Renal Impairment
Conditions
Brief summary
The purpose of this study is to compare plasma and urine PK parameters of MK-3866 between participants with impaired renal function and healthy control participants, to investigate the extent to which MK-3866 is removed from the plasma by hemodialysis (HD), and evaluate the safety and tolerability of MK-3866 in participants with impaired renal function.
Detailed description
This is an open-label, 2-part single dose study: Part 1 will include participants with mild, moderate, and severe renal impairment (as well as healthy control participants), and Part 2 will include participants with end stage renal disease (ESRD) undergoing HD. Participants in Part 1 will receive a single IV dose of MK-3866, and plasma and urine samples will be collected over pre-specified time intervals. Participants in Part 2 will receive a single IV dose of MK-3866 on two separate occasions: in Period 1 immediately following their normally-scheduled HD, and in Period 2 approximately 30 minutes prior to their normally-scheduled HD. Plasma, urine, and dialysate samples will be collected over pre-specified time intervals for Part 2.
Interventions
DRUGMK-3866
Single IV infusion of 200 mg administered over 30 minutes (±5 minutes) on Day 1 of each treatment period.
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
* Females of non-childbearing potential. Male participants with female partner(s) of child-bearing potential agree to use a medically acceptable method of contraception during the study and for 90 days after dosing. If partner is pregnant, males agree to use a condom; if partner is of child-bearing potential, partner must use additional birth control * Male participants agree not to donate sperm from the first dose until 90 days after dosing * Adequate venous access Renal Impaired Participants * Liver function tests (serum alanine aminotransferase \[ALT\] and aspartate aminotransferase \[AST\]) and serum bilirubin (total and direct) within upper limit of normal * Panels A, B, and C: no clinically significant change in renal status at least 1 month prior to dosing and not currently or previously been on hemodialysis * Panel E only: ESRD maintained on stable regimen of at least 3 times per week HD for at least 3 months prior to first dosing Healthy Participants * Age within ± 15 years of the mean age of participants with impaired renal function to which the healthy participant is matched * Medically healthy as per medical history, physical examination, vital signs, 12-lead electrocardiograms (ECGs), and clinical laboratory safety tests * Blood urea nitrogen, liver function tests (ALT, AST, alkaline phosphatase \[ALP\]), and serum bilirubin (total and direct) within upper limit of normal.
Exclusion criteria
* Mentally/legally incapacitated, or significant emotional problems or significant psychiatric disorder * History of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological, respiratory, genitourinary or major neurological abnormalities or diseases * History of any illness that might confound the results of the study or poses an additional risk to the participant by their participation in the study * Clinically significant history of cancer * Smoker and/or has used nicotine or nicotine-containing products within 3 months prior to screening * Female participants of childbearing potential, pregnant, or lactating * Positive results for urine or saliva drug screen and/or urine or breath alcohol screen at screening or check-in * Positive results at screening for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV) * Consumes more than 3 glasses of alcoholic beverages within 6 months of screening * Consumes excessive amounts of coffee, tea, cola, energy-drinks, or other caffeinated beverages per day * Major surgery, donated or lost 1 unit of blood within 4 weeks prior to screening, or donated plasma within 7 days prior to dosing in Part 1 or first dose in Part 2 Renal Impaired Participants * Panels A, B, and C: Failed renal transplant or has had nephrectomy * Panels A, B, and C: Rapidly fluctuating renal function, as determined by historical measurements; or demonstrated/suspected renal artery stenosis * Panel E only: Has required frequent emergent HD (≥3) within a year prior to first dosing Healthy Participants * Renal transplant or nephrectomy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Area Under the Plasma Concentration-time Curve of MK-3866 From Time Zero to Infinity (AUC0-inf) | Predose and 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, 12, 24, 36, and 48 hours after dosing on Day 1, and 60 and 72 hours after dosing for Severe Renal Impairment participants | Plasma samples were collected at pre-specified time points and AUC0-inf was assessed. Plasma concentrations of MK-3866 were determined using high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS). |
| Part 1: Area Under the Plasma Concentration-time Curve of MK-3866 From Time Zero to the Time of the Last Quantifiable Sample (AUC0-last) | Predose and 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, 12, 24, 36, and 48 hours after dosing on Day 1, and 60 and 72 hours after dosing for Severe Renal Impairment participants | Plasma samples were collected at pre-specified time points and AUC0-last was assessed. Plasma concentrations of MK-3866 were determined using HPLC-MS/MS. |
| Part 1: Area Under the Plasma Concentration-time Curve of MK-3866 From Time Zero to 24 Hours After Dosing (AUC0-24) | Predose and 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, 12, and 24 hours after dosing on Day 1 | Plasma samples were collected at pre-specified time points and AUC0-24 was assessed. Plasma concentrations of MK-3866 were determined using HPLC-MS/MS. |
| Part 1: Plasma Concentration of MK-3866 at the End of the Infusion (Ceoi) | At the end of the infusion (0.5 hours after infusion start) on Day 1 | Plasma samples were collected at pre-specified time points and Ceoi was assessed. Plasma concentrations of MK-3866 were determined using HPLC-MS/MS. |
| Part 1: Maximum Plasma Concentration of MK-3866 (Cmax) | Predose and 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, 12, 24, 36, and 48 hours after dosing on Day 1, and 60 and 72 hours after dosing for Severe Renal Impairment participants | Plasma samples were collected at pre-specified time points and Cmax was assessed. Plasma concentrations of MK-3866 were determined using HPLC-MS/MS. |
| Part 1: Plasma Clearance of MK-3866 (CL) | Predose and 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, 12, 24, 36, and 48 hours after dosing on Day 1, and 60 and 72 hours after dosing for Severe Renal Impairment participants | Plasma samples were collected at pre-specified time points and CL was assessed. Plasma concentrations of MK-3866 were determined using HPLC-MS/MS. |
| Part 1: Time to Maximum Plasma Concentration of MK-3866 (Tmax) | Predose and 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, 12, 24, 36, and 48 hours after dosing on Day 1, and 60 and 72 hours after dosing for Severe Renal Impairment participants | Plasma samples were collected at pre-specified time points and Tmax was assessed. Plasma concentrations of MK-3866 were determined using HPLC-MS/MS. |
| Part 1: Elimination Terminal Half-life of Plasma MK-3866 (t1/2) | Predose and 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, 12, 24, 36, and 48 hours after dosing on Day 1, and 60 and 72 hours after dosing for Severe Renal Impairment participants | Plasma samples were collected at pre-specified time points and t1/2 was assessed. Plasma concentrations of MK-3866 were determined using HPLC-MS/MS. Method of dispersion used for these data is geometric % coefficient of variation (%CV). |
| Part 1: Volume of Distribution of Plasma MK-3866 (Vz) | Predose and 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, 12, 24, 36, and 48 hours after dosing on Day 1, and 60 and 72 hours after dosing for Severe Renal Impairment participants | Plasma samples were collected at pre-specified time points and Vz was assessed. Plasma concentrations of MK-3866 were determined using HPLC-MS/MS. Method of dispersion used for these data is geometric %CV. |
| Part 2: AUC0-inf of Plasma MK-3866 | Predose and 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, 12, 24, 36, 48, 60, and 72 hours after dosing on Day 1 of Period 1 and 2, and 2.5, 3.5, and 4 hours after dosing on Day 1 of Period 2 | Plasma samples were collected at pre-specified time points and AUC0-inf was assessed. Plasma concentrations of MK-3866 were determined using HPLC-MS/MS. For ESRD participants, hemodialysis took place predose in Period 1 and from 0.5 to 4.5 hours after dosing in Period 2. Data for healthy participants are from Part 1. |
| Part 2: AUC0-last of Plasma MK-3866 | Predose and 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, 12, 24, 36, 48, 60, and 72 hours after dosing on Day 1 of Period 1 and 2, and 2.5, 3.5, and 4 hours after dosing on Day 1 of Period 2 | Plasma samples were collected at pre-specified time points and AUC0-last was assessed. Plasma concentrations of MK-3866 were determined using HPLC-MS/MS. For ESRD participants, hemodialysis took place predose in Period 1 and from 0.5 to 4.5 hours after dosing in Period 2. Data for healthy participants are from Part 1. |
| Part 2: AUC0-24 of Plasma MK-3866 | Predose and 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, 12, and 24 hours after dosing on Day 1 of Period 1 and 2, and 2.5, 3.5, and 4 hours after dosing on Day 1 of Period 2 | Plasma samples were collected at pre-specified time points and AUC0-24 was assessed. Plasma concentrations of MK-3866 were determined using HPLC-MS/MS. For ESRD participants, hemodialysis took place predose in Period 1 and from 0.5 to 4.5 hours after dosing in Period 2. Data for healthy participants are from Part 1. |
| Part 2: Ceoi of Plasma MK-3866 | At the end of the infusion (0.5 hours after infusion start) on Day 1 of Period 1 and Period 2 | Plasma samples were collected at pre-specified time points and Ceoi was assessed. Plasma concentrations of MK-3866 were determined using HPLC-MS/MS. For ESRD participants, hemodialysis took place predose in Period 1 and from 0.5 to 4.5 hours after dosing in Period 2. Data for healthy participants are from Part 1. |
| Part 2: Cmax of Plasma MK-3866 | Predose and 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, 12, 24, 36, 48, 60, and 72 hours after dosing on Day 1 of Period 1 and 2, and 2.5, 3.5, and 4 hours after dosing on Day 1 of Period 2 | Plasma samples were collected at pre-specified time points and Cmax was assessed. Plasma concentrations of MK-3866 were determined using HPLC-MS/MS. For ESRD participants, hemodialysis took place predose in Period 1 and from 0.5 to 4.5 hours after dosing in Period 2. Data for healthy participants are from Part 1. |
| Part 2: CL of Plasma MK-3866 | Predose and 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, 12, 24, 36, 48, 60, and 72 hours after dosing on Day 1 of Period 1 and 2, and 2.5, 3.5, and 4 hours after dosing on Day 1 of Period 2 | Plasma samples were collected at pre-specified time points and CL was assessed. Plasma concentrations of MK-3866 were determined using HPLC-MS/MS. For ESRD participants, hemodialysis took place predose in Period 1 and from 0.5 to 4.5 hours after dosing in Period 2. Data for healthy participants are from Part 1. |
| Part 2: Tmax of Plasma MK-3866 | Predose and 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, 12, 24, 36, 48, 60, and 72 hours after dosing on Day 1 of Period 1 and 2, and 2.5, 3.5, and 4 hours after dosing on Day 1 of Period 2 | Plasma samples were collected at pre-specified time points and Tmax was assessed. Plasma concentrations of MK-3866 were determined using HPLC-MS/MS. For ESRD participants, hemodialysis took place predose in Period 1 and from 0.5 to 4.5 hours after dosing in Period 2. Data for healthy participants are from Part 1. |
| Part 2: t1/2 of Plasma MK-3866 | Predose and 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, 12, 24, 36, 48, 60, and 72 hours after dosing on Day 1 of Period 1 and 2, and 2.5, 3.5, and 4 hours after dosing on Day 1 of Period 2 | Plasma samples were collected at pre-specified time points and t1/2 was assessed. Plasma concentrations of MK-3866 were determined using HPLC-MS/MS. For ESRD participants, hemodialysis took place predose in Period 1 and from 0.5 to 4.5 hours after dosing in Period 2. Data for healthy participants are from Part 1. Method of dispersion used for these data is geometric %CV. |
| Part 2: Vz of Plasma MK-3866 | Predose and 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, 12, 24, 36, 48, 60, and 72 hours after dosing on Day 1 of Period 1 and 2, and 2.5, 3.5, and 4 hours after dosing on Day 1 of Period 2 | Plasma samples were collected at pre-specified time points and Vz was assessed. Plasma concentrations of MK-3866 were determined using HPLC-MS/MS. For ESRD participants, hemodialysis took place predose in Period 1 and from 0.5 to 4.5 hours after dosing in Period 2. Data for healthy participants are from Part 1. Method of dispersion used for these data is geometric %CV. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Total Amount of MK-3866 Excreted in the Urine Over 24 Hours (Ae0-24) | Predose and 0-4, 4-8, 8-12, and 12-24 hours after dosing on Day 1 | Urine samples were collected at pre-specified intervals and Ae0-24 was assessed. Ae0-24 was obtained by adding the amounts excreted over each collection interval. Urine concentrations of MK-3866 were determined using HPLC-MS/MS. |
| Number of Participants Discontinuing the Study Due to an Adverse Event | Part 1: up to Day 14 after dosing; Part 2, Period 1: up to Day 14 after dosing (including ≥6 day washout period); Part 2, Period 2: up to Day 14 after dosing | An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. |
| Part 1: Renal Clearance (CLr) of MK-3866 | Predose and 0-4, 4-8, 8-12, and 12-24 hours after dosing on Day 1 | Urine samples were collected at pre-specified intervals and CLr was assessed. CLr was calculated as AE(t'-t)/AUC(t'-t), where t'-t is the longest interval of time during which AE and AUC are both obtained. Urine concentrations of MK-3866 were determined using HPLC-MS/MS. |
| Part 1: Fraction of MK-3866 Excretion (Urine) During Each Collection Interval (Fe0-24) | Predose and 0-4, 4-8, 8-12, and 12-24 hours after dosing on Day 1 | Urine samples were collected at pre-specified intervals and Fe0-24 was assessed. Fe0-24 was obtained by dividing the amount of MK-3866 excreted in each collection interval by the dose. Urine concentrations of MK-3866 were determined using HPLC-MS/MS. |
| Part 2: Total Amount of MK-3866 Excreted Unchanged in the Urine Over the Period of 24 Hours (Ae0-24) | Predose and 0-4, 4-8, 8-12, and 12-24 hours after dosing on Day 1 of Period 1 and Period 2 | Urine samples were collected at pre-specified intervals and Ae0-24 was assessed. Ae0-24 was obtained by adding the amounts excreted over each collection interval. Urine concentrations of MK-3866 were determined using HPLC-MS/MS. Method of dispersion used for these data is geometric %CV. |
| Part 2: Renal Clearance (CLr) of MK-3866 | Predose and 0-4, 4-8, 8-12, and 12-24 hours after dosing on Day 1 of Period 1 and Period 2 | Urine samples were collected at pre-specified intervals and CLr was assessed. CLr was calculated as AE(t'-t)/AUC(t'-t), where t'-t is the longest interval of time during which AE and AUC are both obtained. Urine concentrations of MK-3866 were determined using HPLC-MS/MS. Method of dispersion used for these data is geometric %CV. |
| Part 2: Fraction of MK-3866 Excretion (Urine) During Each Collection Interval (Fe0-24) | Predose and 0-4, 4-8, 8-12, and 12-24 hours after dosing on Day 1 of Period 1 and Period 2 | Urine samples were collected at pre-specified intervals and Fe0-24 was assessed. Fe0-24 was obtained by dividing the amount of MK-3866 excreted in each collection interval by the dose. Urine concentrations of MK-3866 were determined using HPLC-MS/MS. Method of dispersion used for these data is geometric %CV. |
| Part 2: Concentration of MK-3866 in Plasma Entering the Dialyzer Line (Ca) | 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, and 4.5 hours after dosing on Day 1 of Period 2 | Plasma samples entering the dialyzer line were collected at pre-specified time points and Ca was assessed. Concentrations of MK-3866 were determined using HPLC-MS/MS. Method of dispersion used for these data is geometric %CV. |
| Part 2: Concentration of MK-3866 in Plasma Exiting the Dialyzer Line (Cv) | 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, and 4.5 hours after dosing on Day 1 of Period 2 | Plasma samples exiting the dialyzer line were collected at pre-specified time points and Cv was assessed. Concentrations of MK-3866 were determined using HPLC-MS/MS. Method of dispersion used for these data is geometric %CV. |
| Part 2: Area Under the Concentration-time Curve of MK-3866 in Plasma Entering the Dialyzer Line During the Dialysis Period (AUCD) | 0.5 (beginning of HD), 1, 1.5, 2, 2.5, 3, 3.5, 4, and 4.5 hours after dosing on Day 1 of Period 2 | Plasma samples entering the dialyzer line were collected at pre-specified time points and AUCD was assessed. AUCD values were determined from the Ca versus time profile during the HD period, using the 'linear up, log down' calculation method. Concentrations of MK-3866 were determined using HPLC-MS/MS. Method of dispersion used for these data is geometric %CV. |
| Part 2: Area Under the Concentration-time Curve of MK-3866 in Plasma Entering the Dialyzer Line From 0.75 to 4.5 Hours During the Dialysis Period (AUC[0.75-4.5]Ca) | 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, and 4.5 hours after dosing on Day 1 of Period 2 | Plasma samples entering the dialyzer line were collected at pre-specified time points and AUC\[0.75-4.5\]Ca was assessed. AUC\[0.75-4.5\]Ca values were determined from the Ca versus time profile from 0.75 to 4.5 hours during the HD period, using the 'linear up, log down' calculation method. Concentrations of MK-3866 were determined using HPLC-MS/MS. Method of dispersion used for these data is geometric %CV. |
| Part 2: Area Under the Concentration-time Curve of MK-3866 in Plasma Entering the Dialyzer Line From 0.75 to 4.5 Hours During the Dialysis Period (AUC[0.75-4.5]Cv) | 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, and 4.5 hours after dosing on Day 1 of Period 2 | Plasma samples entering the dialyzer line were collected at pre-specified time points and AUC\[0.75-4.5\]Cv was assessed. AUC\[0.75-4.5\]Cv values were determined from the Cv versus time profile from 0.75 to 4.5 hours during the HD period, using the 'linear up, log down' calculation method. Concentrations of MK-3866 were determined using HPLC-MS/MS. Method of dispersion used for these data is geometric %CV. |
| Part 2: Dialysis Clearance of MK-3866 Based on Plasma (CLD,Plasma) | 0.5 (beginning of HD), 1, 1.5, 2, 2.5, 3, 3.5, 4, and 4.5 hours after dosing on Day 1 of Period 2 | Plasma dialysis samples were collected at pre-specified time points and CLD was assessed. CLD was calculated as Q x R x (AUC\[1-4.5\]Ca - AUC\[1-4.5\]Cv) / AUC\[1-4.5\]Ca, where Q is the flow rate of blood through the dialyzer, and R is the ratio of blood drug concentration to plasma drug concentration. Concentrations of MK-3866 were determined using HPLC-MS/MS. Method of dispersion used for these data is geometric %CV. |
| Part 2: Concentration of MK-3866 in Dialysate Samples (CD) | 0.5 (beginning of HD), 1, 1.5, 2, 2.5, 3, 3.5, 4, and 4.5 hours after dosing on Day 1 of Period 2 | Plasma dialysis samples were collected at pre-specified time points and CD was assessed. Concentrations of MK-3866 were determined using HPLC-MS/MS. |
| Part 2: Amount of MK-3866 Recovered From Each Dialysate Sample (AD) | 0.5 (beginning of HD), 1, 1.5, 2, 2.5, 3, 3.5, 4, and 4.5 hours after dosing on Day 1 of Period 2 | Plasma dialysis samples were collected at pre-specified time points and AD was assessed. Concentrations of MK-3866 were determined using HPLC-MS/MS. Method of dispersion used for these data is geometric %CV. |
| Part 2: Rate of Removal of MK-3866 From the Dialysate (rr) | 0.5 (beginning of HD), 1, 1.5, 2, 2.5, 3, 3.5, 4, and 4.5 hours after dosing on Day 1 of Period 2 | Plasma dialysis samples were collected at pre-specified time points and rr was assessed. rr was calculated as CD x dialysate flow rate. Concentrations of MK-3866 were determined using HPLC-MS/MS. Method of dispersion used for these data is geometric %CV. |
| Part 2: Cumulative Amount of MK-3866 Recovered From the Dialysate (AD,Total) | 0.5 (beginning of HD), 1, 1.5, 2, 2.5, 3, 3.5, 4, and 4.5 hours after dosing on Day 1 of Period 2 | Plasma dialysis samples were collected at pre-specified time points and AD,total was assessed. AD,total was obtained by integrating the rr versus time profile over the dialysis session duration, using actual times relative to the start time of dialysis. Concentrations of MK-3866 were determined using HPLC-MS/MS. Method of dispersion used for these data is geometric %CV. |
| Part 2: Hemodialysis Clearance of MK-3866 Based on the Dialysate(CLD,Dialysate) | 0.5 (beginning of HD), 1, 1.5, 2, 2.5, 3, 3.5, 4, and 4.5 hours after dosing on Day 1 of Period 2 | Plasma dialysis samples were collected at pre-specified time points and CLD,dialysate was assessed. CLD,dialysate was calculated as AD.total / AUCD. Concentrations of MK-3866 were determined using HPLC-MS/MS. Method of dispersion used for these data is geometric %CV. |
| Number of Participants With at Least One Adverse Event (AE) | Part 1: up to Day 14 after dosing; Part 2, Period 1: up to Day 14 after dosing (including ≥6 day washout period); Part 2, Period 2: up to Day 14 after dosing | An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Part 1: Mild Renal Impairment (RI) Participants received a single intravenous (IV) infusion of MK-3886 200 mg over 30 minutes on Day 1. | 8 |
| Part 1: Moderate Renal Impairment Participants received a single IV infusion of MK-3886 200 mg over 30 minutes on Day 1. | 8 |
| Part 1: Severe Renal Impairment Participants received a single IV infusion of MK-3886 200 mg over 30 minutes on Day 1. | 8 |
| Part 1: Healthy Participants Participants received a single IV infusion of MK-3886 200 mg over 30 minutes on Day 1. | 10 |
| Part 2: End-stage Renal Disease Undergoing Hemodialysis End-stage renal disease (ESRD) participants received a single IV infusion of MK-3886 200 mg over 30 minutes on Day 1 just after hemodialysis (HD) in Period 1 and just before HD in Period 2. There was a washout of at least 6 days before dosing in Period 2. | 8 |
| Total | 42 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Part 1 and Period 1 of Part 2 | Adverse Event | 0 | 0 | 0 | 0 | 1 |
| Period 2 of Part 2 | Adverse Event | 0 | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Part 1: Mild Renal Impairment (RI) | Part 1: Moderate Renal Impairment | Part 1: Severe Renal Impairment | Part 1: Healthy Participants | Part 2: End-stage Renal Disease Undergoing Hemodialysis | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 68.3 Years STANDARD_DEVIATION 5.65 | 67.0 Years STANDARD_DEVIATION 9.24 | 57.3 Years STANDARD_DEVIATION 13.83 | 61.2 Years STANDARD_DEVIATION 8.36 | 51.9 Years STANDARD_DEVIATION 8.68 | 61.1 Years STANDARD_DEVIATION 10.83 |
| Body Mass Index | 28.125 kg/m^2 | 27.625 kg/m^2 | 28.625 kg/m^2 | 28.800 kg/m^2 | 29.875 kg/m^2 | 28.619 kg/m^2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 4 Participants | 4 Participants | 4 Participants | 1 Participants | 15 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 4 Participants | 4 Participants | 6 Participants | 7 Participants | 27 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 1 Participants | 3 Participants | 2 Participants | 7 Participants | 15 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 6 Participants | 5 Participants | 8 Participants | 1 Participants | 26 Participants |
| Sex: Female, Male Female | 4 Participants | 2 Participants | 2 Participants | 4 Participants | 3 Participants | 15 Participants |
| Sex: Female, Male Male | 4 Participants | 6 Participants | 6 Participants | 6 Participants | 5 Participants | 27 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 7 | 0 / 10 |
| other Total, other adverse events | 3 / 8 | 3 / 8 | 1 / 8 | 0 / 8 | 0 / 7 | 1 / 10 |
| serious Total, serious adverse events | 0 / 8 | 0 / 8 | 0 / 8 | 1 / 8 | 1 / 7 | 0 / 10 |
Outcome results
Primary
Part 1: Area Under the Plasma Concentration-time Curve of MK-3866 From Time Zero to 24 Hours After Dosing (AUC0-24)
Plasma samples were collected at pre-specified time points and AUC0-24 was assessed. Plasma concentrations of MK-3866 were determined using HPLC-MS/MS.
Time frame: Predose and 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, 12, and 24 hours after dosing on Day 1
Population: All participants who received MK-3866 infusion. Healthy participants were those who matched gender, and mean age and BMI of the comparator experimental group(s).
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| Part 1: Mild Renal Impairment (RI) | Part 1: Area Under the Plasma Concentration-time Curve of MK-3866 From Time Zero to 24 Hours After Dosing (AUC0-24) | 96.2 µM*hr |
| Part 1: Moderate Renal Impairment | Part 1: Area Under the Plasma Concentration-time Curve of MK-3866 From Time Zero to 24 Hours After Dosing (AUC0-24) | 127 µM*hr |
| Part 1: Healthy Participants (Mild + Moderate RI) | Part 1: Area Under the Plasma Concentration-time Curve of MK-3866 From Time Zero to 24 Hours After Dosing (AUC0-24) | 79.7 µM*hr |
| Part 1: Severe Renal Impairment | Part 1: Area Under the Plasma Concentration-time Curve of MK-3866 From Time Zero to 24 Hours After Dosing (AUC0-24) | 182 µM*hr |
| Part 1: Healthy Participants (Severe RI) | Part 1: Area Under the Plasma Concentration-time Curve of MK-3866 From Time Zero to 24 Hours After Dosing (AUC0-24) | 78.1 µM*hr |
90% CI: [1.04, 1.4]
90% CI: [1.36, 1.86]
90% CI: [1.82, 2.97]
Primary
Part 1: Area Under the Plasma Concentration-time Curve of MK-3866 From Time Zero to Infinity (AUC0-inf)
Plasma samples were collected at pre-specified time points and AUC0-inf was assessed. Plasma concentrations of MK-3866 were determined using high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS).
Time frame: Predose and 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, 12, 24, 36, and 48 hours after dosing on Day 1, and 60 and 72 hours after dosing for Severe Renal Impairment participants
Population: All participants who received MK-3866 infusion. Healthy participants were those who matched gender, and mean age and BMI of the comparator experimental group(s).
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| Part 1: Mild Renal Impairment (RI) | Part 1: Area Under the Plasma Concentration-time Curve of MK-3866 From Time Zero to Infinity (AUC0-inf) | 104 µM*hr |
| Part 1: Moderate Renal Impairment | Part 1: Area Under the Plasma Concentration-time Curve of MK-3866 From Time Zero to Infinity (AUC0-inf) | 141 µM*hr |
| Part 1: Healthy Participants (Mild + Moderate RI) | Part 1: Area Under the Plasma Concentration-time Curve of MK-3866 From Time Zero to Infinity (AUC0-inf) | 83.5 µM*hr |
| Part 1: Severe Renal Impairment | Part 1: Area Under the Plasma Concentration-time Curve of MK-3866 From Time Zero to Infinity (AUC0-inf) | 244 µM*hr |
| Part 1: Healthy Participants (Severe RI) | Part 1: Area Under the Plasma Concentration-time Curve of MK-3866 From Time Zero to Infinity (AUC0-inf) | 81.8 µM*hr |
90% CI: [1.07, 1.47]
90% CI: [1.42, 2.02]
90% CI: [2.2, 4.04]
Primary
Part 1: Area Under the Plasma Concentration-time Curve of MK-3866 From Time Zero to the Time of the Last Quantifiable Sample (AUC0-last)
Plasma samples were collected at pre-specified time points and AUC0-last was assessed. Plasma concentrations of MK-3866 were determined using HPLC-MS/MS.
Time frame: Predose and 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, 12, 24, 36, and 48 hours after dosing on Day 1, and 60 and 72 hours after dosing for Severe Renal Impairment participants
Population: All participants who received MK-3866 infusion. Healthy participants were those who matched gender, and mean age and BMI of the comparator experimental group(s).
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| Part 1: Mild Renal Impairment (RI) | Part 1: Area Under the Plasma Concentration-time Curve of MK-3866 From Time Zero to the Time of the Last Quantifiable Sample (AUC0-last) | 103 µM*hr |
| Part 1: Moderate Renal Impairment | Part 1: Area Under the Plasma Concentration-time Curve of MK-3866 From Time Zero to the Time of the Last Quantifiable Sample (AUC0-last) | 139 µM*hr |
| Part 1: Healthy Participants (Mild + Moderate RI) | Part 1: Area Under the Plasma Concentration-time Curve of MK-3866 From Time Zero to the Time of the Last Quantifiable Sample (AUC0-last) | 83.0 µM*hr |
| Part 1: Severe Renal Impairment | Part 1: Area Under the Plasma Concentration-time Curve of MK-3866 From Time Zero to the Time of the Last Quantifiable Sample (AUC0-last) | 237 µM*hr |
| Part 1: Healthy Participants (Severe RI) | Part 1: Area Under the Plasma Concentration-time Curve of MK-3866 From Time Zero to the Time of the Last Quantifiable Sample (AUC0-last) | 81.4 µM*hr |
90% CI: [1.06, 1.46]
90% CI: [1.41, 1.99]
90% CI: [2.17, 3.9]
Primary
Part 1: Elimination Terminal Half-life of Plasma MK-3866 (t1/2)
Plasma samples were collected at pre-specified time points and t1/2 was assessed. Plasma concentrations of MK-3866 were determined using HPLC-MS/MS. Method of dispersion used for these data is geometric % coefficient of variation (%CV).
Time frame: Predose and 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, 12, 24, 36, and 48 hours after dosing on Day 1, and 60 and 72 hours after dosing for Severe Renal Impairment participants
Population: All participants who received MK-3866 infusion. Healthy participants were those who matched gender, and mean age and BMI of the comparator experimental group(s).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Mild Renal Impairment (RI) | Part 1: Elimination Terminal Half-life of Plasma MK-3866 (t1/2) | 7.38 Hours | Geometric Coefficient of Variation 13.3 |
| Part 1: Moderate Renal Impairment | Part 1: Elimination Terminal Half-life of Plasma MK-3866 (t1/2) | 8.23 Hours | Geometric Coefficient of Variation 17 |
| Part 1: Healthy Participants (Mild + Moderate RI) | Part 1: Elimination Terminal Half-life of Plasma MK-3866 (t1/2) | 7.00 Hours | Geometric Coefficient of Variation 12.7 |
| Part 1: Severe Renal Impairment | Part 1: Elimination Terminal Half-life of Plasma MK-3866 (t1/2) | 14.7 Hours | Geometric Coefficient of Variation 17.8 |
| Part 1: Healthy Participants (Severe RI) | Part 1: Elimination Terminal Half-life of Plasma MK-3866 (t1/2) | 6.90 Hours | Geometric Coefficient of Variation 13 |
Primary
Part 1: Maximum Plasma Concentration of MK-3866 (Cmax)
Plasma samples were collected at pre-specified time points and Cmax was assessed. Plasma concentrations of MK-3866 were determined using HPLC-MS/MS.
Time frame: Predose and 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, 12, 24, 36, and 48 hours after dosing on Day 1, and 60 and 72 hours after dosing for Severe Renal Impairment participants
Population: All participants who received MK-3866 infusion. Healthy participants were those who matched gender, and mean age and BMI of the combined comparator experimental groups.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Part 1: Mild Renal Impairment (RI) | Part 1: Maximum Plasma Concentration of MK-3866 (Cmax) | 27.4 µM |
| Part 1: Moderate Renal Impairment | Part 1: Maximum Plasma Concentration of MK-3866 (Cmax) | 28.0 µM |
| Part 1: Healthy Participants (Mild + Moderate RI) | Part 1: Maximum Plasma Concentration of MK-3866 (Cmax) | 28.7 µM |
| Part 1: Severe Renal Impairment | Part 1: Maximum Plasma Concentration of MK-3866 (Cmax) | 26.7 µM |
Primary
Part 1: Plasma Clearance of MK-3866 (CL)
Plasma samples were collected at pre-specified time points and CL was assessed. Plasma concentrations of MK-3866 were determined using HPLC-MS/MS.
Time frame: Predose and 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, 12, 24, 36, and 48 hours after dosing on Day 1, and 60 and 72 hours after dosing for Severe Renal Impairment participants
Population: All participants who received MK-3866 infusion. Healthy participants were those who matched gender, and mean age and BMI of the comparator experimental group(s).
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| Part 1: Mild Renal Impairment (RI) | Part 1: Plasma Clearance of MK-3866 (CL) | 3.80 L/hr |
| Part 1: Moderate Renal Impairment | Part 1: Plasma Clearance of MK-3866 (CL) | 2.80 L/hr |
| Part 1: Healthy Participants (Mild + Moderate RI) | Part 1: Plasma Clearance of MK-3866 (CL) | 4.75 L/hr |
| Part 1: Severe Renal Impairment | Part 1: Plasma Clearance of MK-3866 (CL) | 1.62 L/hr |
| Part 1: Healthy Participants (Severe RI) | Part 1: Plasma Clearance of MK-3866 (CL) | 4.85 L/hr |
90% CI: [0.68, 0.94]
90% CI: [0.49, 0.7]
90% CI: [0.25, 0.45]
Primary
Part 1: Plasma Concentration of MK-3866 at the End of the Infusion (Ceoi)
Plasma samples were collected at pre-specified time points and Ceoi was assessed. Plasma concentrations of MK-3866 were determined using HPLC-MS/MS.
Time frame: At the end of the infusion (0.5 hours after infusion start) on Day 1
Population: All participants who received MK-3866 infusion. Healthy participants were those who matched gender, and mean age and BMI of the comparator experimental group(s).
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| Part 1: Mild Renal Impairment (RI) | Part 1: Plasma Concentration of MK-3866 at the End of the Infusion (Ceoi) | 26.6 µM |
| Part 1: Moderate Renal Impairment | Part 1: Plasma Concentration of MK-3866 at the End of the Infusion (Ceoi) | 27.7 µM |
| Part 1: Healthy Participants (Mild + Moderate RI) | Part 1: Plasma Concentration of MK-3866 at the End of the Infusion (Ceoi) | 27.0 µM |
| Part 1: Severe Renal Impairment | Part 1: Plasma Concentration of MK-3866 at the End of the Infusion (Ceoi) | 29.7 µM |
| Part 1: Healthy Participants (Severe RI) | Part 1: Plasma Concentration of MK-3866 at the End of the Infusion (Ceoi) | 26.9 µM |
90% CI: [0.84, 1.16]
90% CI: [0.9, 1.18]
90% CI: [0.95, 1.29]
Primary
Part 1: Time to Maximum Plasma Concentration of MK-3866 (Tmax)
Plasma samples were collected at pre-specified time points and Tmax was assessed. Plasma concentrations of MK-3866 were determined using HPLC-MS/MS.
Time frame: Predose and 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, 12, 24, 36, and 48 hours after dosing on Day 1, and 60 and 72 hours after dosing for Severe Renal Impairment participants
Population: All participants who received MK-3866 infusion. Healthy participants were those who matched gender, and mean age and BMI of the comparator experimental group(s).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: Mild Renal Impairment (RI) | Part 1: Time to Maximum Plasma Concentration of MK-3866 (Tmax) | 0.50 Hours |
| Part 1: Moderate Renal Impairment | Part 1: Time to Maximum Plasma Concentration of MK-3866 (Tmax) | 0.49 Hours |
| Part 1: Healthy Participants (Mild + Moderate RI) | Part 1: Time to Maximum Plasma Concentration of MK-3866 (Tmax) | 0.50 Hours |
| Part 1: Severe Renal Impairment | Part 1: Time to Maximum Plasma Concentration of MK-3866 (Tmax) | 0.50 Hours |
| Part 1: Healthy Participants (Severe RI) | Part 1: Time to Maximum Plasma Concentration of MK-3866 (Tmax) | 0.50 Hours |
Primary
Part 1: Volume of Distribution of Plasma MK-3866 (Vz)
Plasma samples were collected at pre-specified time points and Vz was assessed. Plasma concentrations of MK-3866 were determined using HPLC-MS/MS. Method of dispersion used for these data is geometric %CV.
Time frame: Predose and 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, 12, 24, 36, and 48 hours after dosing on Day 1, and 60 and 72 hours after dosing for Severe Renal Impairment participants
Population: All participants who received MK-3866 infusion. Healthy participants were those who matched gender, and mean age and BMI of the comparator experimental group(s).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Mild Renal Impairment (RI) | Part 1: Volume of Distribution of Plasma MK-3866 (Vz) | 40.4 Liters | Geometric Coefficient of Variation 18.3 |
| Part 1: Moderate Renal Impairment | Part 1: Volume of Distribution of Plasma MK-3866 (Vz) | 33.3 Liters | Geometric Coefficient of Variation 18 |
| Part 1: Healthy Participants (Mild + Moderate RI) | Part 1: Volume of Distribution of Plasma MK-3866 (Vz) | 48.0 Liters | Geometric Coefficient of Variation 17.3 |
| Part 1: Severe Renal Impairment | Part 1: Volume of Distribution of Plasma MK-3866 (Vz) | 34.4 Liters | Geometric Coefficient of Variation 29.5 |
| Part 1: Healthy Participants (Severe RI) | Part 1: Volume of Distribution of Plasma MK-3866 (Vz) | 48.3 Liters | Geometric Coefficient of Variation 17.7 |
Primary
Part 2: AUC0-24 of Plasma MK-3866
Plasma samples were collected at pre-specified time points and AUC0-24 was assessed. Plasma concentrations of MK-3866 were determined using HPLC-MS/MS. For ESRD participants, hemodialysis took place predose in Period 1 and from 0.5 to 4.5 hours after dosing in Period 2. Data for healthy participants are from Part 1.
Time frame: Predose and 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, 12, and 24 hours after dosing on Day 1 of Period 1 and 2, and 2.5, 3.5, and 4 hours after dosing on Day 1 of Period 2
Population: All participants who received MK-3866 infusion. Healthy participants were those who matched gender, and mean age and BMI of the comparator experimental group(s).
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| Part 1: Mild Renal Impairment (RI) | Part 2: AUC0-24 of Plasma MK-3866 | 203 µM*hr |
| Part 1: Moderate Renal Impairment | Part 2: AUC0-24 of Plasma MK-3866 | 84.7 µM*hr |
| Part 1: Healthy Participants (Mild + Moderate RI) | Part 2: AUC0-24 of Plasma MK-3866 | 77.8 µM*hr |
90% CI: [2.23, 3.06]
90% CI: [0.95, 1.25]
Primary
Part 2: AUC0-inf of Plasma MK-3866
Plasma samples were collected at pre-specified time points and AUC0-inf was assessed. Plasma concentrations of MK-3866 were determined using HPLC-MS/MS. For ESRD participants, hemodialysis took place predose in Period 1 and from 0.5 to 4.5 hours after dosing in Period 2. Data for healthy participants are from Part 1.
Time frame: Predose and 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, 12, 24, 36, 48, 60, and 72 hours after dosing on Day 1 of Period 1 and 2, and 2.5, 3.5, and 4 hours after dosing on Day 1 of Period 2
Population: All participants who received MK-3866 infusion. Healthy participants were those who matched gender, and mean age and BMI of the comparator experimental group(s).
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| Part 1: Mild Renal Impairment (RI) | Part 2: AUC0-inf of Plasma MK-3866 | 323 µM*hr |
| Part 1: Moderate Renal Impairment | Part 2: AUC0-inf of Plasma MK-3866 | 129 µM*hr |
| Part 1: Healthy Participants (Mild + Moderate RI) | Part 2: AUC0-inf of Plasma MK-3866 | 81.3 µM*hr |
90% CI: [3.26, 4.82]
90% CI: [1.3, 1.92]
Primary
Part 2: AUC0-last of Plasma MK-3866
Plasma samples were collected at pre-specified time points and AUC0-last was assessed. Plasma concentrations of MK-3866 were determined using HPLC-MS/MS. For ESRD participants, hemodialysis took place predose in Period 1 and from 0.5 to 4.5 hours after dosing in Period 2. Data for healthy participants are from Part 1.
Time frame: Predose and 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, 12, 24, 36, 48, 60, and 72 hours after dosing on Day 1 of Period 1 and 2, and 2.5, 3.5, and 4 hours after dosing on Day 1 of Period 2
Population: All participants who received MK-3866 infusion. Healthy participants were those who matched gender, and mean age and BMI of the comparator experimental group(s).
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| Part 1: Mild Renal Impairment (RI) | Part 2: AUC0-last of Plasma MK-3866 | 294 µM*hr |
| Part 1: Moderate Renal Impairment | Part 2: AUC0-last of Plasma MK-3866 | 118 µM*hr |
| Part 1: Healthy Participants (Mild + Moderate RI) | Part 2: AUC0-last of Plasma MK-3866 | 80.9 µM*hr |
90% CI: [3.03, 4.36]
90% CI: [1.22, 1.75]
Primary
Part 2: Ceoi of Plasma MK-3866
Plasma samples were collected at pre-specified time points and Ceoi was assessed. Plasma concentrations of MK-3866 were determined using HPLC-MS/MS. For ESRD participants, hemodialysis took place predose in Period 1 and from 0.5 to 4.5 hours after dosing in Period 2. Data for healthy participants are from Part 1.
Time frame: At the end of the infusion (0.5 hours after infusion start) on Day 1 of Period 1 and Period 2
Population: All participants who received MK-3866 infusion. Healthy participants were those who matched gender, and mean age and BMI of the comparator experimental group(s).
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| Part 1: Mild Renal Impairment (RI) | Part 2: Ceoi of Plasma MK-3866 | 26.3 µM |
| Part 1: Moderate Renal Impairment | Part 2: Ceoi of Plasma MK-3866 | 25.3 µM |
| Part 1: Healthy Participants (Mild + Moderate RI) | Part 2: Ceoi of Plasma MK-3866 | 26.8 µM |
90% CI: [0.84, 1.14]
90% CI: [0.75, 1.2]
Primary
Part 2: CL of Plasma MK-3866
Plasma samples were collected at pre-specified time points and CL was assessed. Plasma concentrations of MK-3866 were determined using HPLC-MS/MS. For ESRD participants, hemodialysis took place predose in Period 1 and from 0.5 to 4.5 hours after dosing in Period 2. Data for healthy participants are from Part 1.
Time frame: Predose and 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, 12, 24, 36, 48, 60, and 72 hours after dosing on Day 1 of Period 1 and 2, and 2.5, 3.5, and 4 hours after dosing on Day 1 of Period 2
Population: All participants who received MK-3866 infusion. Healthy participants were those who matched gender, and mean age and BMI of the comparator experimental group(s).
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Part 1: Mild Renal Impairment (RI) | Part 2: CL of Plasma MK-3866 | 1.23 L/hr |
| Part 1: Moderate Renal Impairment | Part 2: CL of Plasma MK-3866 | 3.08 L/hr |
| Part 1: Healthy Participants (Mild + Moderate RI) | Part 2: CL of Plasma MK-3866 | 4.87 L/hr |
90% CI: [0.21, 0.31]
95% CI: [0.52, 0.77]
Primary
Part 2: Cmax of Plasma MK-3866
Plasma samples were collected at pre-specified time points and Cmax was assessed. Plasma concentrations of MK-3866 were determined using HPLC-MS/MS. For ESRD participants, hemodialysis took place predose in Period 1 and from 0.5 to 4.5 hours after dosing in Period 2. Data for healthy participants are from Part 1.
Time frame: Predose and 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, 12, 24, 36, 48, 60, and 72 hours after dosing on Day 1 of Period 1 and 2, and 2.5, 3.5, and 4 hours after dosing on Day 1 of Period 2
Population: All participants who received MK-3866 infusion. Healthy participants were those who matched gender, and mean age and BMI of the comparator experimental group(s).
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| Part 1: Mild Renal Impairment (RI) | Part 2: Cmax of Plasma MK-3866 | 26.6 µM |
| Part 1: Moderate Renal Impairment | Part 2: Cmax of Plasma MK-3866 | 25.3 µM |
| Part 1: Healthy Participants (Mild + Moderate RI) | Part 2: Cmax of Plasma MK-3866 | 26.8 µM |
90% CI: [0.85, 1.16]
90% CI: [0.75, 1.2]
Primary
Part 2: t1/2 of Plasma MK-3866
Plasma samples were collected at pre-specified time points and t1/2 was assessed. Plasma concentrations of MK-3866 were determined using HPLC-MS/MS. For ESRD participants, hemodialysis took place predose in Period 1 and from 0.5 to 4.5 hours after dosing in Period 2. Data for healthy participants are from Part 1. Method of dispersion used for these data is geometric %CV.
Time frame: Predose and 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, 12, 24, 36, 48, 60, and 72 hours after dosing on Day 1 of Period 1 and 2, and 2.5, 3.5, and 4 hours after dosing on Day 1 of Period 2
Population: All participants who received MK-3866 infusion. Healthy participants were those who matched gender, and mean age and BMI of the comparator experimental group(s).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Mild Renal Impairment (RI) | Part 2: t1/2 of Plasma MK-3866 | 20.9 Hours | Geometric Coefficient of Variation 21.6 |
| Part 1: Moderate Renal Impairment | Part 2: t1/2 of Plasma MK-3866 | 20.0 Hours | Geometric Coefficient of Variation 18 |
| Part 1: Healthy Participants (Mild + Moderate RI) | Part 2: t1/2 of Plasma MK-3866 | 6.81 Hours | Geometric Coefficient of Variation 13.2 |
Primary
Part 2: Tmax of Plasma MK-3866
Plasma samples were collected at pre-specified time points and Tmax was assessed. Plasma concentrations of MK-3866 were determined using HPLC-MS/MS. For ESRD participants, hemodialysis took place predose in Period 1 and from 0.5 to 4.5 hours after dosing in Period 2. Data for healthy participants are from Part 1.
Time frame: Predose and 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, 12, 24, 36, 48, 60, and 72 hours after dosing on Day 1 of Period 1 and 2, and 2.5, 3.5, and 4 hours after dosing on Day 1 of Period 2
Population: All participants who received MK-3866 infusion. Healthy participants were those who matched gender, and mean age and BMI of the comparator experimental group(s).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: Mild Renal Impairment (RI) | Part 2: Tmax of Plasma MK-3866 | 0.50 Hours |
| Part 1: Moderate Renal Impairment | Part 2: Tmax of Plasma MK-3866 | 0.50 Hours |
| Part 1: Healthy Participants (Mild + Moderate RI) | Part 2: Tmax of Plasma MK-3866 | 0.48 Hours |
Primary
Part 2: Vz of Plasma MK-3866
Plasma samples were collected at pre-specified time points and Vz was assessed. Plasma concentrations of MK-3866 were determined using HPLC-MS/MS. For ESRD participants, hemodialysis took place predose in Period 1 and from 0.5 to 4.5 hours after dosing in Period 2. Data for healthy participants are from Part 1. Method of dispersion used for these data is geometric %CV.
Time frame: Predose and 0.5, 0.75, 1, 1.5, 2, 3, 4.5, 6, 8, 10, 12, 24, 36, 48, 60, and 72 hours after dosing on Day 1 of Period 1 and 2, and 2.5, 3.5, and 4 hours after dosing on Day 1 of Period 2
Population: All participants who received MK-3866 infusion. Healthy participants were those who matched gender, and mean age and BMI of the comparator experimental group(s).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Mild Renal Impairment (RI) | Part 2: Vz of Plasma MK-3866 | 37.1 Liters | Geometric Coefficient of Variation 20 |
| Part 1: Moderate Renal Impairment | Part 2: Vz of Plasma MK-3866 | 89.1 Liters | Geometric Coefficient of Variation 12.2 |
| Part 1: Healthy Participants (Mild + Moderate RI) | Part 2: Vz of Plasma MK-3866 | 47.9 Liters | Geometric Coefficient of Variation 18.8 |
Secondary
Number of Participants Discontinuing the Study Due to an Adverse Event
An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE.
Time frame: Part 1: up to Day 14 after dosing; Part 2, Period 1: up to Day 14 after dosing (including ≥6 day washout period); Part 2, Period 2: up to Day 14 after dosing
Population: All participants who received MK-3866 infusion. Healthy participants were those who matched gender, and mean age and BMI of the comparator experimental group(s).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Mild Renal Impairment (RI) | Number of Participants Discontinuing the Study Due to an Adverse Event | 0 Participants |
| Part 1: Moderate Renal Impairment | Number of Participants Discontinuing the Study Due to an Adverse Event | 0 Participants |
| Part 1: Healthy Participants (Mild + Moderate RI) | Number of Participants Discontinuing the Study Due to an Adverse Event | 0 Participants |
| Part 1: Severe Renal Impairment | Number of Participants Discontinuing the Study Due to an Adverse Event | 1 Participants |
| Part 1: Healthy Participants (Severe RI) | Number of Participants Discontinuing the Study Due to an Adverse Event | 1 Participants |
| Part 1: Healthy Participants | Number of Participants Discontinuing the Study Due to an Adverse Event | 0 Participants |
Secondary
Number of Participants With at Least One Adverse Event (AE)
An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE.
Time frame: Part 1: up to Day 14 after dosing; Part 2, Period 1: up to Day 14 after dosing (including ≥6 day washout period); Part 2, Period 2: up to Day 14 after dosing
Population: All participants who received MK-3866 infusion. Healthy participants were those who matched gender, and mean age and BMI of the comparator experimental group(s).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Mild Renal Impairment (RI) | Number of Participants With at Least One Adverse Event (AE) | 3 Participants |
| Part 1: Moderate Renal Impairment | Number of Participants With at Least One Adverse Event (AE) | 3 Participants |
| Part 1: Healthy Participants (Mild + Moderate RI) | Number of Participants With at Least One Adverse Event (AE) | 1 Participants |
| Part 1: Severe Renal Impairment | Number of Participants With at Least One Adverse Event (AE) | 1 Participants |
| Part 1: Healthy Participants (Severe RI) | Number of Participants With at Least One Adverse Event (AE) | 1 Participants |
| Part 1: Healthy Participants | Number of Participants With at Least One Adverse Event (AE) | 1 Participants |
Secondary
Part 1: Fraction of MK-3866 Excretion (Urine) During Each Collection Interval (Fe0-24)
Urine samples were collected at pre-specified intervals and Fe0-24 was assessed. Fe0-24 was obtained by dividing the amount of MK-3866 excreted in each collection interval by the dose. Urine concentrations of MK-3866 were determined using HPLC-MS/MS.
Time frame: Predose and 0-4, 4-8, 8-12, and 12-24 hours after dosing on Day 1
Population: All participants who received MK-3866 infusion. Healthy participants were those who matched gender, and mean age and BMI of the comparator experimental group(s).
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| Part 1: Mild Renal Impairment (RI) | Part 1: Fraction of MK-3866 Excretion (Urine) During Each Collection Interval (Fe0-24) | 0.485 Fraction of MK-3866 Excreted |
| Part 1: Moderate Renal Impairment | Part 1: Fraction of MK-3866 Excretion (Urine) During Each Collection Interval (Fe0-24) | 0.346 Fraction of MK-3866 Excreted |
| Part 1: Healthy Participants (Mild + Moderate RI) | Part 1: Fraction of MK-3866 Excretion (Urine) During Each Collection Interval (Fe0-24) | 0.537 Fraction of MK-3866 Excreted |
| Part 1: Severe Renal Impairment | Part 1: Fraction of MK-3866 Excretion (Urine) During Each Collection Interval (Fe0-24) | 0.173 Fraction of MK-3866 Excreted |
| Part 1: Healthy Participants (Severe RI) | Part 1: Fraction of MK-3866 Excretion (Urine) During Each Collection Interval (Fe0-24) | 0.575 Fraction of MK-3866 Excreted |
90% CI: [0.74, 1.11]
90% CI: [0.47, 0.88]
90% CI: [0.21, 0.43]
Secondary
Part 1: Renal Clearance (CLr) of MK-3866
Urine samples were collected at pre-specified intervals and CLr was assessed. CLr was calculated as AE(t'-t)/AUC(t'-t), where t'-t is the longest interval of time during which AE and AUC are both obtained. Urine concentrations of MK-3866 were determined using HPLC-MS/MS.
Time frame: Predose and 0-4, 4-8, 8-12, and 12-24 hours after dosing on Day 1
Population: All participants who received MK-3866 infusion. Healthy participants were those who matched gender, and mean age and BMI of the comparator experimental group(s).
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| Part 1: Mild Renal Impairment (RI) | Part 1: Renal Clearance (CLr) of MK-3866 | 2.00 L/hr |
| Part 1: Moderate Renal Impairment | Part 1: Renal Clearance (CLr) of MK-3866 | 1.08 L/hr |
| Part 1: Healthy Participants (Mild + Moderate RI) | Part 1: Renal Clearance (CLr) of MK-3866 | 2.67 L/hr |
| Part 1: Severe Renal Impairment | Part 1: Renal Clearance (CLr) of MK-3866 | 0.377 L/hr |
| Part 1: Healthy Participants (Severe RI) | Part 1: Renal Clearance (CLr) of MK-3866 | 2.92 L/hr |
90% CI: [0.57, 0.98]
90% CI: [0.31, 0.53]
90% CI: [0.08, 0.22]
Secondary
Part 1: Total Amount of MK-3866 Excreted in the Urine Over 24 Hours (Ae0-24)
Urine samples were collected at pre-specified intervals and Ae0-24 was assessed. Ae0-24 was obtained by adding the amounts excreted over each collection interval. Urine concentrations of MK-3866 were determined using HPLC-MS/MS.
Time frame: Predose and 0-4, 4-8, 8-12, and 12-24 hours after dosing on Day 1
Population: All participants who received MK-3866 infusion. Healthy participants were those who matched gender, and mean age and BMI of the comparator experimental group(s).
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| Part 1: Mild Renal Impairment (RI) | Part 1: Total Amount of MK-3866 Excreted in the Urine Over 24 Hours (Ae0-24) | 97.1 mg |
| Part 1: Moderate Renal Impairment | Part 1: Total Amount of MK-3866 Excreted in the Urine Over 24 Hours (Ae0-24) | 69.2 mg |
| Part 1: Healthy Participants (Mild + Moderate RI) | Part 1: Total Amount of MK-3866 Excreted in the Urine Over 24 Hours (Ae0-24) | 107 mg |
| Part 1: Severe Renal Impairment | Part 1: Total Amount of MK-3866 Excreted in the Urine Over 24 Hours (Ae0-24) | 34.6 mg |
| Part 1: Healthy Participants (Severe RI) | Part 1: Total Amount of MK-3866 Excreted in the Urine Over 24 Hours (Ae0-24) | 115 mg |
90% CI: [0.21, 0.43]
90% CI: [0.74, 1.11]
90% CI: [0.47, 0.88]
Secondary
Part 2: Amount of MK-3866 Recovered From Each Dialysate Sample (AD)
Plasma dialysis samples were collected at pre-specified time points and AD was assessed. Concentrations of MK-3866 were determined using HPLC-MS/MS. Method of dispersion used for these data is geometric %CV.
Time frame: 0.5 (beginning of HD), 1, 1.5, 2, 2.5, 3, 3.5, 4, and 4.5 hours after dosing on Day 1 of Period 2
Population: All participants who received MK-3866 infusion and provided samples for the outcome. This outcome applied only to ESRD participants receiving HD after infusion of MK-3866 (Part 2, Period 2).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Mild Renal Impairment (RI) | Part 2: Amount of MK-3866 Recovered From Each Dialysate Sample (AD) | 0.5 hours after dosing | 0.946 mg | Geometric Coefficient of Variation 8.6 |
| Part 1: Mild Renal Impairment (RI) | Part 2: Amount of MK-3866 Recovered From Each Dialysate Sample (AD) | 1 hour after dosing | 0.736 mg | Geometric Coefficient of Variation 31.8 |
| Part 1: Mild Renal Impairment (RI) | Part 2: Amount of MK-3866 Recovered From Each Dialysate Sample (AD) | 1.5 hours after dosing | 0.576 mg | Geometric Coefficient of Variation 6.8 |
| Part 1: Mild Renal Impairment (RI) | Part 2: Amount of MK-3866 Recovered From Each Dialysate Sample (AD) | 2 hours after dosing | 0.408 mg | Geometric Coefficient of Variation 8.7 |
| Part 1: Mild Renal Impairment (RI) | Part 2: Amount of MK-3866 Recovered From Each Dialysate Sample (AD) | 2.5 hours after dosing | 0.327 mg | Geometric Coefficient of Variation 10.7 |
| Part 1: Mild Renal Impairment (RI) | Part 2: Amount of MK-3866 Recovered From Each Dialysate Sample (AD) | 3 hours after dosing | 0.272 mg | Geometric Coefficient of Variation 10.3 |
| Part 1: Mild Renal Impairment (RI) | Part 2: Amount of MK-3866 Recovered From Each Dialysate Sample (AD) | 3.5 hours after dosing | 0.224 mg | Geometric Coefficient of Variation 10.3 |
| Part 1: Mild Renal Impairment (RI) | Part 2: Amount of MK-3866 Recovered From Each Dialysate Sample (AD) | 4 hours after dosing | 0.173 mg | Geometric Coefficient of Variation 17.2 |
| Part 1: Mild Renal Impairment (RI) | Part 2: Amount of MK-3866 Recovered From Each Dialysate Sample (AD) | 4.5 hours after dosing | 0.158 mg | Geometric Coefficient of Variation 13.7 |
Secondary
Part 2: Area Under the Concentration-time Curve of MK-3866 in Plasma Entering the Dialyzer Line During the Dialysis Period (AUCD)
Plasma samples entering the dialyzer line were collected at pre-specified time points and AUCD was assessed. AUCD values were determined from the Ca versus time profile during the HD period, using the 'linear up, log down' calculation method. Concentrations of MK-3866 were determined using HPLC-MS/MS. Method of dispersion used for these data is geometric %CV.
Time frame: 0.5 (beginning of HD), 1, 1.5, 2, 2.5, 3, 3.5, 4, and 4.5 hours after dosing on Day 1 of Period 2
Population: All participants who received MK-3866 infusion and provided samples for the outcome. This outcome applied only to ESRD participants receiving HD after infusion of MK-3866 (Part 2, Period 2).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Mild Renal Impairment (RI) | Part 2: Area Under the Concentration-time Curve of MK-3866 in Plasma Entering the Dialyzer Line During the Dialysis Period (AUCD) | 29.4 µM*hr | Geometric Coefficient of Variation 14.3 |
Secondary
Part 2: Area Under the Concentration-time Curve of MK-3866 in Plasma Entering the Dialyzer Line From 0.75 to 4.5 Hours During the Dialysis Period (AUC[0.75-4.5]Ca)
Plasma samples entering the dialyzer line were collected at pre-specified time points and AUC\[0.75-4.5\]Ca was assessed. AUC\[0.75-4.5\]Ca values were determined from the Ca versus time profile from 0.75 to 4.5 hours during the HD period, using the 'linear up, log down' calculation method. Concentrations of MK-3866 were determined using HPLC-MS/MS. Method of dispersion used for these data is geometric %CV.
Time frame: 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, and 4.5 hours after dosing on Day 1 of Period 2
Population: All participants who received MK-3866 infusion and provided samples for the outcome. This outcome applied only to ESRD participants receiving HD after infusion of MK-3866 (Part 2, Period 2).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Mild Renal Impairment (RI) | Part 2: Area Under the Concentration-time Curve of MK-3866 in Plasma Entering the Dialyzer Line From 0.75 to 4.5 Hours During the Dialysis Period (AUC[0.75-4.5]Ca) | 23.9 µM*hr | Geometric Coefficient of Variation 19 |
Secondary
Part 2: Area Under the Concentration-time Curve of MK-3866 in Plasma Entering the Dialyzer Line From 0.75 to 4.5 Hours During the Dialysis Period (AUC[0.75-4.5]Cv)
Plasma samples entering the dialyzer line were collected at pre-specified time points and AUC\[0.75-4.5\]Cv was assessed. AUC\[0.75-4.5\]Cv values were determined from the Cv versus time profile from 0.75 to 4.5 hours during the HD period, using the 'linear up, log down' calculation method. Concentrations of MK-3866 were determined using HPLC-MS/MS. Method of dispersion used for these data is geometric %CV.
Time frame: 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, and 4.5 hours after dosing on Day 1 of Period 2
Population: All participants who received MK-3866 infusion and provided samples for the outcome. This outcome applied only to ESRD participants receiving HD after infusion of MK-3866 (Part 2, Period 2).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Mild Renal Impairment (RI) | Part 2: Area Under the Concentration-time Curve of MK-3866 in Plasma Entering the Dialyzer Line From 0.75 to 4.5 Hours During the Dialysis Period (AUC[0.75-4.5]Cv) | 13.6 µM*hr | Geometric Coefficient of Variation 12.2 |
Secondary
Part 2: Concentration of MK-3866 in Dialysate Samples (CD)
Plasma dialysis samples were collected at pre-specified time points and CD was assessed. Concentrations of MK-3866 were determined using HPLC-MS/MS.
Time frame: 0.5 (beginning of HD), 1, 1.5, 2, 2.5, 3, 3.5, 4, and 4.5 hours after dosing on Day 1 of Period 2
Population: All participants who received MK-3866 infusion and provided samples for the outcome. This outcome applied only to ESRD participants receiving HD after infusion of MK-3866 (Part 2, Period 2).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Mild Renal Impairment (RI) | Part 2: Concentration of MK-3866 in Dialysate Samples (CD) | 0.5 hours after dosing | 1.07 µM | Standard Deviation 1.84 |
| Part 1: Mild Renal Impairment (RI) | Part 2: Concentration of MK-3866 in Dialysate Samples (CD) | 1 hour after dosing | 3.02 µM | Standard Deviation 0.748 |
| Part 1: Mild Renal Impairment (RI) | Part 2: Concentration of MK-3866 in Dialysate Samples (CD) | 1.5 hours after dosing | 2.29 µM | Standard Deviation 0.153 |
| Part 1: Mild Renal Impairment (RI) | Part 2: Concentration of MK-3866 in Dialysate Samples (CD) | 2 hours after dosing | 1.62 µM | Standard Deviation 0.142 |
| Part 1: Mild Renal Impairment (RI) | Part 2: Concentration of MK-3866 in Dialysate Samples (CD) | 2.5 hours after dosing | 1.30 µM | Standard Deviation 0.134 |
| Part 1: Mild Renal Impairment (RI) | Part 2: Concentration of MK-3866 in Dialysate Samples (CD) | 3 hours after dosing | 1.08 µM | Standard Deviation 0.106 |
| Part 1: Mild Renal Impairment (RI) | Part 2: Concentration of MK-3866 in Dialysate Samples (CD) | 3.5 hours after dosing | 0.894 µM | Standard Deviation 0.0896 |
| Part 1: Mild Renal Impairment (RI) | Part 2: Concentration of MK-3866 in Dialysate Samples (CD) | 4 hours after dosing | 0.695 µM | Standard Deviation 0.114 |
| Part 1: Mild Renal Impairment (RI) | Part 2: Concentration of MK-3866 in Dialysate Samples (CD) | 4.5 hours after dosing | 0.542 µM | Standard Deviation 0.251 |
Secondary
Part 2: Concentration of MK-3866 in Plasma Entering the Dialyzer Line (Ca)
Plasma samples entering the dialyzer line were collected at pre-specified time points and Ca was assessed. Concentrations of MK-3866 were determined using HPLC-MS/MS. Method of dispersion used for these data is geometric %CV.
Time frame: 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, and 4.5 hours after dosing on Day 1 of Period 2
Population: All participants who received MK-3866 infusion and provided samples for the outcome. This outcome applied only to ESRD participants receiving HD after infusion of MK-3866 (Part 2, Period 2).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Mild Renal Impairment (RI) | Part 2: Concentration of MK-3866 in Plasma Entering the Dialyzer Line (Ca) | 0.75 hours after dosing | 17.6 µM | Geometric Coefficient of Variation 15.6 |
| Part 1: Mild Renal Impairment (RI) | Part 2: Concentration of MK-3866 in Plasma Entering the Dialyzer Line (Ca) | 1 hour after dosing | 12.0 µM | Geometric Coefficient of Variation 35.8 |
| Part 1: Mild Renal Impairment (RI) | Part 2: Concentration of MK-3866 in Plasma Entering the Dialyzer Line (Ca) | 1.5 hours after dosing | 8.67 µM | Geometric Coefficient of Variation 33.1 |
| Part 1: Mild Renal Impairment (RI) | Part 2: Concentration of MK-3866 in Plasma Entering the Dialyzer Line (Ca) | 2 hours after dosing | 7.25 µM | Geometric Coefficient of Variation 10.8 |
| Part 1: Mild Renal Impairment (RI) | Part 2: Concentration of MK-3866 in Plasma Entering the Dialyzer Line (Ca) | 2.5 hours after dosing | 5.75 µM | Geometric Coefficient of Variation 8.5 |
| Part 1: Mild Renal Impairment (RI) | Part 2: Concentration of MK-3866 in Plasma Entering the Dialyzer Line (Ca) | 3 hours after dosing | 4.32 µM | Geometric Coefficient of Variation 35.8 |
| Part 1: Mild Renal Impairment (RI) | Part 2: Concentration of MK-3866 in Plasma Entering the Dialyzer Line (Ca) | 3.5 hours after dosing | 3.98 µM | Geometric Coefficient of Variation 10.3 |
| Part 1: Mild Renal Impairment (RI) | Part 2: Concentration of MK-3866 in Plasma Entering the Dialyzer Line (Ca) | 4 hours after dosing | 2.98 µM | Geometric Coefficient of Variation 31.8 |
| Part 1: Mild Renal Impairment (RI) | Part 2: Concentration of MK-3866 in Plasma Entering the Dialyzer Line (Ca) | 4.5 hours after dosing | 2.57 µM | Geometric Coefficient of Variation 31 |
Secondary
Part 2: Concentration of MK-3866 in Plasma Exiting the Dialyzer Line (Cv)
Plasma samples exiting the dialyzer line were collected at pre-specified time points and Cv was assessed. Concentrations of MK-3866 were determined using HPLC-MS/MS. Method of dispersion used for these data is geometric %CV.
Time frame: 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, and 4.5 hours after dosing on Day 1 of Period 2
Population: All participants who received MK-3866 infusion and provided samples for the outcome. This outcome applied only to ESRD participants receiving HD after infusion of MK-3866 (Part 2, Period 2).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Mild Renal Impairment (RI) | Part 2: Concentration of MK-3866 in Plasma Exiting the Dialyzer Line (Cv) | 0.75 hours after dosing | 8.32 µM | Geometric Coefficient of Variation 20.7 |
| Part 1: Mild Renal Impairment (RI) | Part 2: Concentration of MK-3866 in Plasma Exiting the Dialyzer Line (Cv) | 1 hour after dosing | 7.16 µM | Geometric Coefficient of Variation 24 |
| Part 1: Mild Renal Impairment (RI) | Part 2: Concentration of MK-3866 in Plasma Exiting the Dialyzer Line (Cv) | 1.5 hours after dosing | 5.17 µM | Geometric Coefficient of Variation 25.1 |
| Part 1: Mild Renal Impairment (RI) | Part 2: Concentration of MK-3866 in Plasma Exiting the Dialyzer Line (Cv) | 2 hours after dosing | 3.71 µM | Geometric Coefficient of Variation 10.5 |
| Part 1: Mild Renal Impairment (RI) | Part 2: Concentration of MK-3866 in Plasma Exiting the Dialyzer Line (Cv) | 2.5 hours after dosing | 2.92 µM | Geometric Coefficient of Variation 11.4 |
| Part 1: Mild Renal Impairment (RI) | Part 2: Concentration of MK-3866 in Plasma Exiting the Dialyzer Line (Cv) | 3 hours after dosing | 2.69 µM | Geometric Coefficient of Variation 21 |
| Part 1: Mild Renal Impairment (RI) | Part 2: Concentration of MK-3866 in Plasma Exiting the Dialyzer Line (Cv) | 3.5 hours after dosing | 2.12 µM | Geometric Coefficient of Variation 25.2 |
| Part 1: Mild Renal Impairment (RI) | Part 2: Concentration of MK-3866 in Plasma Exiting the Dialyzer Line (Cv) | 4 hours after dosing | 2.10 µM | Geometric Coefficient of Variation 33.8 |
| Part 1: Mild Renal Impairment (RI) | Part 2: Concentration of MK-3866 in Plasma Exiting the Dialyzer Line (Cv) | 4.5 hours after dosing | 1.66 µM | Geometric Coefficient of Variation 49.4 |
Secondary
Part 2: Cumulative Amount of MK-3866 Recovered From the Dialysate (AD,Total)
Plasma dialysis samples were collected at pre-specified time points and AD,total was assessed. AD,total was obtained by integrating the rr versus time profile over the dialysis session duration, using actual times relative to the start time of dialysis. Concentrations of MK-3866 were determined using HPLC-MS/MS. Method of dispersion used for these data is geometric %CV.
Time frame: 0.5 (beginning of HD), 1, 1.5, 2, 2.5, 3, 3.5, 4, and 4.5 hours after dosing on Day 1 of Period 2
Population: All participants who received MK-3866 infusion and provided samples for the outcome. This outcome applied only to ESRD participants receiving HD after infusion of MK-3866 (Part 2, Period 2).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Mild Renal Impairment (RI) | Part 2: Cumulative Amount of MK-3866 Recovered From the Dialysate (AD,Total) | 89.0 mg | Geometric Coefficient of Variation 9.3 |
Secondary
Part 2: Dialysis Clearance of MK-3866 Based on Plasma (CLD,Plasma)
Plasma dialysis samples were collected at pre-specified time points and CLD was assessed. CLD was calculated as Q x R x (AUC\[1-4.5\]Ca - AUC\[1-4.5\]Cv) / AUC\[1-4.5\]Ca, where Q is the flow rate of blood through the dialyzer, and R is the ratio of blood drug concentration to plasma drug concentration. Concentrations of MK-3866 were determined using HPLC-MS/MS. Method of dispersion used for these data is geometric %CV.
Time frame: 0.5 (beginning of HD), 1, 1.5, 2, 2.5, 3, 3.5, 4, and 4.5 hours after dosing on Day 1 of Period 2
Population: All participants who received MK-3866 infusion and provided samples for the outcome. This outcome applied only to ESRD participants receiving HD after infusion of MK-3866 (Part 2, Period 2).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Mild Renal Impairment (RI) | Part 2: Dialysis Clearance of MK-3866 Based on Plasma (CLD,Plasma) | 4.81 L/hr | Geometric Coefficient of Variation 201.1 |
Secondary
Part 2: Fraction of MK-3866 Excretion (Urine) During Each Collection Interval (Fe0-24)
Urine samples were collected at pre-specified intervals and Fe0-24 was assessed. Fe0-24 was obtained by dividing the amount of MK-3866 excreted in each collection interval by the dose. Urine concentrations of MK-3866 were determined using HPLC-MS/MS. Method of dispersion used for these data is geometric %CV.
Time frame: Predose and 0-4, 4-8, 8-12, and 12-24 hours after dosing on Day 1 of Period 1 and Period 2
Population: All participants who received MK-3866 infusion and provided samples for the outcome. Healthy participants were those who matched gender, and mean age and BMI of the comparator experimental group(s).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Mild Renal Impairment (RI) | Part 2: Fraction of MK-3866 Excretion (Urine) During Each Collection Interval (Fe0-24) | 0.0216 Fraction of MK-3866 Excreted | Geometric Coefficient of Variation 42.6 |
| Part 1: Moderate Renal Impairment | Part 2: Fraction of MK-3866 Excretion (Urine) During Each Collection Interval (Fe0-24) | 0.0111 Fraction of MK-3866 Excreted | Geometric Coefficient of Variation 4.4 |
| Part 1: Healthy Participants (Mild + Moderate RI) | Part 2: Fraction of MK-3866 Excretion (Urine) During Each Collection Interval (Fe0-24) | 0.574 Fraction of MK-3866 Excreted | Geometric Coefficient of Variation 24.9 |
Secondary
Part 2: Hemodialysis Clearance of MK-3866 Based on the Dialysate(CLD,Dialysate)
Plasma dialysis samples were collected at pre-specified time points and CLD,dialysate was assessed. CLD,dialysate was calculated as AD.total / AUCD. Concentrations of MK-3866 were determined using HPLC-MS/MS. Method of dispersion used for these data is geometric %CV.
Time frame: 0.5 (beginning of HD), 1, 1.5, 2, 2.5, 3, 3.5, 4, and 4.5 hours after dosing on Day 1 of Period 2
Population: All participants who received MK-3866 infusion and provided samples for the outcome. This outcome applied only to ESRD participants receiving HD after infusion of MK-3866 (Part 2, Period 2).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Mild Renal Impairment (RI) | Part 2: Hemodialysis Clearance of MK-3866 Based on the Dialysate(CLD,Dialysate) | 6.01 L/hr | Geometric Coefficient of Variation 13.2 |
Secondary
Part 2: Rate of Removal of MK-3866 From the Dialysate (rr)
Plasma dialysis samples were collected at pre-specified time points and rr was assessed. rr was calculated as CD x dialysate flow rate. Concentrations of MK-3866 were determined using HPLC-MS/MS. Method of dispersion used for these data is geometric %CV.
Time frame: 0.5 (beginning of HD), 1, 1.5, 2, 2.5, 3, 3.5, 4, and 4.5 hours after dosing on Day 1 of Period 2
Population: All participants who received MK-3866 infusion and provided samples for the outcome. This outcome applied only to ESRD participants receiving HD after infusion of MK-3866 (Part 2, Period 2).
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1: Mild Renal Impairment (RI) | Part 2: Rate of Removal of MK-3866 From the Dialysate (rr) | 1.5 hours after dosing | 34.6 mg/hr | Geometric Coefficient of Variation 6.8 |
| Part 1: Mild Renal Impairment (RI) | Part 2: Rate of Removal of MK-3866 From the Dialysate (rr) | 2 hours after dosing | 24.5 mg/hr | Geometric Coefficient of Variation 8.7 |
| Part 1: Mild Renal Impairment (RI) | Part 2: Rate of Removal of MK-3866 From the Dialysate (rr) | 2.5 hours after dosing | 19.6 mg/hr | Geometric Coefficient of Variation 10.7 |
| Part 1: Mild Renal Impairment (RI) | Part 2: Rate of Removal of MK-3866 From the Dialysate (rr) | 3 hours after dosing | 16.3 mg/hr | Geometric Coefficient of Variation 10.3 |
| Part 1: Mild Renal Impairment (RI) | Part 2: Rate of Removal of MK-3866 From the Dialysate (rr) | 3.5 hours after dosing | 13.5 mg/hr | Geometric Coefficient of Variation 10.3 |
| Part 1: Mild Renal Impairment (RI) | Part 2: Rate of Removal of MK-3866 From the Dialysate (rr) | 4 hours after dosing | 10.4 mg/hr | Geometric Coefficient of Variation 17.2 |
| Part 1: Mild Renal Impairment (RI) | Part 2: Rate of Removal of MK-3866 From the Dialysate (rr) | 4.5 hours after dosing | 9.51 mg/hr | Geometric Coefficient of Variation 13.7 |
| Part 1: Mild Renal Impairment (RI) | Part 2: Rate of Removal of MK-3866 From the Dialysate (rr) | 0.5 hours after dosing | 56.7 mg/hr | Geometric Coefficient of Variation 8.6 |
| Part 1: Mild Renal Impairment (RI) | Part 2: Rate of Removal of MK-3866 From the Dialysate (rr) | 1 hour after dosing | 44.2 mg/hr | Geometric Coefficient of Variation 31.8 |
Secondary
Part 2: Renal Clearance (CLr) of MK-3866
Urine samples were collected at pre-specified intervals and CLr was assessed. CLr was calculated as AE(t'-t)/AUC(t'-t), where t'-t is the longest interval of time during which AE and AUC are both obtained. Urine concentrations of MK-3866 were determined using HPLC-MS/MS. Method of dispersion used for these data is geometric %CV.
Time frame: Predose and 0-4, 4-8, 8-12, and 12-24 hours after dosing on Day 1 of Period 1 and Period 2
Population: All participants who received MK-3866 infusion and provided samples for the outcome. Healthy participants were those who matched gender, and mean age and BMI of the comparator experimental group(s).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Mild Renal Impairment (RI) | Part 2: Renal Clearance (CLr) of MK-3866 | 0.0474 L/hr | Geometric Coefficient of Variation 8.5 |
| Part 1: Moderate Renal Impairment | Part 2: Renal Clearance (CLr) of MK-3866 | 0.0558 L/hr | Geometric Coefficient of Variation 15.8 |
| Part 1: Healthy Participants (Mild + Moderate RI) | Part 2: Renal Clearance (CLr) of MK-3866 | 2.92 L/hr | Geometric Coefficient of Variation 32.1 |
Secondary
Part 2: Total Amount of MK-3866 Excreted Unchanged in the Urine Over the Period of 24 Hours (Ae0-24)
Urine samples were collected at pre-specified intervals and Ae0-24 was assessed. Ae0-24 was obtained by adding the amounts excreted over each collection interval. Urine concentrations of MK-3866 were determined using HPLC-MS/MS. Method of dispersion used for these data is geometric %CV.
Time frame: Predose and 0-4, 4-8, 8-12, and 12-24 hours after dosing on Day 1 of Period 1 and Period 2
Population: All participants who received MK-3866 infusion and provided samples for the outcome. Healthy participants were those who matched gender, and mean age and BMI of the comparator experimental group(s).
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1: Mild Renal Impairment (RI) | Part 2: Total Amount of MK-3866 Excreted Unchanged in the Urine Over the Period of 24 Hours (Ae0-24) | 4.31 mg | Geometric Coefficient of Variation 42.6 |
| Part 1: Moderate Renal Impairment | Part 2: Total Amount of MK-3866 Excreted Unchanged in the Urine Over the Period of 24 Hours (Ae0-24) | 2.21 mg | Geometric Coefficient of Variation 4.4 |
| Part 1: Healthy Participants (Mild + Moderate RI) | Part 2: Total Amount of MK-3866 Excreted Unchanged in the Urine Over the Period of 24 Hours (Ae0-24) | 115 mg | Geometric Coefficient of Variation 24.9 |