End-Stage Kidney Disease (ESKD), End-Stage Renal Disease (ESRD), Kidney Failure, Chronic
Conditions
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.
Interventions
BIOLOGICALMK-2060
Lyophilized powder diluted in normal saline for IV infusion
DRUGPlacebo
IV infusion
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Double blind
Eligibility
Sex/Gender
ALL
Age
50 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experienced 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 experienced an AE is reported. |
| Number of Participants Who Discontinued 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 discontinued study due to an AE is reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-Time Curve of MK-2060 From Time 0 to 168 Hours Postdose (AUC0-168) | 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 | Blood samples were 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 | 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 | Blood samples were 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, 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 | Blood samples were 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 | 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 | Blood samples were collected at specified intervals for the determination of Tmax. Tmax is defined as time to the maximum concentration of MK-2060 reached. |
| Area Under the Concentration-Time Curve of MK-2060 From Time 0 to Infinity (AUC 0-inf) | 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 | Blood samples were collected at specified intervals for the determination of AUC0-inf. AUC0-inf is defined as the area under the concentration-time curve of MK-2060 from time zero to infinity. |
| Terminal Half-Life (t ½) of MK-2060 | 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 | Blood samples were 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 | 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 | Blood samples were 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 | 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 | Blood samples were 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 168 hours post dose | Blood samples were collected for the determination of aPTT. Change from baseline in aPTT up to 168 hours post dose (pre dialysis) is reported. |
| Time of the Last Measurable Plasma Concentration (Tlast) of MK-2060 | 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 | Blood samples were collected at specified intervals for the determination of Tlast. Tlast is defined as the time to the last measurable concentration of MK-2060 reached. |
| Area Under the Plasma Concentration-Time Curve of MK-2060 From Time 0 to Last (AUC0-last) | 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 | Blood samples were 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. |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| MK-2060 Participants received MK-2060 50 mg via a single intravenous (IV) infusion over 60 minutes. | 12 |
| Placebo Participants received a single IV saline infusion over 60 minutes. | 5 |
| Total | 17 |
Baseline characteristics
| Characteristic | Placebo | Total | MK-2060 |
|---|---|---|---|
| Age, Continuous | 66.2 Years STANDARD_DEVIATION 8.3 | 69.0 Years STANDARD_DEVIATION 7.5 | 70.2 Years STANDARD_DEVIATION 7.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 17 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 5 Participants | 17 Participants | 12 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 1 Participants | 4 Participants | 3 Participants |
| Sex: Female, Male Male | 4 Participants | 13 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 5 |
| other Total, other adverse events | 9 / 12 | 4 / 5 |
| serious Total, serious adverse events | 3 / 12 | 1 / 5 |
Outcome results
Primary
Number of Participants Who Discontinued Study Due to an AE
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 discontinued study due to an AE is reported.
Time frame: Up to approximately 164 days
Population: All participants who received at least one dose of treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| MK-2060 | Number of Participants Who Discontinued Study Due to an AE | 0 Participants |
| Placebo | Number of Participants Who Discontinued Study Due to an AE | 0 Participants |
Primary
Number of Participants Who Experienced an Adverse Event (AE)
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 experienced an AE is reported.
Time frame: Up to approximately 164 days
Population: All participants who received at least one dose of treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| MK-2060 | Number of Participants Who Experienced an Adverse Event (AE) | 10 Participants |
| Placebo | Number of Participants Who Experienced an Adverse Event (AE) | 4 Participants |
Secondary
Area Under the Concentration-Time Curve of MK-2060 From Time 0 to 168 Hours Postdose (AUC0-168)
Blood samples were 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.
Time frame: 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
Population: All participants who were compliant with the study procedures and have available data from at least one MK-2060 treatment were included.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| MK-2060 | Area Under the Concentration-Time Curve of MK-2060 From Time 0 to 168 Hours Postdose (AUC0-168) | 10100 hours*nmol/L | Geometric Coefficient of Variation 23.4 |
Secondary
Area Under the Concentration-Time Curve of MK-2060 From Time 0 to Infinity (AUC 0-inf)
Blood samples were collected at specified intervals for the determination of AUC0-inf. AUC0-inf is defined as the area under the concentration-time curve of MK-2060 from time zero to infinity.
Time frame: 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
Population: All participants who were compliant with the study procedures and have available data from at least one MK-2060 treatment were included.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| MK-2060 | Area Under the Concentration-Time Curve of MK-2060 From Time 0 to Infinity (AUC 0-inf) | 35000 hours*nmol/L | Geometric Coefficient of Variation 31.8 |
Secondary
Area Under the Plasma Concentration-Time Curve of MK-2060 From Time 0 to Last (AUC0-last)
Blood samples were 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.
Time frame: 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
Population: All participants who were compliant with the study procedures and have available data from at least one MK-2060 treatment were included.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| MK-2060 | Area Under the Plasma Concentration-Time Curve of MK-2060 From Time 0 to Last (AUC0-last) | 34500 hours*nmol/L | Geometric Coefficient of Variation 31.8 |
Secondary
Change From Baseline in Activated Partial Thromboplastin Time (aPTT)
Blood samples were collected for the determination of aPTT. Change from baseline in aPTT up to 168 hours post dose (pre dialysis) is reported.
Time frame: Baseline and 168 hours post dose
Population: All participants who were compliant with the study procedures and have available data from at least one treatment were included.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| MK-2060 | Change From Baseline in Activated Partial Thromboplastin Time (aPTT) | 2.45 Fold-Change from baseline |
| Placebo | Change From Baseline in Activated Partial Thromboplastin Time (aPTT) | 0.97 Fold-Change from baseline |
90% CI: [2.24, 2.82]
Secondary
Clearance (CL) of MK-2060
Blood samples were 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.
Time frame: 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
Population: All participants who were compliant with the study procedures and have available data from at least one MK-2060 treatment were included.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| MK-2060 | Clearance (CL) of MK-2060 | 0.00964 Liters/hour | Geometric Coefficient of Variation 31.8 |
Secondary
Concentration at 168 Hours (C168) Postdose of MK-2060
Blood samples were 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 frame: 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
Population: All participants who were compliant with the study procedures and have available data from at least one MK-2060 treatment were included.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| MK-2060 | Concentration at 168 Hours (C168) Postdose of MK-2060 | 39.0 nmol/L | Geometric Coefficient of Variation 30.9 |
Secondary
Maximum Concentration (Cmax) of MK-2060
Blood samples were collected at specified intervals for the determination of Cmax. Cmax is defined as the maximum concentration of MK-2060 reached.
Time frame: 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
Population: All participants who were compliant with the study procedures and have available data from at least one MK-2060 treatment were included.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| MK-2060 | Maximum Concentration (Cmax) of MK-2060 | 110 nmol/L | Geometric Coefficient of Variation 26 |
Secondary
Terminal Half-Life (t ½) of MK-2060
Blood samples were 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.
Time frame: 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
Population: All participants who were compliant with the study procedures and have available data from at least one MK-2060 treatment were included.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| MK-2060 | Terminal Half-Life (t ½) of MK-2060 | 22.7 Days | Geometric Coefficient of Variation 18.2 |
Secondary
Time of the Last Measurable Plasma Concentration (Tlast) of MK-2060
Blood samples were collected at specified intervals for the determination of Tlast. Tlast is defined as the time to the last measurable concentration of MK-2060 reached.
Time frame: 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
Population: All participants who were compliant with the study procedures and have available data from at least one MK-2060 treatment were included.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| MK-2060 | Time of the Last Measurable Plasma Concentration (Tlast) of MK-2060 | 3407.34 hours |
Secondary
Time to Maximum Concentration (Tmax) of MK-2060
Blood samples were collected at specified intervals for the determination of Tmax. Tmax is defined as time to the maximum concentration of MK-2060 reached.
Time frame: 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
Population: All participants who were compliant with the study procedures and have available data from at least one MK-2060 treatment were included.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| MK-2060 | Time to Maximum Concentration (Tmax) of MK-2060 | 1.03 hours |
Secondary
Volume of Distribution (Vz) of MK-2060
Blood samples were collected at specified intervals for the determination of Vz. Vz is the apparent volume of distribution during the terminal phase.
Time frame: 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
Population: All participants who were compliant with the study procedures and have available data from at least one MK-2060 treatment were included.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| MK-2060 | Volume of Distribution (Vz) of MK-2060 | 7.58 Liters | Geometric Coefficient of Variation 28.5 |