臨床研究等提出・公開システム

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.

Single Dose Study of MK-2060 in Japanese Older Participants on Dialysis

17

MK-2060 group - Mean Age: 70.2 years - Sex: Female 25.0%, Male 75.0% - Race: Asian 100.0% Placebo group - Mean Age: 66.2 years - Sex: Female 20.0%, Male 80.0% - Race: Asian 100.0%

MK-2060 group - Started: 12 participants - Completed: 12 participants - Not Completed: 0 participant Placebo group - Started: 5 participants - Completed: 5 participants - Not Completed: 0 participant

Percentage of all-cause mortality - MK-2060 group: 0.00% (0/12 participants) - Placebo group: 0.00% (0/5 participants) Percentage of participants with serious adverse events Total - MK-2060 group: 25.00% (3/12 participants) - Placebo group: 20.00% (1/5 participants) Serious adverse events - MK-2060 group: Enteritis infectious (8.33%), Shunt occlusion (8.33%), Shunt stenosis (8.33%), Colon cancer (8.33%) - Placebo group: Mechanical ileus (20.00%), Peripheral arterial occlusive disease (20.00%) Percentage of participants with non-serious adverse events in each treatment group Total - MK-2060 group: 75.00% (9/12 participants) - Placebo group: 80.00% (4/5 participants) Non-serious adverse events - MK-2060 group: Vomiting (16.67%), Nasopharyngitis (16.67%), Contusion (16.67%), Shunt stenosis (16.67%), Occult blood positive (16.67%) , Nephrogenic anaemia (8.33%), Diarrhoea (8.33%), Toothache (8.33%), Oedema peripheral (8.33%), Vaccination site pain (8.33%), COVID-19 (8.33%), Immunisation reaction (8.33%), Bleeding time prolonged (8.33%), Electrocardiogram QT prolonged (8.33%), Back pain (8.33%), Dermatitis contact (8.33%) - Placebo group: Duodenitis (20.00%), Oedema peripheral (20.00%), Pyrexia (20.00%), Nasopharyngitis (20.00%), Immunisation reaction (20.00%), Ligament sprain (20.00%), Lumbar vertebral fracture (20.00%), Hypoglycaemia (20.00%), Intraductal papillary mucinous neoplasm (20.00%), Haematuria (20.00%), Decubitus ulcer (20.00%), Pruritus allergic (20.00%), Hypotension (20.00%), Internal haemorrhage (20.00%)

Primary Outcome Measures Analysis Population Description:All participants who received at least one dose of treatment. 1. Number of Participants Who Experienced an Adverse Event (AE) - MK-2060 group:83.3% (10/12 participants) - Placebo group:80.0% (4/5 participants) Secondary Outcome Measures Analysis Population Description:All participants who received at least one dose of treatment. 1. AUC 0-inf Geometric Mean (Geometric Coefficient of Variation) MK-2060:35000 hours*nmol/L (31.8%) 2. AUC0-last Geometric Mean (Geometric Coefficient of Variation) MK-2060:34500 hours*nmol/L (31.8%) 3. AUC0-168 Geometric Mean (Geometric Coefficient of Variation) MK-2060:10100 hours*nmol/L (23.4%) 4. Cmax Geometric Mean (Geometric Coefficient of Variation) MK-2060:110 nmol/L (26.0%) 5. C168 Geometric Mean (Geometric Coefficient of Variation) MK-2060:39.0 nmol/L (30.9%) 6. Tmax Median (Range) MK-2060:1.03 hours (0.88 to 12.02) 7. Tlast Median (Range) MK-2060:3407.34 hours (2186.65 to 3695.18) 8. t1/2 Geometric Mean (Geometric Coefficient of Variation) MK-2060:22.7 Days (18.2%) 9. CL Geometric Mean (Geometric Coefficient of Variation) MK-2060:0.00964 Liters/hours (31.8%) 10. Vz Geometric Mean (Geometric Coefficient of Variation) MK-2060:7.58 Liters (28.5%) 11. aPTT Fold-Change from baseline at 168 hours postdose (pre-dialysis on Day 8) Geometric Mean (95% Confidence Interval) MK-2060:2.45 (2.27 to 2.63)

Safety Administration of a single 50 mg IV dose of MK-2060 was generally well tolerated in Japanese participants with ESRD on dialysis. PK The median Tmax of MK-2060 was approximately 1 hour after the start of infusion, and the geometric mean t1/2 of MK-2060 was 22.7 days. PD As anticipated based on FXI/FXIa inhibition by MK-2060, aPTT values increased in Japanese participants with ESRD on dialysis.

Yes

https://engagezone.msd.com/

https://jrct.mhlw.go.jp/latest-detail/jRCT2041230025

Tanaka Yoshiyuki

MSD K.K.

KITANOMARU SQUARE,1-13-12,Kudan-kita,Chiyoda-ku,Tokyo 102-8667,Japan

msdjrct@msd.com

MSDJRCT inquiry mailbox

MSD K.K.

KITANOMARU SQUARE,1-13-12,Kudan-kita,Chiyoda-ku,Tokyo 102-8667,Japan

+81-3-6272-1957

msdjrct@msd.com

Complete

June. 13, 2023

Interventional

randomized controlled trial

double blind

placebo control

parallel assignment

treatment purpose

1) Japanese descent with all 2 biological parents of Japanese descent
2) 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
3) Be judged to plan to continue or anticipate the use of the current AV fistula or AV graft until the poststudy visit

1) On peritoneal dialysis or other dialysis modalities except for HD and HDF
2) History of deep vein thrombosis or pulmonary embolism
3) History of vascular access thrombosis within 1 month prior to Screening 1
4) Personal or family history of bleeding disorder
5) 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
6) History of frequent epistaxis within 3 months prior to Screening 1 or active gingivitis
7) At the time of screening or predose, planned significant dental procedures, or other planned surgical procedures within duration of participation in the trial
8) 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
9) 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
10) Requires or anticipates requiring the use of following prohibited medications until the poststudy visit: anticoagulants, antiplatelet medications and non-steroidal anti-inflammatory drugs (NSAIDs)
11) Participated in another investigational study within 1 month prior to Screening 1
12) 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

Both

end-stage renal disease

MK-2060 50 mg, Placebo

1) Number of Participants Who Experience an Adverse Event (AE)
2) Number of Participants Who Discontinue Study Due to an AE

1) Area Under the Concentration-Time Curve of MK-2060 From Time 0 to Infinity (AUC0-inf)
2) Area Under the Plasma Concentration-Time Curve of MK-2060 From Time 0 to Last (AUC0-last)
3) Area Under the Concentration-Time Curve of MK-2060 From Time 0 to 168 Hours Postdose (AUC0-168)
4) Maximum Concentration (Cmax) of MK-2060
5) Concentration at 168 Hours (C168) Postdose of MK-2060
6) Time to Maximum Concentration (Tmax) of MK-2060
7) Time of the Last Measurable Plasma Concentration (Tlast) of MK-2060
8) Terminal Half-Life (t 1/2) of MK-2060
9) Clearance (CL) of MK-2060
10) Volume of Distribution (Vz) of MK-2060
11) Change From Baseline in Activated Partial Thromboplastin Time (aPTT)

+81-52-611-6261

Mar. 07, 2023

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