Study of Pharmacokinetics of a Single IV Dose of CB-238,618 in Subjects With Varying Degrees of Renal Impairment Compared to Healthy Subjects (MK-6183-001)
2019年2月13日 更新者：Cubist Pharmaceuticals LLC
A Phase 1, Non-randomized, Parallel-group, Open-label Study to Characterize the Pharmacokinetics of a Single Intravenous Dose of CB-238,618 in Subjects With Varying Degrees of Renal Impairment Compared to Healthy Subjects
The purpose of this study is to characterize the effect of renal function on the plasma, urine, and dialysate pharmacokinetic profile of MK-6183 (CB-238,618) in humans.
The study will also assess the safety profile and tolerability of MK-6183 in healthy participants, participants with varying degrees of renal impairment (RI), or participants with end-stage renal disease (ESRD) requiring hemodialysis (HD), based on estimated glomerular filtration rate (eGFR).
研究概览
研究类型
介入性
注册 (实际的)
40
阶段
- 阶段1
参与标准
研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。
资格标准
适合学习的年龄
18年 及以上 (成人、年长者)
接受健康志愿者
是的
有资格学习的性别
全部
描述
Inclusion Criteria:
- Participants who are healthy; or who have mild, moderate, or severe RI; or who have ESRD requiring HD. Participants with ESRD requiring HD should have been receiving HD 3 times per week for at least 3 months preceding the initial dose in this study
Exclusion Criteria:
- For healthy participants (Group A): history or presence of any clinically significant illness (e.g., cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, oncologic, musculoskeletal, or psychiatric) or any other condition, including clinically significant anemia, which in the opinion of the investigator would jeopardize the safety of the participant or the validity of the study results
- For participants with RI (Groups B to E): as above, except that RI and other medical conditions commonly associated with renal impairment (eg, hypertension, diabetes, which should be stable for at least three months preceding the initial dose of study medication in this study) are allowed
- Clinically significant abnormalities on physical examination, medical history, 12-lead electrocardiogram (ECG), vital signs, or laboratory values, as judged by the investigator or designee. Subjects with renal impairment should have clinical laboratory values consistent with their disease and approved by the investigator
- Evidence of clinically significant hepatic impairment including alanine aminotransferase or aspartate aminotransferase >1.5 × upper limit of normal (ULN) or bilirubin >1 × ULN
- Hemoglobin <8 g/dL, unless considered stable and not clinically significant in the opinion of the investigator in subjects with ESRD and on HD
- Participants with renal impairment who are not on a chronic stable drug regimen, defined as starting a new drug or changing dosage within 14 days prior to administration of study medication, except for drugs administered in relationship to HD
- Participants with fluctuating or rapidly deteriorating renal function (assessment of the stability of the subject's renal function will be determined by the investigator)
- Participant has a currently functioning renal transplant and/or has been on significant immunosuppressant therapy, as determined by the investigator, within the last 6 months
学习计划
本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。
研究是如何设计的？
设计细节
- 主要用途：治疗
- 分配：非随机化
- 介入模型：并行分配
- 屏蔽：无（打开标签）
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
|
实验性的：Group A: Healthy
Healthy participants with normal renal function (Stage 1: eGFR ≥90 mL/min/1.73m^2).
|
MK-6183 (CB-238,614) is supplied as lyophilized powder 500 mg vial and mixed into solution for 100 mL intravenous (IV) administration over 1 hour.
其他名称：
|
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实验性的：Group B: Mild RI
Participants with mild RI (Stage 2: eGFR ≥60 to <90 mL/min/1.73m^2).
|
MK-6183 (CB-238,614) is supplied as lyophilized powder 500 mg vial and mixed into solution for 100 mL intravenous (IV) administration over 1 hour.
其他名称：
|
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实验性的：Group C: Moderate RI
Participants with moderate RI (Stage 3: eGFR ≥30 to <60 mL/min/1.73m^2).
|
MK-6183 (CB-238,614) is supplied as lyophilized powder 500 mg vial and mixed into solution for 100 mL intravenous (IV) administration over 1 hour.
其他名称：
|
|
实验性的：Group D: Severe RI
Participants with severe RI (Stage 4: eGFR <30 mL/min/1.73m^2)
not receiving HD.
|
MK-6183 (CB-238,614) is supplied as lyophilized powder 500 mg vial and mixed into solution for 100 mL intravenous (IV) administration over 1 hour.
其他名称：
|
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实验性的：Group E: ESRD-HD
Participants with ESRD who are receiving HD for at least 3 months preceding the initial dose in this study (Stage 5).
|
MK-6183 (CB-238,614) is supplied as lyophilized powder 500 mg vial and mixed into solution for 100 mL intravenous (IV) administration over 1 hour.
其他名称：
|
研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Area Under the Plasma Concentration-time Curve (AUC) From Dosing to Last Measurable Concentration (AUC0-last) of MK-6183
大体时间：Groups A to D & Group E: Period 2: Pre-dose and 0.5, 1 (end of infusion; EOI), 1.5, 2, 3, 6, 12, 24, 48, and 72 hours post-dose
|
AUC0-last is the area under the plasma concentration-time curve from the time of dosing to the last post-dose measurable concentration.
Blood samples for Group E were collected both prior to and during HD (Period 1) and after HD (Period 2) [data from Periods 1 and 2 were analyzed separately].
In Period 1, HD commenced 3.5 hours post-dose (HD duration was 3.5 to 4 hours) and sample collection continued until 48 hours post-dose.
The specific time frame of plasma sample collection for Group E: Period 1 was pre-dose, 0.5 hours post-dose, EOI, 1.5 hours post-dose, 2 hours post-dose, 3 hours post-dose (pre-HD), 3.5 hours post-dose with HD, 5 hours post-dose with HD, pre-end of HD, 30 min post-HD, 1 hour post-HD, 2 hours post-HD, 12 hours post-dose, 24 hours post-dose, and 48 hours post-dose.
|
Groups A to D & Group E: Period 2: Pre-dose and 0.5, 1 (end of infusion; EOI), 1.5, 2, 3, 6, 12, 24, 48, and 72 hours post-dose
|
|
AUC From Dosing to ∞ (AUC0-∞) of MK-6183
大体时间：Groups A to D & Group E: Period 2: Pre-dose and 0.5, EOI, 1.5, 2, 3, 6, 12, 24, 48, and 72 hours post-dose
|
AUC0-∞ is the extrapolated area under the plasma concentration-time curve from the time of dosing to infinity.
Blood samples for Group E were collected both prior to and during HD (Period 1) and after HD (Period 2) [data from Periods 1 and 2 were analyzed separately].
In Period 1, HD commenced 3.5 hours post-dose (HD duration was 3.5 to 4 hours) and sample collection continued until 48 hours post-dose.
The specific time frame of plasma sample collection for Group E: Period 1 was pre-dose, 0.5 hours post-dose, EOI, 1.5 hours post-dose, 2 hours post-dose, 3 hours post-dose (pre-HD), 3.5 hours post-dose with HD, 5 hours post-dose with HD, pre-end of HD, 30 min post-HD, 1 hour post-HD, 2 hours post-HD, 12 hours post-dose, 24 hours post-dose, and 48 hours post-dose.
For statistical analyses, Group A is the reference and least squares (LS) mean ratios for tests (Groups B to E) are calculated as test/reference; Group E: Period 1 and Group E: Period 2 were also compared.
|
Groups A to D & Group E: Period 2: Pre-dose and 0.5, EOI, 1.5, 2, 3, 6, 12, 24, 48, and 72 hours post-dose
|
|
Maximum Plasma Drug Concentration (Cmax) of MK-6183
大体时间：Groups A to D & Group E: Period 2: Pre-dose and 0.5, EOI, 1.5, 2, 3, 6, 12, 24, 48, and 72 hours post-dose
|
Cmax is the maximum observed post-dose drug concentration in plasma.
Blood samples for Group E were collected both prior to and during HD (Period 1) and after HD (Period 2) [data from Periods 1 and 2 were analyzed separately].
In Period 1, HD commenced 3.5 hours post-dose (HD duration was 3.5 to 4 hours) and sample collection continued until 48 hours post-dose.
The specific time frame of sample collection for Group E: Period 1 was pre-dose, 0.5 hours post-dose, EOI, 1.5 hours post-dose, 2 hours post-dose, 3 hours post-dose (pre-HD), 3.5 hours post-dose with HD, 5 hours post-dose with HD, pre-end of HD, 30 min post-HD, 1 hour post-HD, 2 hours post-HD, 12 hours post-dose, 24 hours post-dose, and 48 hours post-dose.
For statistical analyses, Group A is the reference and LS mean ratios for tests (Groups B to E) are calculated as test/reference; Group E: Period 1 and Group E: Period 2 were also compared.
|
Groups A to D & Group E: Period 2: Pre-dose and 0.5, EOI, 1.5, 2, 3, 6, 12, 24, 48, and 72 hours post-dose
|
|
Apparent Total Body Clearance of MK-6183 From Plasma (CL)
大体时间：Groups A to D & Group E: Period 2: Pre-dose and 0.5, EOI, 1.5, 2, 3, 6, 12, 24, 48, and 72 hours post-dose
|
CL is a measure of the clearance of drug from plasma via metabolism and excretion.
Blood samples for Group E were collected both prior to and during HD (Period 1) and after HD (Period 2) [data from Periods 1 and 2 were analyzed separately].
In Period 1, HD commenced 3.5 hours post-dose (HD duration was 3.5 to 4 hours) and sample collection continued until 48 hours post-dose.
The specific time frame of plasma sample collection for Group E: Period 1 was pre-dose, 0.5 hours post-dose, EOI, 1.5 hours post-dose, 2 hours post-dose, 3 hours post-dose (pre-HD), 3.5 hours post-dose with HD, 5 hours post-dose with HD, pre-end of HD, 30 min post-HD, 1 hour post-HD, 2 hours post-HD, 12 hours post-dose, 24 hours post-dose, and 48 hours post-dose.
|
Groups A to D & Group E: Period 2: Pre-dose and 0.5, EOI, 1.5, 2, 3, 6, 12, 24, 48, and 72 hours post-dose
|
|
Volume of Distribution at Steady State (Vss) of MK-6183
大体时间：Groups A to D & Group E: Period 2: Pre-dose and 0.5, EOI, 1.5, 2, 3, 6, 12, 24, 48, and 72 hours post-dose
|
Vss is the apparent volume of distribution at steady state for MK-6183.
Blood samples for Group E were collected both prior to and during HD (Period 1) and after HD (Period 2) [data from Periods 1 and 2 were analyzed separately].
In Period 1, HD commenced 3.5 hours post-dose (HD duration was 3.5 to 4 hours) and sample collection continued until 48 hours post-dose.
The specific time frame of sample collection for Group E: Period 1 was pre-dose, 0.5 hours post-dose, EOI, 1.5 hours post-dose, 2 hours post-dose, 3 hours post-dose (pre-HD), 3.5 hours post-dose with HD, 5 hours post-dose with HD, pre-end of HD, 30 min post-HD, 1 hour post-HD, 2 hours post-HD, 12 hours post-dose, 24 hours post-dose, and 48 hours post-dose.
|
Groups A to D & Group E: Period 2: Pre-dose and 0.5, EOI, 1.5, 2, 3, 6, 12, 24, 48, and 72 hours post-dose
|
|
Apparent Plasma Half-life (t½) of MK-6183
大体时间：Groups A to D & Group E: Period 2: Pre-dose and 0.5, EOI, 1.5, 2, 3, 6, 12, 24, 48, and 72 hours post-dose
|
t½ is the amount of time required for the plasma concentration of MK-6183 to reduce by 50%.
Blood samples for Group E were collected both prior to and during HD (Period 1) and after HD (Period 2) [data from Periods 1 and 2 were analyzed separately].
In Period 1, HD commenced 3.5 hours post-dose (HD duration was 3.5 to 4 hours) and sample collection continued until 48 hours post-dose.
The specific time frame of sample collection for Group E: Period 1 was pre-dose, 0.5 hours post-dose, EOI, 1.5 hours post-dose, 2 hours post-dose, 3 hours post-dose (pre-HD), 3.5 hours post-dose with HD, 5 hours post-dose with HD, pre-end of HD, 30 min post-HD, 1 hour post-HD, 2 hours post-HD, 12 hours post-dose, 24 hours post-dose, and 48 hours post-dose.
|
Groups A to D & Group E: Period 2: Pre-dose and 0.5, EOI, 1.5, 2, 3, 6, 12, 24, 48, and 72 hours post-dose
|
|
Cumulative Amount of MK-6183 Excreted in Urine or Dialysate (Ae)
大体时间：Groups A to D (urine): 0 to 24, 24 to 48, and 48 to 72 hours post-dose; Group E (dialysate): 0 to 1, 1 to 2, 2 to 3, and 3 to 4 hours after starting HD
|
Ae is the cumulative amount of drug excreted unchanged in urine or dialysate.
For Groups A, B, C, and D, Ae was assessed in urine.
For Group E: Period 1, Ae was assessed in dialysate (participants in Group E had no detectable urine data) at hourly collection intervals during HD (HD commenced 3 hours after dosing).
|
Groups A to D (urine): 0 to 24, 24 to 48, and 48 to 72 hours post-dose; Group E (dialysate): 0 to 1, 1 to 2, 2 to 3, and 3 to 4 hours after starting HD
|
|
Renal Clearance of MK-6183 (CLr)
大体时间：0 to 24, 24 to 48, and 48 to 72 hours post-dose
|
CLr is the clearance of drug from plasma via the kidneys.
Only data from Groups A, B, C, and D is presented; participants in Group E (Period 1) had no detectable urine data.
Data for Group E: Period 1 are presented below in the dialysate clearance measure.
|
0 to 24, 24 to 48, and 48 to 72 hours post-dose
|
|
Dialysate Clearance of MK-6183 (CLd)
大体时间：0 to 1, 1 to 2, 2 to 3, and 3 to 4 hours after starting HD
|
CLd is the amount of drug cleared from plasma via dialysis.
Only data collected during HD (Group E: Period 1) is presented (HD commenced 3 hours after dosing).
|
0 to 1, 1 to 2, 2 to 3, and 3 to 4 hours after starting HD
|
|
Fraction of the Administered Dose of MK-6183 Excreted Unchanged in Urine or Dialysate (Fe)
大体时间：Groups A to D (urine): 0 to 24, 24 to 48, and 48 to 72 hours post-dose; Group E (dialysate): 0 to 1, 1 to 2, 2 to 3, and 3 to 4 hours after starting HD
|
Fe is the fraction (percentage) of the administered dose that was excreted unchanged in urine (Groups A to D) or dialysate (Group E: Period 1; HD commenced 3 hours after dosing).
|
Groups A to D (urine): 0 to 24, 24 to 48, and 48 to 72 hours post-dose; Group E (dialysate): 0 to 1, 1 to 2, 2 to 3, and 3 to 4 hours after starting HD
|
次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Number of Participants Experiencing an Adverse Event (AE)
大体时间：Up to 12 days
|
An AE is any untoward medical occurrence in a participant administered a pharmaceutical product that does not necessarily have to have a causal relationship with this treatment.
|
Up to 12 days
|
|
Number of Participants Discontinuing From the Study Due to an AE
大体时间：Up to 12 days
|
An AE is any untoward medical occurrence in a participant administered a pharmaceutical product that does not necessarily have to have a causal relationship with this treatment.
|
Up to 12 days
|
合作者和调查者
在这里您可以找到参与这项研究的人员和组织。
研究记录日期
这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。
研究主要日期
学习开始 (实际的)
2014年12月11日
初级完成 (实际的)
2015年4月13日
研究完成 (实际的)
2015年4月20日
研究注册日期
首次提交
2014年12月12日
首先提交符合 QC 标准的
2015年1月14日
首次发布 (估计)
2015年1月19日
研究记录更新
最后更新发布 (实际的)
2019年2月18日
上次提交的符合 QC 标准的更新
2019年2月13日
最后验证
2019年2月1日
更多信息
此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.
MK-6183的临床试验
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