated from the terminal log-linear portion of the plasma concentration-time curve using noncompartmental pharmacokinetic methods. |
| Terminal elimination half-life of the drug (t½). | 14 days | The time required for the plasma concentration of the study drug to decrease by 50% during the terminal elimination phase. Half-life will be estimated from the terminal elimination rate constant using noncompartmental pharmacokinetic methods. |
| Apparent clearance (CL/F). | 14 days | The apparent volume of plasma from which the study drug is removed per unit time following oral administration, accounting for unknown oral bioavailability (F). Apparent clearance will be estimated using noncompartmental pharmacokinetic methods. |
| Apparent volume of distribution during the terminal phase (Vz/F) | 14 days | The apparent volume into which the study drug distributes during the terminal elimination phase following oral administration, accounting for unknown oral bioavailability (F). This parameter will be estimated using noncompartmental pharmacokinetic methods. |
| Renal clearance (CLR) | 48 hours | The apparent volume of plasma from which unchanged study drug is removed by the kidneys per unit time. Renal clearance will be calculated using plasma concentration and urine excretion data collected over prespecified sampling intervals. |
| Amount of unchanged drug excreted in urine (Ae). | 48 hours | The cumulative amount of unchanged study drug recovered in urine following study drug administration. Urine samples will be collected over prespecified time intervals and analyzed using a validated bioanalytical assay. |
| Fraction of eliminated dose (Fe%) | 48 hours | The percentage of the administered study drug dose recovered unchanged in urine over the specified collection period. Fe% will be calculated from the cumulative amount of unchanged drug excreted in urine relative to the administered dose. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence, intensity, relationship, and seriousness of treatment-emergent adverse events (TEAEs) | 14 days | Treatment-emergent adverse events are adverse events that begin or worsen after administration of study drug. Adverse events will be assessed throughout the study and summarized by incidence, intensity (severity), relationship to study drug as determined by the investigator, and seriousness. Adverse events will be coded using the current version of the Medical Dictionary for Regulatory Activities (MedDRA). |
| Treatment-emergent changes in vital signs | 14 days | Vital signs, including systolic and diastolic blood pressure, heart rate, respiratory rate, body temperature, and body weight, will be measured at prespecified study visits. Treatment-emergent changes from baseline and clinically significant abnormalities will be summarized. |
| Treatment-emergent changes in hematology laboratory parameters | 14 days | Hematology laboratory assessments, including complete blood count and differential, will be performed at prespecified study visits. Treatment-emergent changes from baseline and clinically significant laboratory abnormalities will be summarized. |
| Treatment-emergent changes in serum chemistry laboratory parameters | 14 days | Serum chemistry laboratory assessments, including electrolytes, liver function tests, glucose, and other serum chemistry analytes, will be performed at prespecified study visits. Treatment-emergent changes from baseline and clinically significant laboratory abnormalities will be summarized. |
| Treatment-emergent changes in renal function assessments | 14 days | Renal function will be assessed using serum creatinine, estimated glomerular filtration rate (eGFR), blood urea nitrogen (BUN), and urinary albumin-to-creatinine ratio (uACR). Treatment-emergent changes from baseline and clinically significant abnormalities will be summarized. |
| Treatment-emergent changes in 12-lead electrocardiograms (ECGs) | 14 days | Standard 12-lead electrocardiograms will be obtained at prespecified study visits. Treatment-emergent changes from baseline and clinically significant ECG abnormalities, including heart rate, rhythm, conduction intervals, and morphology, will be summarized. |
| Treatment-emergent changes in physical examinations findings | 14 days | Physical examinations will be performed at prespecified study visits. Treatment-emergent clinically significant changes from baseline will be summarized. |
Countries
United States
Contacts
CONTACTEicOsis Senior Clinical Scientist
Outcome results
None listed