Assessment of Single Dose Pharmacokinetics of Oral EC5026 in a Population With Chronic Kidney Disease
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Area under the plasma concentration-time curve from time 0 to the last measurable concentration (AUC0-t)
研究概览
简要总结
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:
- 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.
- 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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 55 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Each study participant must meet all of the following criteria to be enrolled in this study:
- •Male and female participants must be 55 and older.
- •Study participants must be willing and able to provide written informed consent to participate in the study.
- •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 1.73m
- •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.
- •Study participants must have a body mass index (BMI) of 19-40 kg/m
- •Participants with a BMI below 19 kg/m2 may be enrolled at the Investigator's discretion.
- •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.
- •Study participants must be non-smokers or previous smokers who have not smoked within the previous 6 months prior to Screening.
- •Participants taking non-study medications not explicitly listed in the
排除标准
- •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.
- •Male participants must not donate sperm during the study and for 12 months after receiving the last dose of study drug.
- •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').
- •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:
- •Participants who have donated and/or received any blood or blood products (more than 450 mL) within 3 months prior to enrollment.
- •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.
- •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.
- •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).
- •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).
- •Participants with difficulty in swallowing oral medications.
- •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.
- •Participants with a history of disorders of the hypothalamic-pituitary-adrenal or hypothalamic-pituitary-gonadal axis
- •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
- •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.
- •Participants with severe systolic heart failure (Ejection Fraction <35%).
- •Participants with exercise-limiting cardiopulmonary disease including severe valvular heart disease, exertional angina, and/or major atherosclerotic cardiovascular event within last 6 months.
- •Participants with a history of unstable arrhythmia.
- •Participants with clinically significant and persistent electrolyte abnormalities including hypokalemia (K<3.4mEq/dL) or hyperkalemia (K>5.4mEq/dL).
- •Participants with serious psychosocial comorbidities as determined by the Investigator.
- •Participants with current cognitive or major psychiatric disorders, or any other condition that could interfere with compliance with study procedures.
- •Participants with a history of bacterial, fungal, or viral infection requiring treatment with antibiotics, antifungal agents, or antivirals within 1 month prior to enrollment.
- •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.
- •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.
- •Participants who have received a COVID-19 vaccine within 4 weeks of enrollment or are planning on receiving it during the study duration.
- •Participants with medical history of active Hepatitis A, Hepatitis B, Hepatitis C, and/or HIV.
- •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).
结局指标
主要结局
Area under the plasma concentration-time curve from time 0 to the last measurable concentration (AUC0-t)
时间窗: 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-∞)
时间窗: 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)
时间窗: 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)
时间窗: 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)
时间窗: 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).
时间窗: 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).
时间窗: 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)
时间窗: 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)
时间窗: 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).
时间窗: 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%)
时间窗: 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.
次要结局
- Incidence, intensity, relationship, and seriousness of treatment-emergent adverse events (TEAEs)(14 days)
- Treatment-emergent changes in vital signs(14 days)
- Treatment-emergent changes in hematology laboratory parameters(14 days)
- Treatment-emergent changes in serum chemistry laboratory parameters(14 days)
- Treatment-emergent changes in renal function assessments(14 days)
- Treatment-emergent changes in 12-lead electrocardiograms (ECGs)(14 days)
- Treatment-emergent changes in physical examinations findings(14 days)