A Single-and Multiple Dose Study to Assess the Safety, Pharmacokinetics and Pharmacodynamics of Subcutaneous MK-2060 in Participants With Chronic and/or End-Stage Kidney Disease
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 14
- 试验地点
- 4
- 主要终点
- Part 1: Number of Participants Who Experience One or More Bleeding Related Adverse Events (AE)
研究概览
简要总结
This was intended as a three-part study of MK-2060 in participants with chronic and/or end-stage kidney disease (Parts 2 and 3 were not initiated due to reasons not related to safety). The purpose of Part 1 of the study was to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of a single subcutaneous dose of MK-2060 in stage 4 chronic kidney disease (CKD4) [Part2 was intended to evaluate multiple subcutaneous doses in CKD4 participants and Part 3 was intended to evaluate a single subcutaneous dose of MK-2060 in participants with end-stage kidney disease (ESRD)]. The primary hypothesis for Part 1 was that the true geometric mean of the area under the concentration-time curve from 0 to infinity (AUC0-inf) after a single-dose of MK-2060 in adult CKD4 participants would be at least 11300 nM*hr.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •At the time of screening, has stage 4 or 5 chronic kidney disease (Parts 1 and 2) or end-state kidney disease on peritoneal dialysis (Part 3).
- •Has a body mass index (BMI) ≥ 18 and ≤ 45 kg/m^2.
排除标准
- •Has a history of cancer, including adenocarcinoma, except adequately treated non-melanomatous skin carcinoma or carcinoma in situ of the cervix or other malignances which have been successfully treated ≥ 5 years prior to prestudy with appropriate follow-up.
- •Has a history of deep vein thrombosis or pulmonary embolism, a history of vascular access thrombosis within 1 month prior to enrollment, or has a personal or family history of bleeding disorder.
- •Has a history of gastrointestinal (GI) bleeding, duodenal polyps, or gastric ulcer in the last 5 years or severe hemorrhoidal bleed in the last 3 months.
- •Has a history of or current frequent epistaxis within the last 3 months or active gingivitis.
- •Has ongoing anticoagulant therapy or antiplatelet therapy. Aspirin is permitted.
- •Has planned significant dental procedures at the time of screening or pre-dose or other planned surgical procedures within duration of participation of study.
- •Is positive for hepatitis B surface antigen or human immunodeficiency virus (HIV).
- •Has had major surgery and/or donated or lost 1 unit of blood (approximately 500 mL) within 4 weeks prior to the pre-study visit.
- •Has a history (participant recall) of receiving any human immunoglobulin preparation such as intravenous immunoglobulin (IVIG) or RhoGAM within the last year.
- •Has a history (participant recall) of receiving any biological therapy (including human blood products or monoclonal antibodies; excluding erythropoietin and insulin) within the last 3 months or vaccination within the last 1 month, except the seasonal flu and pneumococcal vaccine or COVID-19 vaccine.
研究组 & 干预措施
MK-2060 30 mg
Participants received MK-2060 30 mg administered as a single subcutaneous dose on Day 1.
干预措施: MK-2060 (Biological)
Placebo
Participants received placebo (normal saline) administered as a single subcutaneous dose on Day 1.
干预措施: Placebo (Drug)
结局指标
主要结局
Part 1: Number of Participants Who Experience One or More Bleeding Related Adverse Events (AE)
时间窗: Up to approximately 104 days
Bleeding related AEs will include any sign or symptom of bleeding, even if not requiring intervention by a medical/healthcare professional, as well as clinically relevant nonmajor bleeding or major bleeding.
Part 2: Number of Participants Who Experience One or More Bleeding Related AEs
时间窗: Up to approximately 144 days
Bleeding related AEs include any sign or symptom of bleeding, even if not requiring intervention by a medical/healthcare professional, as well as clinically relevant nonmajor bleeding or major bleeding.
Part 3: Number of Participants Who Experience One or More Bleeding Related AEs
时间窗: Up to approximately 104 days
Bleeding related AEs will include any sign or symptom of bleeding, even if not requiring intervention by a medical/healthcare professional, as well as clinically relevant nonmajor bleeding or major bleeding.
Part 1: Number of Participants Who Experience One or More AEs
时间窗: Up to approximately 104 days
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.
Part 2: Number of Participants Who Experience One or More AEs
时间窗: Up to approximately 144 days
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.
Part 3: Number of Participants Who Experience One or More AEs
时间窗: Up to approximately 104 days
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.
Part 1: Number of Participants Who Discontinue Study Treatment to an AE
时间窗: Up to approximately 104 days
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.
Part 2: Number of Participants Who Discontinue Study Treatment Due to an AE
时间窗: Up to approximately 144 days
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.
Part 3: Number of Participants Who Discontinue Study Due to an AE
时间窗: Up to approximately 104 days
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.
Part 1: Area Under the Concentration-Time Curve From 0 to Infinity (AUC0-inf) of MK-2060
时间窗: Day 1: pre-dose, 1 and 12 hours post-dose; once daily on Days 2, 3, 6, 8, 11, 14, 21, 28, 60, and 90 post-dose
Blood was collected to determine the AUC0-inf of MK-2060 in plasma.
Part 2: AUC0-inf of MK-2060
时间窗: Days 1, 2, 4, 8, 15, and 22: pre-dose; once daily on Days 10, 17, 26, 29, 35, 42, 49, 63, 81, 111, and 130 post-dose
Blood was to be collected at pre-specified time points to determine the AUC0-inf of MK-2060 in plasma.
Part 3: AUC0-inf of MK-2060
时间窗: Day 1: pre-dose, 1 and 12 hours post-dose; once daily on Days 2, 3, 6, 8, 11, 14, 21, 28, 42, 60, 90, and 120 post-dose
Blood was to be collected at pre-specified time points to determine the AUC0-inf of MK-2060 in plasma.
Part 2: AUC0-168 of MK-2060
时间窗: Pre-dose, 24, 72, and 168 hours post-dose
Blood was to be collected at pre-specified time points to determine the AUC0-168 of MK-2060 in plasma from 0 to 168 hours.
Part 1: Area Under the Concentration-Time Curve From Time 0 to 168 Hours (AUC0-168) of MK-2060
时间窗: Pre-dose, 1, 12, 24, 48, 120, and 168 hours post-dose
Blood was collected to determine the AUC0-168 of MK-2060 in plasma.
Part 3: AUC0-168 of MK-2060
时间窗: Pre-dose, 1, 12, 24, 48, 120, and 168 hours post-dose
Blood was to be collected at pre-specified time points to determine the AUC0-168 of MK-2060 in plasma from 0 to 168 hours.
Part 1: Maximum Plasma Concentration (Cmax) of MK-2060
时间窗: Day 1: pre-dose, 1 and 12 hours post-dose; once daily on Days 2, 3, 6, 8, 11, 14, 21, 28, 60, and 90 post-dose
Blood was collected at pre-specified time points to determine the Cmax of MK-2060 in plasma.
Part 2: Cmax of MK-2060
时间窗: Days 1, 2, 4, 8, 15, and 22: pre-dose; once daily on Days 10, 17, 26, 29, 35, 42, 49, 63, 81, 111, and 130 post-dose
Blood was to be collected at pre-specified time points to determine the Cmax of MK-2060 in plasma.
Part 3: Cmax of MK-2060
时间窗: Day 1: pre-dose, 1 and 12 hours post-dose; once daily on Days 2, 3, 6, 8, 11, 14, 21, 28, 42, 60, 90, and 120 post-dose
Blood was to be collected at pre-specified time points to determine the Cmax of MK-2060 in plasma.
Part 2: C168 of MK-2060
时间窗: 168 hours post-dose
Blood was to be collected at 168 hours post-dose to determine the C168 of MK-2060 in plasma.
Part 1: Plasma Concentration at 168 Hours (C168) of MK-2060
时间窗: 168 hours post-dose
Blood was collected at 168 hours post-dose to determine the C168 of MK-2060 in plasma.
Part 3: C168 of MK-2060
时间窗: 168 hours post-dose
Blood was to be collected at 168 hours post-dose to determine the C168 of MK-2060 in plasma.
Part 1: Time to Maximum Plasma Concentration (Tmax) of MK-2060
时间窗: Day 1: pre-dose, 1 and 12 hours post-dose; once daily on Days 2, 3, 6, 8, 11, 14, 21, 28, 60, and 90 post-dose
Blood was collected at pre-specified time points to determine the Tmax of MK-2060 in plasma.
Part 2: Tmax of MK-2060
时间窗: Days 1, 2, 4, 8, 15, and 22: pre-dose; once daily on Days 10, 17, 26, 29, 35, 42, 49, 63, 81, 111, and 130 post-dose
Blood was to be collected at pre-specified time points to determine the Tmax of MK-2060 in plasma.
Part 3: Tmax of MK-2060
时间窗: Day 1: pre-dose, 1 and 12 hours post-dose; once daily on Days 2, 3, 6, 8, 11, 14, 21, 28, 42, 60, 90, and 120 post-dose
Blood was to be collected at pre-specified time points to determine the Tmax of MK-2060 in plasma.
Part 1: Terminal Half Life (t1/2) of MK-2060
时间窗: Day 1: pre-dose, 1 and 12 hours post-dose; once daily on Days 2, 3, 6, 8, 11, 14, 21, 28, 60, and 90 post-dose
Blood was collected at pre-specified time points to determine the terminal t1/2 of MK-2060 in plasma.
Part 2: t1/2 of MK-2060
时间窗: Days 1, 2, 4, 8, 15, and 22: pre-dose; once daily on Days 10, 17, 26, 29, 35, 42, 49, 63, 81, 111, and 130 post-dose
Blood was to be collected at pre-specified time points to determine the terminal t1/2 of MK-2060 in plasma.
Part 3: t1/2 of MK-2060
时间窗: Day 1: pre-dose, 1 and 12 hours post-dose; once daily on Days 2, 3, 6, 8, 11, 14, 21, 28, 42, 60, 90, and 120 post-dose
Blood was to be collected at pre-specified time points to determine the terminal t1/2 of MK-2060 in plasma.
Part 1: Apparent Total Clearance (CL/F) of MK-2060
时间窗: Day 1: pre-dose, 1 and 12 hours post-dose; once daily on Days 2, 3, 6, 8, 11, 14, 21, 28, 60, and 90 post-dose
Blood was collected at pre-specified time points to determine the CL/F of MK-2060 in plasma.
Part 2: CL/F of MK-2060
时间窗: Days 1, 2, 4, 8, 15, and 22: pre-dose; once daily on Days 10, 17, 26, 29, 35, 42, 49, 63, 81, 111, and 130 post-dose
Blood was to be collected at pre-specified time points to determine the CL/F of MK-2060 in plasma.
Part 3: CL/F of MK-2060
时间窗: Day 1: pre-dose, 1 and 12 hours post-dose; once daily on Days 2, 3, 6, 8, 11, 14, 21, 28, 42, 60, 90, and 120 post-dose
Blood was to be collected at pre-specified time points to determine the CL/F of MK-2060 in plasma.
Part 1: Apparent Volume of Distribution (Vz/F) of MK-2060
时间窗: Day 1: pre-dose, 1 and 12 hours post-dose; once daily on Days 2, 3, 6, 8, 11, 14, 21, 28, 60, and 90 post-dose
Blood was collected at pre-specified time points to determine the Vz/F of MK-2060 in plasma
Part 2: Vz/F of MK-2060
时间窗: Days 1, 2, 4, 8, 15, and 22: pre-dose; once daily on Days 10, 17, 26, 29, 35, 42, 49, 63, 81, 111, and 130 post-dose
Blood was to be collected at pre-specified time points to determine the Vz/F of MK-2060 in plasma
Part 3: Vz/F of MK-2060
时间窗: Day 1: pre-dose, 1 and 12 hours post-dose; once daily on Days 2, 3, 6, 8, 11, 14, 21, 28, 42, 60, 90, and 120 post-dose
Blood was to be collected at pre-specified time points to determine the Vz/F of MK-2060 in plasma
次要结局
- Part 2: Percent Change From Baseline in aPTT of MK-2060(Day 1 (1 hr and 12 hrs postdose) and Days 2, 3, 6, 8, 11, 14, 21, 28, 60, and Post Study (Day 90))
- Part 1: Mean Fold Change From Baseline in Activated Partial Thromboplastin Time (aPTT) of MK-2060(Day 1 (1 hr and 12 hrs postdose) and Days 2, 3, 6, 8, 11, 14, 21, 28, 60, and Post Study (Day 90))
- Part 3: Percent Change From Baseline in aPTT of MK-2060(Day 1 (1 hr and 12 hrs postdose) and Days 2, 3, 6, 8, 11, 14, 21, 28, 60, and Post Study (Day 90))