Clinical trial NCT05769595: Single Dose Study of MK-2060 to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics in Older Japanese Participants on Dialysis (MK-2060-012)
Official title: A Single-dose Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of MK-2060 in Japanese Older Participants With End-stage Renal Disease on Dialysis.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: End-Stage Renal Disease (ESRD)
End-Stage Kidney Disease (ESKD)
Kidney Failure, Chronic
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2023-03-15
Enrollment: 17
Sex: ALL
Minimum age (years): 50
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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
* 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
* History of deep vein thrombosis or pulmonary embolism
* History of vascular access thrombosis within 1 month prior to Screening 1
* Personal or family history of bleeding disorder
* 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
* History of frequent epistaxis within 3 months prior to Screening 1 or active gingivitis
* At the time of screening or predose, planned significant dental procedures, or other planned surgical procedures within duration of participation in the trial
* 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
* 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
* Requires or anticipates requiring the use of following prohibited medications until the poststudy visit: anticoagulants, antiplatelet medications and non-steroidal anti-inflammatory drugs (NSAIDs)
* Participated in another investigational study within 1 month prior to Screening 1
* 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

Primary outcomes:
measure: Number of Participants Who Experienced an Adverse Event (AE)
timeFrame: Up to approximately 164 days
measure: Number of Participants Who Discontinued Study Due to an AE
timeFrame: Up to approximately 164 days
Secondary outcomes:
measure: Area Under the Concentration-Time Curve of MK-2060 From Time 0 to Infinity (AUC 0-inf)
timeFrame: Predose, 1, 12, 24, 48 and 52 hours postdose; 5, 12, 15, 22, 60, 90, and up to 157 days post dose; and twice daily on Days 8, 29, 120: pre- and post-dialysis
measure: Area Under the Plasma Concentration-Time Curve of MK-2060 From Time 0 to Last (AUC0-last)
timeFrame: Predose, 1, 12, 24, 48 and 52 hours postdose; 5, 12, 15, 22, 60, 90, and up to 157 days post dose; and twice daily on Days 8, 29, 120: pre- and post-dialysis
measure: Area Under the Concentration-Time Curve of MK-2060 From Time 0 to 168 Hours Postdose (AUC0-168)
timeFrame: Predose, 1, 12, 24, 48 and 52 hours postdose; 5, 12, 15, 22, 60, 90, and up to 157 days post dose; and twice daily on Days 8, 29, 120: pre- and post-dialysis
measure: Maximum Concentration (Cmax) of MK-2060
timeFrame: Predose, 1, 12, 24, 48 and 52 hours postdose; 5, 12, 15, 22, 60, 90, and up to 157 days post dose; and twice daily on Days 8, 29, 120: pre- and post-dialysis
measure: Concentration at 168 Hours (C168) Postdose of MK-2060
timeFrame: Predose, 1, 12, 24, 48 and 52 hours postdose; 5, 12, 15, 22, 60, 90, and up to 157 days post dose; and twice daily on Days 8, 29, 120: pre- and post-dialysis
measure: Time to Maximum Concentration (Tmax) of MK-2060
timeFrame: Predose, 1, 12, 24, 48 and 52 hours postdose; 5, 12, 15, 22, 60, 90, and up to 157 days post dose; and twice daily on Days 8, 29, 120: pre- and post-dialysis
measure: Time of the Last Measurable Plasma Concentration (Tlast) of MK-2060
timeFrame: Predose, 1, 12, 24, 48 and 52 hours postdose; 5, 12, 15, 22, 60, 90, and up to 157 days post dose; and twice daily on Days 8, 29, 120: pre- and post-dialysis
measure: Terminal Half-Life (t ½) of MK-2060
timeFrame: Predose, 1, 12, 24, 48 and 52 hours postdose; 5, 12, 15, 22, 60, 90, and up to 157 days post dose; and twice daily on Days 8, 29, 120: pre- and post-dialysis
measure: Clearance (CL) of MK-2060
timeFrame: Predose, 1, 12, 24, 48 and 52 hours postdose; 5, 12, 15, 22, 60, 90, and up to 157 days post dose; and twice daily on Days 8, 29, 120: pre- and post-dialysis
measure: Volume of Distribution (Vz) of MK-2060
timeFrame: Predose, 1, 12, 24, 48 and 52 hours postdose; 5, 12, 15, 22, 60, 90, and up to 157 days post dose; and twice daily on Days 8, 29, 120: pre- and post-dialysis
measure: Change From Baseline in Activated Partial Thromboplastin Time (aPTT)
timeFrame: Baseline and 168 hours post dose
Other outcomes:
Locations:
city: Kasugai
country: Japan
facility: Kasugai Municipal Hospital ( Site 1203)
state: Aichi
city: Nagoya
country: Japan
facility: Chubu Rosai Hospital ( Site 1202)
state: Aichi
city: Nagoya
country: Japan
facility: Kojunkai Daido Hospital ( Site 1207)
state: Aichi
city: Maebashi
country: Japan
facility: Jomo Ohashi Clinic ( Site 1210)
state: Gunma
city: Kasama
country: Japan
facility: Ibaraki Prefectural Central Hospital ( Site 1211)
state: Ibaraki
city: Kamakura
country: Japan
facility: Shonan Kamakura General Hospital ( Site 1205)
state: Kanagawa
city: Matsumoto
country: Japan
facility: Matsumoto City Hospital ( Site 1209)
state: Nagano
city: Beppu
country: Japan
facility: Keiaikai Nakamura Hospital ( Site 1213)
state: Oita
city: Kusatsu
country: Japan
facility: Omi Fureai Hospital ( Site 1204)
state: Shiga
city: Ota
country: Japan
facility: Ikegami General Hospital ( Site 1206)
state: Tokyo
city: Fukuoka
country: Japan
facility: Japanese Red Cross Fukuoka Hospital ( Site 1214)
city: Yamagata
country: Japan
facility: Yamagata Tokushukai Hospital ( Site 1201)
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: