CompletedNCT03259087Updated Apr 19, 2019Results posted

Pharmacokinetics (PK) and Safety of a Single Intravenous (IV) Dose of MK-3866 in Participants With Impaired Renal Function and in Healthy Controls (MK-3866-005)

A Phase 1 interventional study of MK-3866 in Renal Impairment, sponsored by Merck Sharp & Dohme LLC. Completed at 2 sites in United States. Open to participants aged 18 Years to 75 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2019-04-19.

Sponsored by Merck Sharp & Dohme LLC (part of Merck & Co., Inc) · Phase 1, Interventional, and Treatment

Phase: Phase 1
Study type: Interventional
Enrollment: 42
Allocation: Non-randomized
Ages: 18 Years to 75 Years
Sex: All

Study 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.

Read the 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.

Conditions studied

Renal Impairment

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Renal Insufficiency 2,030

In context

Renal Insufficiency

2,030 studies on the registry are indexed under Renal Insufficiency; 168 are open to participants now.

This study's enrollment of 42 is close to the median of 43 across 1,534 interventional studies indexed under Renal Insufficiency.

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Lead sponsor

Merck Sharp & Dohme LLC is the lead sponsor of 2,159 studies on the registry; 133 are open to participants now.

Of its 497 completed or terminated interventional studies of FDA-regulated products, 369 (74%) have results posted.

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Who can participate

Ages eligible: 18 Years to 75 Years
Sexes eligible: All
Accepts healthy volunteers: Yes

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

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

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

Study design

Phase: Phase 1
Primary purpose: Treatment
Allocation: Non-randomized
Intervention model: Parallel assignment
Masking: None (open label)
Enrollment: 42 participants (actual)

Study arms

Experimental
Part 1: Mild Renal Impairment
Participants receive a single IV infusion of 200 mg MK-3866 over 30 minutes on Day 1.
Drug: MK-3866
Experimental
Part 1: Moderate Renal Impairment
Participants receive a single IV infusion of 200 mg MK-3866 over 30 minutes on Day 1.
Drug: MK-3866
Experimental
Part 1: Severe Renal Impairment
Participants receive a single IV infusion of 200 mg MK-3866 over 30 minutes on Day 1.
Drug: MK-3866
Experimental
Part 1: Healthy Participants
Participants receive a single IV infusion of 200 mg MK-3866 over 30 minutes on Day 1.
Drug: MK-3866
Experimental
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.
Drug: MK-3866

Interventions

DrugMK-3866
Single IV infusion of 200 mg administered over 30 minutes (±5 minutes) on Day 1 of each treatment period.

What researchers measure

Primary outcomes

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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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

Secondary outcomes

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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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

Results

Posted Apr 19, 2019

Participant flow

Part 1 and Period 1 of Part 2

Participant flow — Part 1 and Period 1 of Part 2
Milestone	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
Started	8	8	8	10	8
Completed	8	8	8	10	7
Not completed	0	0	0	0	1
Withdrew: Adverse event	0	0	0	0	1

Period 2 of Part 2

Participant flow — Period 2 of Part 2
Milestone	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
Started	0	0	0	0	7
Completed	0	0	0	0	6
Not completed	0	0	0	0	1
Withdrew: Adverse event	0	0	0	0	1

Outcome measures

PrimaryPart 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
Reported as:: Geometric least squares mean · µM*hr

Part 1: Area Under the Plasma Concentration-time Curve of MK-3866 From Time Zero to Infinity (AUC0-inf)
µM*hr	Part 1: Mild Renal Impairment (RI)	Part 1: Moderate Renal Impairment	Part 1: Healthy Participants (Mild + Moderate RI)	Part 1: Severe Renal Impairment	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)	104 (87.2 to 125)	141 (115 to 174)	83.5 (75.0 to 92.9)	244 (169 to 352)	81.8 (72.4 to 92.4)

Statistical analysis

Part 1: Mild Renal Impairment (RI) vs Part 1: Healthy Participants (Mild + Moderate RI) · Geometric least squares mean ratio (gmr): 1.25 · 90% CI 1.07 to 1.47GMR is ratio of Experimental Group / Healthy Group
Part 1: Moderate Renal Impairment vs Part 1: Healthy Participants (Mild + Moderate RI) · Geometric least squares mean ratio (gmr): 1.70 · 90% CI 1.42 to 2.02GMR is ratio of Experimental Group / Healthy Group
Part 1: Severe Renal Impairment vs Part 1: Healthy Participants (Severe RI) · Geometric least squares mean ratio (gmr): 2.98 · 90% CI 2.20 to 4.04GMR is ratio of Experimental Group / Healthy Group

PrimaryPart 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
Reported as:: Geometric least squares mean · µM*hr

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)
µM*hr	Part 1: Mild Renal Impairment (RI)	Part 1: Moderate Renal Impairment	Part 1: Healthy Participants (Mild + Moderate RI)	Part 1: Severe Renal Impairment	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)	103 (86.7 to 123)	139 (114 to 170)	83.0 (74.5 to 92.5)	237 (166 to 338)	81.4 (72.0 to 92.0)

Statistical analysis

Part 1: Mild Renal Impairment (RI) vs Part 1: Healthy Participants (Mild + Moderate RI) · Geometric least squares mean ratio (gmr): 1.25 · 90% CI 1.06 to 1.46GMR is ratio of Experimental Group / Healthy Group
Part 1: Moderate Renal Impairment vs Part 1: Healthy Participants (Mild + Moderate RI) · Geometric least squares mean ratio (gmr): 1.68 · 90% CI 1.41 to 1.99GMR is ratio of Experimental Group / Healthy Group
Part 1: Severe Renal Impairment vs Part 1: Healthy Participants (Severe RI) · Geometric least squares mean ratio (gmr): 2.91 · 90% CI 2.17 to 3.90GMR is ratio of Experimental Group / Healthy Group

PrimaryPart 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
Reported as:: Geometric least squares mean · µM*hr

Part 1: Area Under the Plasma Concentration-time Curve of MK-3866 From Time Zero to 24 Hours After Dosing (AUC0-24)
µM*hr	Part 1: Mild Renal Impairment (RI)	Part 1: Moderate Renal Impairment	Part 1: Healthy Participants (Mild + Moderate RI)	Part 1: Severe Renal Impairment	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)	96.2 (82.0 to 113)	127 (107 to 152)	79.7 (71.6 to 88.7)	182 (136 to 243)	78.1 (69.2 to 88.3)

Statistical analysis

Part 1: Mild Renal Impairment (RI) vs Part 1: Healthy Participants (Mild + Moderate RI) · Geometric least squares mean ratio (gmr): 1.21 · 90% CI 1.04 to 1.40GMR is ratio of Experimental Group / Healthy Group
Part 1: Moderate Renal Impairment vs Part 1: Healthy Participants (Mild + Moderate RI) · Geometric least squares mean ratio (gmr): 1.59 · 90% CI 1.36 to 1.86GMR is ratio of Experimental Group / Healthy Group
Part 1: Severe Renal Impairment vs Part 1: Healthy Participants (Severe RI) · Geometric least squares mean ratio (gmr): 2.32 · 90% CI 1.82 to 2.97GMR is ratio of Experimental Group / Healthy Group

PrimaryPart 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
Reported as:: Geometric least squares mean · µM

Part 1: Plasma Concentration of MK-3866 at the End of the Infusion (Ceoi)
µM	Part 1: Mild Renal Impairment (RI)	Part 1: Moderate Renal Impairment	Part 1: Healthy Participants (Mild + Moderate RI)	Part 1: Severe Renal Impairment	Part 1: Healthy Participants (Severe RI)
Part 1: Plasma Concentration of MK-3866 at the End of the Infusion (Ceoi)	26.6 (22.3 to 31.8)	27.7 (24.2 to 31.7)	27.0 (23.9 to 30.5)	29.7 (25.4 to 34.7)	26.9 (23.7 to 30.5)

Statistical analysis

Part 1: Mild Renal Impairment (RI) vs Part 1: Healthy Participants (Mild + Moderate RI) · Geometric least squares mean ratio (gmr): 0.99 · 90% CI 0.84 to 1.16GMR is ratio of Experimental Group / Healthy Group
Part 1: Moderate Renal Impairment vs Part 1: Healthy Participants (Mild + Moderate RI) · Geometric least squares mean ratio (gmr): 1.03 · 90% CI 0.90 to 1.18GMR is ratio of Experimental Group / Healthy Group
Part 1: Severe Renal Impairment vs Part 1: Healthy Participants (Severe RI) · Geometric least squares mean ratio (gmr): 1.11 · 90% CI 0.95 to 1.29GMR is ratio of Experimental Group / Healthy Group

PrimaryPart 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
Reported as:: Mean · µM

Part 1: Maximum Plasma Concentration of MK-3866 (Cmax)
µM	Part 1: Mild Renal Impairment (RI)	Part 1: Moderate Renal Impairment	Part 1: Severe Renal Impairment	Part 1: Healthy Participants (Mild, Moderate, and Severe RI)
Part 1: Maximum Plasma Concentration of MK-3866 (Cmax)	27.4 (26.0 to 28.9)	28.0 (26.4 to 29.7)	28.7 (26.4 to 31.2)	26.7 (24.8 to 28.8)

PrimaryPart 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
Reported as:: Geometric least squares mean · L/hr

Part 1: Plasma Clearance of MK-3866 (CL)
L/hr	Part 1: Mild Renal Impairment (RI)	Part 1: Moderate Renal Impairment	Part 1: Healthy Participants (Mild + Moderate RI)	Part 1: Severe Renal Impairment	Part 1: Healthy Participants (Severe RI)
Part 1: Plasma Clearance of MK-3866 (CL)	3.80 (3.17 to 4.55)	2.80 (2.28 to 3.44)	4.75 (4.27 to 5.28)	1.62 (1.12 to 2.35)	4.85 (4.29 to 5.48)

Statistical analysis

Part 1: Mild Renal Impairment (RI) vs Part 1: Healthy Participants (Mild + Moderate RI) · Geometric least squares mean ratio (gmr): 0.80 · 90% CI 0.68 to 0.94GMR is ratio of Experimental Group / Healthy Group
Part 1: Moderate Renal Impairment vs Part 1: Healthy Participants (Mild + Moderate RI) · Geometric least squares mean ratio (gmr): 0.59 · 90% CI 0.49 to 0.70GMR is ratio of Experimental Group / Healthy Group
Part 1: Severe Renal Impairment vs Part 1: Healthy Participants (Severe RI) · Geometric least squares mean ratio (gmr): 0.34 · 90% CI 0.25 to 0.45GMR is ratio of Experimental Group / Healthy Group

PrimaryPart 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
Reported as:: Median · Hours

Part 1: Time to Maximum Plasma Concentration of MK-3866 (Tmax)
Hours	Part 1: Mild Renal Impairment (RI)	Part 1: Moderate Renal Impairment	Part 1: Healthy Participants (Mild + Moderate RI)	Part 1: Severe Renal Impairment	Part 1: Healthy Participants (Severe RI)
Part 1: Time to Maximum Plasma Concentration of MK-3866 (Tmax)	0.50 (0.47 to 0.50)	0.49 (0.47 to 0.50)	0.50 (0.47 to 0.50)	0.50 (0.47 to 0.53)	0.50 (0.47 to 0.50)

PrimaryPart 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
Reported as:: Geometric mean · Hours

Part 1: Elimination Terminal Half-life of Plasma MK-3866 (t1/2)
Hours	Part 1: Mild Renal Impairment (RI)	Part 1: Moderate Renal Impairment	Part 1: Healthy Participants (Mild + Moderate RI)	Part 1: Severe Renal Impairment	Part 1: Healthy Participants (Severe RI)
Part 1: Elimination Terminal Half-life of Plasma MK-3866 (t1/2)	7.38 ± 13.3	8.23 ± 17.0	7.00 ± 12.7	14.7 ± 17.8	6.90 ± 13.0

PrimaryPart 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
Reported as:: Geometric mean · Liters

Part 1: Volume of Distribution of Plasma MK-3866 (Vz)
Liters	Part 1: Mild Renal Impairment (RI)	Part 1: Moderate Renal Impairment	Part 1: Healthy Participants (Mild + Moderate RI)	Part 1: Severe Renal Impairment	Part 1: Healthy Participants (Severe RI)
Part 1: Volume of Distribution of Plasma MK-3866 (Vz)	40.4 ± 18.3	33.3 ± 18.0	48.0 ± 17.3	34.4 ± 29.5	48.3 ± 17.7

PrimaryPart 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
Reported as:: Geometric least squares mean · µM*hr

Part 2: AUC0-inf of Plasma MK-3866
µM*hr	Part 2, Period 1: ESRD Undergoing HD (Dosed After HD)	Part 2, Period 2: ESRD Undergoing HD (Dosed Before HD)	Part 1: Healthy Participants (ESRD)
Part 2: AUC0-inf of Plasma MK-3866	323 (260 to 401)	129 (103 to 161)	81.3 (70.6 to 93.7)

Statistical analysis

Part 2, Period 1: ESRD Undergoing HD (Dosed After HD) vs Part 1: Healthy Participants (ESRD) · Geometric least squares mean ratio (gmr): 3.97 · 90% CI 3.26 to 4.82GMR is ratio of Experimental Group / Healthy Group
Part 2, Period 2: ESRD Undergoing HD (Dosed Before HD) vs Part 1: Healthy Participants (ESRD) · Geometric least squares mean ratio (gmr): 1.58 · 90% CI 1.30 to 1.92GMR is ratio of Experimental Group / Healthy Group

PrimaryPart 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
Reported as:: Geometric least squares mean · µM*hr

Part 2: AUC0-last of Plasma MK-3866
µM*hr	Part 2, Period 1: ESRD Undergoing HD (Dosed After HD)	Part 2, Period 2: ESRD Undergoing HD (Dosed Before HD)	Part 1: Healthy Participants (ESRD)
Part 2: AUC0-last of Plasma MK-3866	294 (241 to 358)	118 (97.4 to 144)	80.9 (70.2 to 93.3)

Statistical analysis

Part 2, Period 1: ESRD Undergoing HD (Dosed After HD) vs Part 1: Healthy Participants (ESRD) · Geometric least squares mean ratio (gmr): 3.63 · 90% CI 3.03 to 4.36GMR is ratio of Experimental Group / Healthy Group
Part 2, Period 2: ESRD Undergoing HD (Dosed Before HD) vs Part 1: Healthy Participants (ESRD) · Geometric least squares mean ratio (gmr): 1.46 · 90% CI 1.22 to 1.75GMR is ratio of Experimental Group / Healthy Group

PrimaryPart 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
Reported as:: Geometric least squares mean · µM*hr

Part 2: AUC0-24 of Plasma MK-3866
µM*hr	Part 2, Period 1: ESRD Undergoing HD (Dosed After HD)	Part 2, Period 2: ESRD Undergoing HD (Dosed Before HD)	Part 1: Healthy Participants (ESRD)
Part 2: AUC0-24 of Plasma MK-3866	203 (174 to 238)	84.7 (74.6 to 96.1)	77.8 (67.5 to 89.6)

Statistical analysis

Part 2, Period 1: ESRD Undergoing HD (Dosed After HD) vs Part 1: Healthy Participants (ESRD) · Geometric least squares mean ratio (gmr): 2.61 · 90% CI 2.23 to 3.06GMR is ratio of Experimental Group / Healthy Group
Part 2, Period 2: ESRD Undergoing HD (Dosed Before HD) vs Part 1: Healthy Participants (ESRD) · Geometric least squares mean ratio (gmr): 1.09 · 90% CI 0.95 to 1.25GMR is ratio of Experimental Group / Healthy Group

PrimaryPart 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
Reported as:: Geometric least squares mean · µM

Part 2: Ceoi of Plasma MK-3866
µM	Part 2, Period 1: ESRD Undergoing HD (Dosed After HD)	Part 2, Period 2: ESRD Undergoing HD (Dosed Before HD)	Part 1: Healthy Participants (ESRD)
Part 2: Ceoi of Plasma MK-3866	26.3 (22.7 to 30.3)	25.3 (19.1 to 33.4)	26.8 (23.1 to 31.0)

Statistical analysis

Part 2, Period 1: ESRD Undergoing HD (Dosed After HD) vs Part 1: Healthy Participants (ESRD) · Geometric least squares mean ratio (gmr): 0.98 · 90% CI 0.84 to 1.14GMR is ratio of Experimental Group / Healthy Group
Part 2, Period 2: ESRD Undergoing HD (Dosed Before HD) vs Part 1: Healthy Participants (ESRD) · Geometric least squares mean ratio (gmr): 0.94 · 90% CI 0.75 to 1.20GMR is ratio of Experimental Group / Healthy Group

PrimaryPart 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
Reported as:: Geometric least squares mean · µM

Part 2: Cmax of Plasma MK-3866
µM	Part 2, Period 1: ESRD Undergoing HD (Dosed After HD)	Part 2, Period 2: ESRD Undergoing HD (Dosed Before HD)	Part 1: Healthy Participants (ESRD)
Part 2: Cmax of Plasma MK-3866	26.6 (23.1 to 30.6)	25.3 (19.1 to 33.4)	26.8 (23.1 to 31.0)

Statistical analysis

Part 2, Period 1: ESRD Undergoing HD (Dosed After HD) vs Part 1: Healthy Participants (ESRD) · Geometric least squares mean ratio (gmr): 0.99 · 90% CI 0.85 to 1.16GMR is ratio of Experimental Group / Healthy Group
Part 2, Period 2: ESRD Undergoing HD (Dosed Before HD) vs Part 1: Healthy Participants (ESRD) · Geometric least squares mean ratio (gmr): 0.94 · 90% CI 0.75 to 1.20GMR is ratio of Experimental Group / Healthy Group

PrimaryPart 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
Reported as:: Geometric mean · L/hr

Part 2: CL of Plasma MK-3866
L/hr	Part 2, Period 1: ESRD Undergoing HD (Dosed After HD)	Part 2, Period 2: ESRD Undergoing HD (Dosed Before HD)	Part 1: Healthy Participants (ESRD)
Part 2: CL of Plasma MK-3866	1.23 (0.989 to 1.53)	3.08 (2.47 to 3.85)	4.87 (4.23 to 5.61)

Statistical analysis

Part 2, Period 1: ESRD Undergoing HD (Dosed After HD) vs Part 1: Healthy Participants (ESRD) · Geometric least squares mean ratio (gmr): 0.25 · 90% CI 0.21 to 0.31GMR is ratio of Experimental Group / Healthy Group
Part 2, Period 2: ESRD Undergoing HD (Dosed Before HD) vs Part 1: Healthy Participants (ESRD) · Geometric least squares mean ratio (gmr): 0.63 · 95% CI 0.52 to 0.77GMR is ratio of Experimental Group / Healthy Group

PrimaryPart 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
Reported as:: Median · Hours

Part 2: Tmax of Plasma MK-3866
Hours	Part 2, Period 1: ESRD Undergoing HD (Dosed After HD)	Part 2, Period 2: ESRD Undergoing HD (Dosed Before HD)	Part 1: Healthy Participants (ESRD)
Part 2: Tmax of Plasma MK-3866	0.50 (0.50 to 0.75)	0.50 (0.50 to 0.50)	0.48 (0.47 to 0.50)

PrimaryPart 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
Reported as:: Geometric mean · Hours

Part 2: t1/2 of Plasma MK-3866
Hours	Part 2, Period 1: ESRD Undergoing HD (Dosed After HD)	Part 2, Period 2: ESRD Undergoing HD (Dosed Before HD)	Part 1: Healthy Participants (ESRD)
Part 2: t1/2 of Plasma MK-3866	20.9 ± 21.6	20.0 ± 18.0	6.81 ± 13.2

PrimaryPart 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
Reported as:: Geometric mean · Liters

Part 2: Vz of Plasma MK-3866
Liters	Part 2, Period 1: ESRD Undergoing HD (Dosed After HD)	Part 2, Period 2: ESRD Undergoing HD (Dosed Before HD)	Part 1: Healthy Participants (ESRD)
Part 2: Vz of Plasma MK-3866	37.1 ± 20.0	89.1 ± 12.2	47.9 ± 18.8

SecondaryPart 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
Reported as:: Geometric least squares mean · mg

Part 1: Total Amount of MK-3866 Excreted in the Urine Over 24 Hours (Ae0-24)
mg	Part 1: Mild Renal Impairment (RI)	Part 1: Moderate Renal Impairment	Part 1: Healthy Participants (Mild + Moderate RI)	Part 1: Severe Renal Impairment	Part 1: Healthy Participants (Severe RI)
Part 1: Total Amount of MK-3866 Excreted in the Urine Over 24 Hours (Ae0-24)	97.1 (79.6 to 118)	69.2 (48.4 to 98.8)	107 (89.0 to 130)	34.6 (22.7 to 52.6)	115 (96.4 to 137)

Statistical analysis

Part 1: Mild Renal Impairment (RI) vs Part 1: Healthy Participants (Mild + Moderate RI) · Geometric least squares mean ratio (gmr): 0.90 · 90% CI 0.74 to 1.11GMR is ratio of Experimental Group / Healthy Group
Part 1: Moderate Renal Impairment vs Part 1: Healthy Participants (Mild + Moderate RI) · Geometric least squares mean ratio (gmr): 0.64 · 90% CI 0.47 to 0.88GMR is ratio of Experimental Group / Healthy Group
Part 1: Severe Renal Impairment vs Part 1: Healthy Participants (Severe RI) · Geometric least squares mean ratio (gmr): 0.30 · 90% CI 0.21 to 0.43GMR is ratio of Experimental Group / Healthy Group

SecondaryPart 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
Reported as:: Geometric least squares mean · L/hr

Part 1: Renal Clearance (CLr) of MK-3866
L/hr	Part 1: Mild Renal Impairment (RI)	Part 1: Moderate Renal Impairment	Part 1: Healthy Participants (Mild + Moderate RI)	Part 1: Severe Renal Impairment	Part 1: Healthy Participants (Severe RI)
Part 1: Renal Clearance (CLr) of MK-3866	2.00 (1.50 to 2.66)	1.08 (0.801 to 1.45)	2.67 (2.18 to 3.27)	0.377 (0.200 to 0.710)	2.92 (2.33 to 3.65)

Statistical analysis

Part 1: Mild Renal Impairment (RI) vs Part 1: Healthy Participants (Mild + Moderate RI) · Geometric least squares mean ratio (gmr): 0.75 · 90% CI 0.57 to 0.98GMR is ratio of Experimental Group / Healthy Group
Part 1: Moderate Renal Impairment vs Part 1: Healthy Participants (Mild + Moderate RI) · Geometric least squares mean ratio (gmr): 0.40 · 90% CI 0.31 to 0.53GMR is ratio of Experimental Group / Healthy Group
Part 1: Severe Renal Impairment vs Part 1: Healthy Participants (Severe RI) · Geometric least squares mean ratio (gmr): 0.13 · 90% CI 0.08 to 0.22GMR is ratio of Experimental Group / Healthy Group

SecondaryPart 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
Reported as:: Geometric least squares mean · Fraction of MK-3866 Excreted

Part 1: Fraction of MK-3866 Excretion (Urine) During Each Collection Interval (Fe0-24)
Fraction of MK-3866 Excreted	Part 1: Mild Renal Impairment (RI)	Part 1: Moderate Renal Impairment	Part 1: Healthy Participants (Mild + Moderate RI)	Part 1: Severe Renal Impairment	Part 1: Healthy Participants (Severe RI)
Part 1: Fraction of MK-3866 Excretion (Urine) During Each Collection Interval (Fe0-24)	0.485 (0.398 to 0.592)	0.346 (0.242 to 0.494)	0.537 (0.445 to 0.648)	0.173 (0.114 to 0.263)	0.575 (0.482 to 0.686)

Statistical analysis

Part 1: Mild Renal Impairment (RI) vs Part 1: Healthy Participants (Mild + Moderate RI) · Geometric least squares mean ratio (gmr): 0.90 · 90% CI 0.74 to 1.11GMR is ratio of Experimental Group / Healthy Group
Part 1: Moderate Renal Impairment vs Part 1: Healthy Participants (Mild + Moderate RI) · Geometric least squares mean ratio (gmr): 0.64 · 90% CI 0.47 to 0.88GMR is ratio of Experimental Group / Healthy Group
Part 1: Severe Renal Impairment vs Part 1: Healthy Participants (Severe RI) · Geometric least squares mean ratio (gmr): 0.30 · 90% CI 0.21 to 0.43GMR is ratio of Experimental Group / Healthy Group

SecondaryPart 2: Total Amount of MK-3866 Excreted Unchanged in the Urine Over the Period of 24 Hours (Ae0-24)

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
Reported as:: Geometric mean · mg

Part 2: Total Amount of MK-3866 Excreted Unchanged in the Urine Over the Period of 24 Hours (Ae0-24)
mg	Part 2, Period 1: ESRD Undergoing HD (Dosed After HD)	Part 2, Period 2: ESRD Undergoing HD (Dosed Before HD)	Part 1: Healthy Participants (ESRD)
Part 2: Total Amount of MK-3866 Excreted Unchanged in the Urine Over the Period of 24 Hours (Ae0-24)	4.31 ± 42.6	2.21 ± 4.4	115 ± 24.9

SecondaryPart 2: Renal Clearance (CLr) of MK-3866

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
Reported as:: Geometric mean · L/hr

Part 2: Renal Clearance (CLr) of MK-3866
L/hr	Part 2, Period 1: ESRD Undergoing HD (Dosed After HD)	Part 2, Period 2: ESRD Undergoing HD (Dosed Before HD)	Part 1: Healthy Participants (ESRD)
Part 2: Renal Clearance (CLr) of MK-3866	0.0474 ± 8.5	0.0558 ± 15.8	2.92 ± 32.1

SecondaryPart 2: Fraction of MK-3866 Excretion (Urine) During Each Collection Interval (Fe0-24)

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
Reported as:: Geometric mean · Fraction of MK-3866 Excreted

Part 2: Fraction of MK-3866 Excretion (Urine) During Each Collection Interval (Fe0-24)
Fraction of MK-3866 Excreted	Part 2, Period 1: ESRD Undergoing HD (Dosed After HD)	Part 2, Period 2: ESRD Undergoing HD (Dosed Before HD)	Part 1: Healthy Participants (ESRD)
Part 2: Fraction of MK-3866 Excretion (Urine) During Each Collection Interval (Fe0-24)	0.0216 ± 42.6	0.0111 ± 4.4	0.574 ± 24.9

SecondaryPart 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
Reported as:: Geometric mean · µM

Part 2: Concentration of MK-3866 in Plasma Entering the Dialyzer Line (Ca)
µM	Part 2, Period 2: ESRD Undergoing HD (Dosed Before HD)
0.75 hours after dosing	17.6 ± 15.6
1 hour after dosing	12.0 ± 35.8
1.5 hours after dosing	8.67 ± 33.1
2 hours after dosing	7.25 ± 10.8
2.5 hours after dosing	5.75 ± 8.5
3 hours after dosing	4.32 ± 35.8
3.5 hours after dosing	3.98 ± 10.3
4 hours after dosing	2.98 ± 31.8
4.5 hours after dosing	2.57 ± 31.0

SecondaryPart 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
Reported as:: Geometric mean · µM

Part 2: Concentration of MK-3866 in Plasma Exiting the Dialyzer Line (Cv)
µM	Part 2, Period 2: ESRD Undergoing HD (Dosed Before HD)
0.75 hours after dosing	8.32 ± 20.7
1 hour after dosing	7.16 ± 24.0
1.5 hours after dosing	5.17 ± 25.1
2 hours after dosing	3.71 ± 10.5
2.5 hours after dosing	2.92 ± 11.4
3 hours after dosing	2.69 ± 21.0
3.5 hours after dosing	2.12 ± 25.2
4 hours after dosing	2.10 ± 33.8
4.5 hours after dosing	1.66 ± 49.4

SecondaryPart 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
Reported as:: Geometric mean · µM*hr

Part 2: Area Under the Concentration-time Curve of MK-3866 in Plasma Entering the Dialyzer Line During the Dialysis Period (AUCD)
µM*hr	Part 2, Period 2: ESRD Undergoing HD (Dosed Before HD)
Part 2: Area Under the Concentration-time Curve of MK-3866 in Plasma Entering the Dialyzer Line During the Dialysis Period (AUCD)	29.4 ± 14.3

SecondaryPart 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
Reported as:: Geometric mean · µM*hr

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)
µM*hr	Part 2, Period 2: ESRD Undergoing HD (Dosed Before HD)
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 ± 19.0

SecondaryPart 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
Reported as:: Geometric mean · µM*hr

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)
µM*hr	Part 2, Period 2: ESRD Undergoing HD (Dosed Before HD)
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 ± 12.2

SecondaryPart 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
Reported as:: Geometric mean · L/hr

Part 2: Dialysis Clearance of MK-3866 Based on Plasma (CLD,Plasma)
L/hr	Part 2, Period 2: ESRD Undergoing HD (Dosed Before HD)
Part 2: Dialysis Clearance of MK-3866 Based on Plasma (CLD,Plasma)	4.81 ± 201.1

SecondaryPart 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
Reported as:: Mean · µM

Part 2: Concentration of MK-3866 in Dialysate Samples (CD)
µM	Part 2, Period 2: ESRD Undergoing HD (Dosed Before HD)
0.5 hours after dosing	1.07 ± 1.84
1 hour after dosing	3.02 ± 0.748
1.5 hours after dosing	2.29 ± 0.153
2 hours after dosing	1.62 ± 0.142
2.5 hours after dosing	1.30 ± 0.134
3 hours after dosing	1.08 ± 0.106
3.5 hours after dosing	0.894 ± 0.0896
4 hours after dosing	0.695 ± 0.114
4.5 hours after dosing	0.542 ± 0.251

SecondaryPart 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
Reported as:: Geometric mean · mg

Part 2: Amount of MK-3866 Recovered From Each Dialysate Sample (AD)
mg	Part 2, Period 2: ESRD Undergoing HD (Dosed Before HD)
0.5 hours after dosing	0.946 ± 8.6
1 hour after dosing	0.736 ± 31.8
1.5 hours after dosing	0.576 ± 6.8
2 hours after dosing	0.408 ± 8.7
2.5 hours after dosing	0.327 ± 10.7
3 hours after dosing	0.272 ± 10.3
3.5 hours after dosing	0.224 ± 10.3
4 hours after dosing	0.173 ± 17.2
4.5 hours after dosing	0.158 ± 13.7

SecondaryPart 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
Reported as:: Geometric mean · mg/hr

Part 2: Rate of Removal of MK-3866 From the Dialysate (rr)
mg/hr	Part 2, Period 2: ESRD Undergoing HD (Dosed Before HD)
0.5 hours after dosing	56.7 ± 8.6
1 hour after dosing	44.2 ± 31.8
1.5 hours after dosing	34.6 ± 6.8
2 hours after dosing	24.5 ± 8.7
2.5 hours after dosing	19.6 ± 10.7
3 hours after dosing	16.3 ± 10.3
3.5 hours after dosing	13.5 ± 10.3
4 hours after dosing	10.4 ± 17.2
4.5 hours after dosing	9.51 ± 13.7

SecondaryPart 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
Reported as:: Geometric mean · mg

Part 2: Cumulative Amount of MK-3866 Recovered From the Dialysate (AD,Total)
mg	Part 2, Period 2: ESRD Undergoing HD (Dosed Before HD)
Part 2: Cumulative Amount of MK-3866 Recovered From the Dialysate (AD,Total)	89.0 ± 9.3

SecondaryPart 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
Reported as:: Geometric mean · L/hr

Part 2: Hemodialysis Clearance of MK-3866 Based on the Dialysate(CLD,Dialysate)
L/hr	Part 2, Period 2: ESRD Undergoing HD (Dosed Before HD)
Part 2: Hemodialysis Clearance of MK-3866 Based on the Dialysate(CLD,Dialysate)	6.01 ± 13.2

SecondaryNumber 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
Reported as:: Count of participants · Participants

Number of Participants With at Least One Adverse Event (AE)
Participants	Part 1: Mild Renal Impairment (RI)	Part 1: Moderate Renal Impairment	Part 1: Severe Renal Impairment	Part 2, Period 1: ESRD Undergoing HD (Dosed After HD)	Part 2, Period 2: ESRD Undergoing HD (Dosed Before HD)	Part 1: Healthy Participants
Number of Participants With at Least One Adverse Event (AE)	3	3	1	1	1	1

SecondaryNumber of Participants Discontinuing the Study Due to an Adverse Event

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
Reported as:: Count of participants · Participants

Number of Participants Discontinuing the Study Due to an Adverse Event
Participants	Part 1: Mild Renal Impairment (RI)	Part 1: Moderate Renal Impairment	Part 1: Severe Renal Impairment	Part 2, Period 1: ESRD Undergoing HD (Dosed After HD)	Part 2, Period 2: ESRD Undergoing HD (Dosed Before HD)	Part 1: Healthy Participants
Number of Participants Discontinuing the Study Due to an Adverse Event	0	0	0	1	1	0

Adverse events

Collected over 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. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Part 1: Mild Renal Impairment (RI)	0/8 (0%)	0/8 (0%)	3/8 (37.5%)
Part 1: Moderate Renal Impairment	0/8 (0%)	0/8 (0%)	3/8 (37.5%)
Part 1: Severe Renal Impairment	0/8 (0%)	0/8 (0%)	1/8 (12.5%)
Part 2, Period 1: ESRD Undergoing HD (Dosed After HD)	0/8 (0%)	1/8 (12.5%)	0/8 (0%)
Part 2, Period 2: ESRD Undergoing HD (Dosed Before HD)	0/7 (0%)	1/7 (14.3%)	0/7 (0%)
Part 1: Healthy Participants	0/10 (0%)	0/10 (0%)	1/10 (10%)

Most frequent serious events

Most frequent serious events
Event	Part 1: Mild Renal Impairment (RI)	Part 1: Moderate Renal Impairment	Part 1: Severe Renal Impairment	Part 2, Period 1: ESRD Undergoing HD (Dosed After HD)	Part 2, Period 2: ESRD Undergoing HD (Dosed Before HD)	Part 1: Healthy Participants
Thrombotic strokeNervous system disorders	0/8	0/8	0/8	0/8	1/7	0/10
Colitis ischaemicGastrointestinal disorders	0/8	0/8	0/8	1/8	0/7	0/10

Most frequent other events

Most frequent other events
Event	Part 1: Mild Renal Impairment (RI)	Part 1: Moderate Renal Impairment	Part 1: Severe Renal Impairment	Part 2, Period 1: ESRD Undergoing HD (Dosed After HD)	Part 2, Period 2: ESRD Undergoing HD (Dosed Before HD)	Part 1: Healthy Participants
HeadacheNervous system disorders	0/8	2/8	0/8	0/8	0/7	0/10
Abdominal painGastrointestinal disorders	1/8	0/8	0/8	0/8	0/7	0/10
FlatulenceGastrointestinal disorders	0/8	0/8	1/8	0/8	0/7	0/10
DysuriaRenal and urinary disorders	1/8	0/8	0/8	0/8	0/7	0/10
Drug eruptionSkin and subcutaneous tissue disorders	1/8	0/8	0/8	0/8	0/7	0/10
Upper respiratory tract infectionInfections and infestations	0/8	1/8	0/8	0/8	0/7	0/10
DysgeusiaNervous system disorders	0/8	0/8	0/8	0/8	0/7	1/10

Baseline characteristics

Age, Continuous
Age, Continuous(Years)	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
Mean	68.3 ± 5.65	67.0 ± 9.24	57.3 ± 13.83	61.2 ± 8.36	51.9 ± 8.68	61.1 ± 10.83

Sex: Female, Male
Sex: Female, Male(Participants)	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
Female	4	2	2	4	3	15
Male	4	6	6	6	5	27

Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)	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
Hispanic or Latino	2	4	4	4	1	15
Not Hispanic or Latino	6	4	4	6	7	27
Unknown or Not Reported	0	0	0	0	0	0

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	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
American Indian or Alaska Native	0	0	0	0	0	0
Asian	0	1	0	0	0	1
Native Hawaiian or Other Pacific Islander	0	0	0	0	0	0
Black or African American	2	1	3	2	7	15
White	6	6	5	8	1	26
More than one race	0	0	0	0	0	0
Unknown or Not Reported	0	0	0	0	0	0

Body Mass Index
Body Mass Index(kg/m^2)	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
Mean	28.125 (20.00 to 36.00)	27.625 (23.00 to 34.00)	28.625 (20.00 to 32.00)	28.800 (27.00 to 30.00)	29.875 (27.00 to 34.00)	28.619 (20.00 to 36.00)

Study locations

2 sites

Clinical Pharmacology of Miami ( Site 0001)
Hialeah, Florida 33014, United States
Orlando Clinical Research Center ( Site 0002)
Orlando, Florida 32809, United States

References and documents

Study documents

Protocol and statistical analysis plan · Aug 3, 2017

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Data sharing details ↗ · engagezone.msd.com

Timeline

Tracking since Sep 25, 2026

ElapsedEstimatedEstimated, not yet reachedSimilar studies: half by the dot; the band is the middle halfHalf of similar studies reached it by the dot; the band is the middle half, from a quarter to three quarters

Ran from Sep 2017 to primary completion in Jan 2018, 4 months.

Results were first posted in Apr 2019, 1 year 2 months after primary completion.

Of 248 industry-sponsored phase 1 interventional studies under Renal Insufficiency, half reached primary completion within 8 months of starting (the median), counting those still running; a quarter within 4 and three quarters within 14. This study's 4 months is below that.

Counting every sponsor, half of 270 studies reached it within 8 months; a quarter within 5 and three quarters within 15.

How these figures are worked out, and which studies are left out of them.

Registered: Aug 21, 2017
First posted: Aug 23, 2017
StartActual: Sep 1, 2017
Primary completionActual: Jan 28, 2018
CompletionActual: Feb 9, 2018
Results first posted: Apr 19, 2019
Last update: Apr 19, 2019

What these dates mean

Start.: When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.: When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.: When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.: Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.

No changes since tracking began. The registry record was last updated on Apr 19, 2019, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT03259087
Lead sponsor: Merck Sharp & Dohme LLC
Responsible party: Sponsor
First posted: Aug 23, 2017
Start date: Sep 1, 2017
Primary completion: Jan 28, 2018
Completion: Feb 9, 2018
Results posted: Apr 19, 2019
Last update: Apr 19, 2019

Study contacts

Medical Director

study director · Merck Sharp & Dohme LLC

Oversight

Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

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Pharmacokinetics (PK) and Safety of a Single Intravenous (IV) Dose of MK-3866 in Participants With Impaired Renal Function and in Healthy Controls (MK-3866-005)

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