Renal Impairment Study for Oral EC5026

Assessment of Single Dose Pharmacokinetics of Oral EC5026 in a Population With Chronic Kidney Disease

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).

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.

Exclusion Criteria:

Study participants meeting any of the following criteria will be excluded from the study:

1. Participants who have donated and/or received any blood or blood products (more than 450 mL) within 3 months prior to enrollment.
2. Participants who have used any other investigational drug within 1 month prior to Screening. If the investigational drug is known to have a long half-life, a longer washout period will be done.
3. Participants using opioid medications on a regular basis or pro re nata (PRN). Non-opioid pain medications will be allowed if at a fixed stable dose for more than 1 month prior to Screening with no anticipation of the dose changing during the study. Allowed non-opioid medications include gabapentin, pregabalin, duloxetine, acetaminophen, ibuprofen, celecoxib, meloxicam, other antidepressants including amitriptyline, and other antiepileptics, as well as topical capsaicin and topical lidocaine.
4. Participants who have used (within 30 days of enrollment) or plan on using during the duration of the study any prescription or over-the-counter drugs that are cytochrome P450 3A4 (CYP3A4) inducers or inhibitors (e.g., verapamil, diltiazem, carbamazepine, oxcarbazepine, phenobarbital, phenytoin, cimetidine, paroxetine, fluoxetine, haloperidol, ketoconazole, itraconazole, fluconazole, erythromycin, or clarithromycin).
5. Participants who have used (within 30 days of enrollment) or plan on using during the duration of the study any dietary aids, supplements, or foods that are known to modulate drug metabolizing enzymes (e.g., St. John's wort, grapefruit juice).
6. Participants with difficulty in swallowing oral medications.
7. Participants who have active cancer or have a high risk of cancer recurrence requiring active surveillance. Participants with a personal history of cancer or metastatic cancer in first degree relatives suggestive of elevated cancer risk in the opinion of the investigator.
8. Participants with a history of disorders of the hypothalamic-pituitary-adrenal or hypothalamic-pituitary-gonadal axis
9. Participants with a presence or history of active gastrointestinal disorder, including esophageal or gastroduodenal ulceration, or hepatic, or coagulant disorder within 1 month prior to enrollment
10. Participants with any clinically unstable cardiovascular (including acute coronary syndrome within the 6 months prior to Screening), respiratory, hematological, endocrine disorder, as determined by the study physician.
11. Participants with severe systolic heart failure (Ejection Fraction <35%).
12. Participants with exercise-limiting cardiopulmonary disease including severe valvular heart disease, exertional angina, and/or major atherosclerotic cardiovascular event within last 6 months.
13. Participants with a history of unstable arrhythmia.
14. Participants with clinically significant and persistent electrolyte abnormalities including hypokalemia (K<3.4mEq/dL) or hyperkalemia (K>5.4mEq/dL).
15. Participants with serious psychosocial comorbidities as determined by the Investigator.
16. Participants with current cognitive or major psychiatric disorders, or any other condition that could interfere with compliance with study procedures.
17. Participants with a history of bacterial, fungal, or viral infection requiring treatment with antibiotics, antifungal agents, or antivirals within 1 month prior to enrollment.
18. Participants with confirmed COVID-19, or suspected COVID-19 (e.g., developed symptoms of a respiratory infection such as cough, sore throat, shortness of breath, or fever, but did not get tested for COVID-19) at the time of screening.
19. Participants with confirmed moderate-severe COVID-19 within 2 months of enrollment or with confirmed asymptomatic or mild COVID-19 within 4 weeks of enrollment.
20. Participants who have received a COVID-19 vaccine within 4 weeks of enrollment or are planning on receiving it during the study duration.
21. Participants with medical history of active Hepatitis A, Hepatitis B, Hepatitis C, and/or HIV.
22. Participants with a positive drug or alcohol test during Screening and/or admission (a positive THC test will be allowed as long as it consists of minimal social use, per discretion of Investigator).