Renal Impairment
Conditions
Brief summary
The goal of this study is to evaluate the effect of moderate and severe renal impairment (RI) on the pharmacokinetics (PK), safety, and tolerability of MK-8527. There will be no hypothesis testing in the study.
Interventions
DRUGMK-8527
Oral Capsule
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
The main inclusion criteria include but are not limited to the following: Moderate and Severe RI * With the exception of RI, is in sufficient health for study participation. * Has stable renal function. Healthy * Matches mean age to participants with moderate and severe RI. * Has normal renal function.
Exclusion criteria
The main
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration Versus Time Curve From Time 0 to Last Quantifiable Sample (AUC0-last) of MK-8527 in Plasma | Predose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, and 168 hours post dose | Blood samples were collected at pre-specified time points to determine the AUC0-last of MK-8527 in participant's plasma. AUC0 to last of MK-8527 was defined as the area under the concentration-time curve from time 0 to the time of the last quantifiable (above lower limit of quantitation) concentration. AUC0-last was calculated using noncompartmental analysis. |
| Area Under the Concentration Versus Time Curve From Time 0 to Infinity (AUC0-inf) of MK-8527 in Plasma | Predose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, and 168 hours post dose | Blood samples were collected at pre-specified time points to determine the AUC0-inf of MK-8527 in participant's plasma. AUC0-inf was defined as AUC0-last + (Cest,last/λz) where Cest,last was the estimated last measurable concentration, and λz was the apparent first-order terminal elimination rate constant. |
| Maximum Concentration (Cmax) of MK-8527 in Plasma | Predose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, and 168 hours post dose | Blood samples were collected at pre-specified time points to determine the Cmax of MK-8527 in participant's plasma. Cmax was defined as the maximum observed concentration of MK-8527 in plasma after the administration of a given dose. |
| Time to Maximum Concentration (Tmax) of MK-8527 in Plasma | Predose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, and 168 hours post dose | Blood samples were collected at pre-specified time points to determine the tmax of MK-8527 in participant's plasma. Tmax of MK-8527 in plasma was determined by deriving the difference between the time of the blood draw associated with the Cmax and the time of study drug administration |
| Apparent Terminal Half-life (t1/2) of MK-8527 in Plasma | Predose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, and 168 hours post dose | Blood samples were collected at pre-specified time points to determine the t1/2 of MK-8527 in participant's plasma. t1/2 was defined as 0.693/Apparent terminal elimination rate constant (λz). |
| Apparent Clearance (CL/F) of MK-8527 in Plasma | Predose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, and 168 hours post dose | Blood samples were collected at pre-specified time points to determine the CL/F of MK-8527 in participant's plasma. CL/F was defined as dose/(AUC0-inf). |
| Apparent Volume of Distribution During Terminal Phase (Vz/F) of MK-8527 in Plasma | Predose, 0.25, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, and 168 hours post dose | Blood samples were collected at pre-specified time points to determine the Vz/F of MK-8527 in participant's plasma. Vz/F of MK-8527 in plasma was determined using the formula Dose/(AUC0-inf × λz). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experience One or More Adverse Events (AEs) | Up to approximately 29 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. |
| Number of Participants Who Discontinue Study Due to an AE | Up to approximately 29 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. |
| AUC0-last of MK-8527-triphosphate (TP) in Peripheral Blood Mononuclear Cells (PBMCs) | Predose, 4, 12, 24, 48, 96, 120, 144, 168, 336, 504, 672 hours post dose | Blood samples were collected at pre-specified time points to determine the AUC0-last of MK-8527-TP, the active triphosphate anabolite of MK-8527, in participant's PBMCs. AUC0 to last of MK-8527 was defined as the area under the concentration-time curve from time 0 to the time of the last quantifiable (above lower limit of quantitation) concentration. |
| AUC0-inf of MK-8527-TP in PBMCs | Predose, 4, 12, 24, 48, 96, 120, 144, 168, 336, 504, 672 hours post dose | Blood samples were collected at pre-specified time points to determine the AUC0-inf of MK-8527-TP, the active triphosphate anabolite of MK-8527, in participant's PBMCs. AUC0-inf was defined as AUC0-last + (Cest,last/λz) where Cest,last was the estimated last measurable concentration, and λz was the apparent first-order terminal elimination rate constant. |
| Cmax of MK-8527-TP in PBMCs | Predose, 4, 12, 24, 48, 96, 120, 144, 168, 336, 504, 672 hours post dose | Blood samples were collected at pre-specified time points to determine the Cmax of MK-8527-TP, the active triphosphate anabolite of MK-8527, in participant's PBMCs. Cmax was defined as the maximum observed concentration of MK-8527-TP after the administration of a given dose. |
| Concentration at 168 Hours (C168) of MK-8527-TP in PBMCs | 168 hours post dose | Blood samples were collected at pre-specified time points to determine the C168 of MK-8527-TP, the active triphosphate anabolite of MK-8527, in participant's PBMCs. Geometric mean of C168 of MK-8527-TP in PBMCs was determined. |
| Concentration at 672 Hours (C672) of MK-8527-TP in PBMCs in Participants With Moderate and Severe Renal Impairment | 672 hours post dose | Blood samples were collected at pre-specified time points to determine the C672 of MK-8527-TP, the active triphosphate anabolite of MK-8527, in participant's PBMCs. Geometric mean of C672 of MK-8527-TP in PBMCs was determined. |
| C672 of MK-8527-TP in PBMCs in Healthy Participants | 672 hours post dose | Blood samples were collected at pre-specified time points to determine the C672 of MK-8527-TP, the active triphosphate anabolite of MK-8527, in participant's PBMCs. Since ≤ 50% of healthy participants had BLQ values, the BLQ value was set to zero and the median, minimum, and maximum was reported for C672. |
| Tmax of MK-8527-TP in PBMCs | Predose, 4, 12, 24, 48, 96, 120, 144, 168, 336, 504, 672 hours post dose | Blood samples were collected at pre-specified time points to determine the Tmax of MK-8527-TP, the active triphosphate anabolite of MK-8527, in participant's PBMCs. Tmax of MK-8527-TP was determined by deriving the difference between the time of the blood draw associated with the Cmax and the time of study drug administration |
| T1/2 of MK-8527-TP in PBMCs | Predose, 4, 12, 24, 48, 96, 120, 144, 168, 336, 504, 672 hours post dose | Blood samples were collected at pre-specified time points to determine the t1/2 of MK-8527-TP, the active triphosphate anabolite of MK-8527, in participant's PBMCs. t1/2 was defined as 0.693/Apparent terminal elimination rate constant (λz). |
Countries
United States
Contacts
STUDY_DIRECTORMedical Director
Merck Sharp & Dohme LLC
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 63.8 Years STANDARD_DEVIATION 6.43 |
| Baseline estimated glomerular filtration rate (eGFR) | 100.758 mL/min STANDARD_DEVIATION 9.9802 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 6 Participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 | 0 / 6 |
| other Total, other adverse events | 0 / 6 | 0 / 6 | 0 / 6 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 0 / 6 |
Outcome results
None listed