Single Dose Study of MK-2060 to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics in Older Japanese Participants on Dialysis (MK-2060-012)
Study Details
Study Description
Brief Summary
The purpose of this study is to assess the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of MK-2060 after a single dose intravenous (IV) administration in Japanese older participants with end stage renal disease (ESRD) on dialysis. There is no primary hypothesis for this study.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: MK-2060 Participants receive MK-2060 50 mg via a single intravenous (IV) infusion over 60-minutes. |
Biological: MK-2060
Lyophilized powder diluted in normal saline for IV infusion
|
| Placebo Comparator: Placebo Participants receive a single IV saline infusion over 60 minutes. |
Drug: Placebo
IV infusion
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Number of Participants Who Experience an Adverse Event (AE) [Up to approximately 164 days]
An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the study drug whether or not it is considered related to the study drug. The number of participants who experience an AE will be reported.
- Number of Participants Who Discontinue Study Due to an AE [Up to approximately 164 days]
An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the study drug whether or not it is considered related to the study drug. The number of participants who discontinue study due to an AE will be reported.
Secondary Outcome Measures
- Area Under the Concentration-Time Curve of MK-2060 From Time 0 to Infinity (AUC 0-inf) [Day 1-3: Predose and 1, 12, 24, 48 and 52 hours postdose; once daily on Days 5, 12, 15, 22, 60, 90, 150: postdose; and twice daily on Days 8, 29, 120: pre- and post-dialysis]
Blood samples will be collected at specified intervals for the determination of AUC0-inf. AUC0-inf is defined as the area under the concentration-time curve of pembrolizumab from time zero to infinity.
- Area Under the Plasma Concentration-Time Curve of MK-2060 From Time 0 to Last (AUC0-last) [Day 1-3: Predose and 1, 12, 24, 48 and 52 hours postdose; once daily on Days 5, 12, 15, 22, 60, 90, 150: postdose; and twice daily on Days 8, 29, 120: pre- and post-dialysis]
Blood samples will be collected at specified intervals for the determination of AUC0-last. AUC0-last is defined as the area under the plasma concentration-time curve from time zero to time of last measurable concentration of MK-2060.
- Area Under the Concentration-Time Curve of MK-2060 From Time 0 to 168 Hours Postdose (AUC0-168) [Predose and 1, 12, 24, 48, 52, 96, and 168 hours postdose]
Blood samples will be collected at specified intervals for the determination of AUC0-168. AUC0-168 is defined as the area under the concentration-time curve of MK-2060 from time zero to 168 hours.
- Maximum Concentration (Cmax) of MK-2060 [Day 1-3: Predose and 1, 12, 24, 48 and 52 hours postdose; once daily on Days 5, 12, 15, 22, 60, 90, 150: postdose; and twice daily on Days 8, 29, 120: pre- and post-dialysis]
Blood samples will be collected at specified intervals for the determination of Cmax. Cmax is defined as the maximum concentration of MK-2060 reached.
- Concentration at 168 Hours (C168) Postdose of MK-2060 [Predose and 1, 12, 24, 48, 52, 96, and 168 hours postdose]
Blood samples will be collected at specified intervals for the determination of C168. C168 is defined as the maximum concentration of MK-2060 reached at 168 hours postdose.
- Time to Maximum Concentration (Tmax) of MK-2060 [Day 1-3: Predose and 1, 12, 24, 48 and 52 hours postdose; once daily on Days 5, 12, 15, 22, 60, 90, 150: postdose; and twice daily on Days 8, 29, 120: pre- and post-dialysis]
Blood samples will be collected at specified intervals for the determination of Tmax. Tmax is defined as time to the maximum concentration of MK-2060 reached.
- Time of the Last Measurable Plasma Concentration (Tlast) of MK-2060 [Day 1-3: Predose and 1, 12, 24, 48 and 52 hours postdose; once daily on Days 5, 12, 15, 22, 60, 90, 150: postdose; and twice daily on Days 8, 29, 120: pre- and post-dialysis]
Blood samples will be collected at specified intervals for the determination of Tlast. Tlast is defined as the time to the last measurable concentration of MK-2060 reached.
- Terminal Half-Life (t ½) of MK-2060 [Day 1-3: Predose and 1, 12, 24, 48 and 52 hours postdose; once daily on Days 5, 12, 15, 22, 60, 90, 150: postdose; and twice daily on Days 8, 29, 120: pre- and post-dialysis]
Blood samples will be collected at specified intervals for the determination of t½. t½ is defined as the time required to divide the MK-2060 plasma concentration by two after reaching pseudo-equilibrium, following a single dose of MK-2060.
- Clearance (CL) of MK-2060 [Day 1-3: Predose and 1, 12, 24, 48 and 52 hours postdose; once daily on Days 5, 12, 15, 22, 60, 90, 150: postdose; and twice daily on Days 8, 29, 120: pre- and post-dialysis]
Blood samples will be collected at specified intervals for the determination of CL. CL is the volume of plasma from which the study drug is completely removed per unit time.
- Volume of Distribution (Vz) of MK-2060 [Day 1-3: Predose and 1, 12, 24, 48 and 52 hours postdose; once daily on Days 5, 12, 15, 22, 60, 90, 150: postdose; and twice daily on Days 8, 29, 120: pre- and post-dialysis]
Blood samples will be collected at specified intervals for the determination of Vz. Vz is the apparent volume of distribution during the terminal phase.
- Change From Baseline in Activated Partial Thromboplastin Time (aPTT) [Baseline and up to 150 days]
Blood samples will be collected for the determination of aPTT. Change from baseline in aPTT up to 150 days will be reported.
Eligibility Criteria
Criteria
Inclusion Criteria:
The main inclusion criteria include but are not limited to the following:
-
Japanese descent with all 2 biological parents of Japanese descent
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On hemodialysis (HD) or hemodiafiltration (HDF) with single-pool Kt/V (spKt/V) ≥1.2, using arteriovenous (AV) fistula or AV graft ≥3 months prior to Screening 1 at a healthcare center, and is on the same dialysis regimen ≥2 weeks prior to Screening 1
-
Be judged to plan to continue or anticipate the use of the current AV fistula or AV graft until the poststudy visit
Exclusion Criteria:
The main exclusion criteria include but are not limited to the following:
-
On peritoneal dialysis or other dialysis modalities except for HD and HDF
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History of deep vein thrombosis or pulmonary embolism
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History of vascular access thrombosis within 1 month prior to Screening 1
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Personal or family history of bleeding disorder
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History of GI bleeding, duodenal polyps or active gastroduodenal ulcer within 5 years prior to Screening 1, or history of severe hemorrhoidal bleed within 3 months prior to Screening 1
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History of frequent epistaxis within 3 months prior to Screening 1 or active gingivitis
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At the time of screening or predose, planned significant dental procedures, or other planned surgical procedures within duration of participation in the trial
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History of receiving any human immunoglobulin preparation such as intravenous immunoglobulin (IVIG) or a brand of Rho(D) immune globulin (RhoGAM) within 1 year prior to Screening 1
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History of receiving any biological therapy within 3 months prior to Screening 1, or vaccination within 1 month prior to the dose of study intervention
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Requires or anticipates requiring the use of following prohibited medications until the poststudy visit: anticoagulants, antiplatelet medications and non-steroidal anti-inflammatory drugs (NSAIDs)
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Participated in another investigational study within 1 month prior to Screening 1
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Has blood coagulation test (activated partial thromboplastin time [aPTT] or prothrombin time [PT]) above 1.2X upper limit of normal (ULN) at Screening 1 from the central laboratory for safety
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Merck Sharp & Dohme LLC
Investigators
- Study Director: Medical Director, Merck Sharp & Dohme LLC
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 2060-012
- MK-2060-012