An Open-Label, Single-Dose Study to Evaluate the Pharmacokinetics of MK-5684 in Male Participants With Severe Renal Impairment and With End-stage Renal Disease
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 24
- 试验地点
- 2
- 主要终点
- Area Under the Concentration Versus Time Curve from 0 to Infinity (AUC0-inf) After a Single Dose of MK-5684
研究概览
简要总结
The goal of the study is to learn what happens to levels of MK-5684 in people with severe renal impairment and end-stage renal disease versus a healthy person's body over time. Researchers will compare what happens to MK-5684 after hemodialysis in people with severe renal impairment and end-stage renal disease versus healthy people.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Inclusion criteria include, but are not limited to:
- •All Participants
- •Is a continuous non-smoker or moderate smoker (≤ 10 cigarettes per day or equivalent) for at least 3 months prior to the first dosing
- •Has a body mass index (BMI) ≥ 18.0 and ≤ 42.0 kg/m^2 at the screening visit
- •Participants with severe renal impairment (RI) (Group 1):
- •Has severely impaired renal function as determined by estimated glomerular filtration rate (eGFR) using the 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation
- •Participants with end-stage renal disease (ESRD) (Group 2):
- •Has ESRD maintained on stable outpatient regimen of intermittent high-flux hemodialysis (HD) (at least 3 times per week) for a minimum of 3 hours per dialysis session, using a complication free well-maintained arteriovenous fistula or arteriovenous graft, for at least 3 months prior to first dosing and is expected and planning to continue HD during the study and at least up to the follow-up visit
- •Healthy Control Participants (Group 3):
- •Has normal renal function
排除标准
- •Exclusion criteria include, but are not limited to:
- •All Participants:
- •Has a history or presence of any of the following: Adrenal insufficiency; Hepatic impairment; Clinically significant hypotension; cardiac arrhythmia; cardiac conduction abnormalities or recurrent unexplained syncopal events; Second- or third-degree atrioventricular (AV) heart block (except in participants with a functional artificial pacemaker); Clinically significant sick sinus syndrome; Any systemic fungal infection; Hypothyroidism; Chronic infection
- •Has a first-degree relative with multiple unexplained syncopal events, unexplained cardiac arrest, or sudden cardiac death, or has a known family history of an inherited arrhythmia syndrome (including Brugada syndrome)
- •Has a history of cancer (malignancy)
- •Is positive for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV)
- •Participants with Severe RI (Group 1):
- •Has a history or presence of renal artery stenosis
- •Has had a renal transplant
- •Has ESRD requiring HD
- •Participants with ESRD (Group 2):
- •Has required frequent emergent HD (≥ 3) within a year prior to the first dosing
- •Has a history or presence of renal artery stenosis.
- •Has had a functioning renal transplant within the past 2 years
研究组 & 干预措施
Group 1: Severe Renal Impairment (RI)
Participants will receive a single oral dose of MK-5684 under fasting conditions (on an empty stomach after a 10-hour overnight fast) on Day 1 and a single dose of Hormone replacement therapy (HRT) (prednisone and fludrocortisone) administered approximately 4.5 hours after MK-5684 dosing under fed conditions (eating a normal meal).
干预措施: MK-5684 (Drug)
Group 1: Severe Renal Impairment (RI)
Participants will receive a single oral dose of MK-5684 under fasting conditions (on an empty stomach after a 10-hour overnight fast) on Day 1 and a single dose of Hormone replacement therapy (HRT) (prednisone and fludrocortisone) administered approximately 4.5 hours after MK-5684 dosing under fed conditions (eating a normal meal).
干预措施: Prednisone (Drug)
Group 1: Severe Renal Impairment (RI)
Participants will receive a single oral dose of MK-5684 under fasting conditions (on an empty stomach after a 10-hour overnight fast) on Day 1 and a single dose of Hormone replacement therapy (HRT) (prednisone and fludrocortisone) administered approximately 4.5 hours after MK-5684 dosing under fed conditions (eating a normal meal).
干预措施: Fludrocortisone acetate (Drug)
Group 2: End-stage renal disease (ESRD)
Participants will receive a single oral dose of MK-5684 under fasting conditions (on an empty stomach after a 10-hour overnight fast) in Period 1 and Period 2. In Period 1, participants will receive a single oral dose of MK-5684 approximately 30 minutes prior to their normally scheduled hemodialysis (HD), followed by HRT under fed conditions (eating a normal meal) 4.5 hours after MK-5684 dosing. In Period 2, participants will receive a single oral dose of MK-5684 immediately followed by completion of their normally scheduled HD, and by HRT under fed conditions (eating a normal meal) 4.5 hours after MK-5684 dosing.
干预措施: MK-5684 (Drug)
Group 2: End-stage renal disease (ESRD)
Participants will receive a single oral dose of MK-5684 under fasting conditions (on an empty stomach after a 10-hour overnight fast) in Period 1 and Period 2. In Period 1, participants will receive a single oral dose of MK-5684 approximately 30 minutes prior to their normally scheduled hemodialysis (HD), followed by HRT under fed conditions (eating a normal meal) 4.5 hours after MK-5684 dosing. In Period 2, participants will receive a single oral dose of MK-5684 immediately followed by completion of their normally scheduled HD, and by HRT under fed conditions (eating a normal meal) 4.5 hours after MK-5684 dosing.
干预措施: Prednisone (Drug)
Group 2: End-stage renal disease (ESRD)
Participants will receive a single oral dose of MK-5684 under fasting conditions (on an empty stomach after a 10-hour overnight fast) in Period 1 and Period 2. In Period 1, participants will receive a single oral dose of MK-5684 approximately 30 minutes prior to their normally scheduled hemodialysis (HD), followed by HRT under fed conditions (eating a normal meal) 4.5 hours after MK-5684 dosing. In Period 2, participants will receive a single oral dose of MK-5684 immediately followed by completion of their normally scheduled HD, and by HRT under fed conditions (eating a normal meal) 4.5 hours after MK-5684 dosing.
干预措施: Fludrocortisone acetate (Drug)
Group 3: Healthy Participants
Participants will receive a single oral dose of MK-5684 under fasting conditions (on an empty stomach after a 10-hour overnight fast) on Day 1 and a single dose of Hormone replacement therapy (HRT) (prednisone and fludrocortisone) administered approximately 4.5 hours after MK-5684 dosing under fed conditions (eating a normal meal).
干预措施: MK-5684 (Drug)
Group 3: Healthy Participants
Participants will receive a single oral dose of MK-5684 under fasting conditions (on an empty stomach after a 10-hour overnight fast) on Day 1 and a single dose of Hormone replacement therapy (HRT) (prednisone and fludrocortisone) administered approximately 4.5 hours after MK-5684 dosing under fed conditions (eating a normal meal).
干预措施: Prednisone (Drug)
Group 3: Healthy Participants
Participants will receive a single oral dose of MK-5684 under fasting conditions (on an empty stomach after a 10-hour overnight fast) on Day 1 and a single dose of Hormone replacement therapy (HRT) (prednisone and fludrocortisone) administered approximately 4.5 hours after MK-5684 dosing under fed conditions (eating a normal meal).
干预措施: Fludrocortisone acetate (Drug)
结局指标
主要结局
Area Under the Concentration Versus Time Curve from 0 to Infinity (AUC0-inf) After a Single Dose of MK-5684
时间窗: At protocol specific time points pre-dose and up to 72 hours post-dose
Blood samples will be collected to determine the AUC0-inf of MK-5684 in plasma.
Area Under the Concentration Versus Time Curve From 0 to the Time of the Last Quantifiable Sample (AUC0-last) of MK-5684
时间窗: At protocol specific time points pre-dose and up to 72 hours post-dose
Blood samples will be collected to determine the AUC0-last of MK-5684 in plasma.
Area Under the Concentration Versus Time Curve From 0 to 24 Hours After Dosing (AUC0-24) of MK-5684
时间窗: At protocol specific time points pre-dose and up to 24 hours post-dose
Blood samples will be collected to determine the AUC0-24 of MK-5684 in plasma.
Maximum Observed Drug Concentration (Cmax) After the Administration of a Given Dose of MK-5684
时间窗: At protocol specific time points pre-dose and up to 72 hours post-dose
Blood samples will be collected to determine the Cmax of MK-5684 in plasma.
Time to Maximum Observed Plasma Drug Concentration (Tmax) of MK-5684
时间窗: At protocol specific time points pre-dose and up to 72 hours post-dose
Blood samples will be collected to determine the Tmax of MK-5684 in plasma.
Apparent Terminal Half-Life (t½) of MK-5684
时间窗: At protocol specific time points pre-dose and up to 72 hours post-dose
Blood samples will be collected to determine the t1/2 of MK-5684 in plasma.
Apparent Clearance (CL/F) of MK-5684
时间窗: At protocol specific time points pre-dose and up to 72 hours post-dose
Blood samples will be collected to determine the CL/F of MK-5684 in plasma.
Apparent Volume of Distribution During Terminal Phase (Vz/F) of MK-5684
时间窗: At protocol specific time points pre-dose and up to 72 hours post-dose
Blood samples will be collected to determine the Vz/F of MK-5684 in plasma.
次要结局
- Number of Participants who Experience an Adverse Event (AE)(Up to ~21 days)
- Number of Participants who Discontinue Study Intervention Due to an AE(Up to ~7 days)
- Dialysis Clearance (CLD) of MK5684 Based on Plasma(At protocol specific time points pre-dose and up to 4.5 hours post-dose)
- Concentration of Dialysate (CD) of MK-5684 Samples(At protocol specific time points pre-dose and up to 4.5 hours post-dose)
- Amount of drug (AD) of MK-5684 recovered from each dialysate collection(At protocol specific time points pre-dose and up to 4.5 hours post-dose)