Renal ImpairmentPhase 1NCT03259087

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 study testing MK-3866 in people with Renal Impairment, run by Merck Sharp & Dohme LLC at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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… Read more about this study

Who is it for?: Ages 18 to 75 yearsHealthy volunteers can take part
Conditions the study is for: Renal Impairment
What is being tested?: MK-3866
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 42 participants
Where: 2 sitesUnited States
Study dates: 1 Sep 2017to 9 Feb 2018
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 75 years
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

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

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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.

Who cannot join

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

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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

Trial locations and contacts

2 sites in 1 country.

United States2 sites

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

Other trials in United States

About this study

Official title: A 2-Part, Open-Label Trial to Evaluate the Pharmacokinetics of MK-3866 Following the Administration of a Single IV Dose to Subjects With Mild, Moderate, and Severe Renal Impairment and End Stage Renal Disease

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: Renal Impairment
Being tested: MK-3866
Medical subject headings: Renal Insufficiency

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

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

Study groups in NCT03259087
Study group	Role	What they receive
Part 1: Mild Renal Impairment	Experimental	Participants receive a single IV infusion of 200 mg MK-3866 over 30 minutes on Day 1. Receives: Drug: MK-3866
Part 1: Moderate Renal Impairment	Experimental	Participants receive a single IV infusion of 200 mg MK-3866 over 30 minutes on Day 1. Receives: Drug: MK-3866
Part 1: Severe Renal Impairment	Experimental	Participants receive a single IV infusion of 200 mg MK-3866 over 30 minutes on Day 1. Receives: Drug: MK-3866
Part 1: Healthy Participants	Experimental	Participants receive a single IV infusion of 200 mg MK-3866 over 30 minutes on Day 1. Receives: Drug: MK-3866
Part 2: End-stage Renal Disease Undergoing Hemodialysis	Experimental	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. Receives: Drug: MK-3866

What is being measured

The primary outcome is the main question the study is designed to answer.

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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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 (19)

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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1 Sep 20179 Feb 2018

First posted23 Aug 2017
Study start1 Sep 2017
Primary completion28 Jan 2018
Study completion9 Feb 2018

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Renal ImpairmentStudies of the same condition, open and under way.
More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 42 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03259087
Sponsor's protocol ID: 3866-005
Other IDs: CA22640, MK-3866-005
Status last verified: Jan 2019
First submitted: 21 Aug 2017
Last updated: 19 Apr 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

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Questions to ask the study team

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Could I receive a placebo instead of the treatment?
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What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 19 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A 2-Part, Open-Label Trial to Evaluate the Pharmacokinetics of MK-3866 Following the Administration of a Single IV Dose to Subjects With Mild, Moderate, and Severe Renal Impairment and End Stage Renal Disease
ClinicalTrials.gov ID: NCT03259087
Acronym / sponsor ID: 3866-005
Conditions: Renal Impairment
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 42 participants (actual)
Lead sponsor: Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
Study start: 1 Sep 2017 (actual)
Primary completion: 28 Jan 2018 (actual)
Study completion: 9 Feb 2018 (actual)
First posted: 23 Aug 2017 (actual)
Results: Posted 19 Apr 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 5

Arm	Type	Receives
Part 1: Mild Renal Impairment	Experimental	Drug: MK-3866Participants receive a single IV infusion of 200 mg MK-3866 over 30 minutes on Day 1.
Part 1: Moderate Renal Impairment	Experimental	Drug: MK-3866Participants receive a single IV infusion of 200 mg MK-3866 over 30 minutes on Day 1.
Part 1: Severe Renal Impairment	Experimental	Drug: MK-3866Participants receive a single IV infusion of 200 mg MK-3866 over 30 minutes on Day 1.
Part 1: Healthy Participants	Experimental	Drug: MK-3866Participants receive a single IV infusion of 200 mg MK-3866 over 30 minutes on Day 1.
Part 2: End-stage Renal Disease Undergoing Hemodialysis	Experimental	Drug: MK-3866End-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.

Who may qualify

Ages: 18 to 75 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (11 listed)

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

Key exclusion criteria (17 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
MK-3866Single IV infusion of 200 mg administered over 30 minutes (±5 minutes) on Day 1 of each treatment period.	Drug	Part 1: Healthy Participants, Part 1: Mild Renal Impairment, Part 1: Moderate Renal Impairment, Part 1: Severe Renal Impairment, Part 2: End-stage Renal Disease Undergoing Hemodialysis

Primary outcome

Part 1: Area Under the Plasma Concentration-time Curve of MK-3866 From Time Zero to Infinity (AUC0-inf)
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
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)
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
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)
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
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)
Time frame: 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)
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
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)
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
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)
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
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)
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
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)
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
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
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
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
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
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
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
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
Time frame: 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
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
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
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
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
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
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
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
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
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
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.

19 secondary outcomes

Part 1: Total Amount of MK-3866 Excreted in the Urine Over 24 Hours (Ae0-24)
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
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)
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)
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
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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
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 and safety

Results posted to the registry on 19 Apr 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Part 1: Mild Renal Impairment (RI)	8	8
Part 1: Moderate Renal Impairment	8	8
Part 1: Severe Renal Impairment	8	8
Part 1: Healthy Participants	10	10
Part 2: End-stage Renal Disease Undergoing Hemodialysis	8	7

Primary outcome: Part 1: Area Under the Plasma Concentration-time Curve of MK-3866 From Time Zero to Infinity (AUC0-inf)

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. Geometric least squares mean (95% Confidence Interval). Unit: µM*hr

Measure	Part 1: Mild Renal Impairment (RI) n = 8	Part 1: Moderate Renal Impairment n = 8	Part 1: Healthy Participants (Mild + Moderate RI) n = 9	Part 1: Severe Renal Impairment n = 8	Part 1: Healthy Participants (Severe RI) n = 9
Value	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)

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 1.47)
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 2.02)
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 4.04)

Population analysed: 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).

Primary outcome: 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)

Measure	Part 1: Mild Renal Impairment (RI) n = 8	Part 1: Moderate Renal Impairment n = 8	Part 1: Healthy Participants (Mild + Moderate RI) n = 9	Part 1: Severe Renal Impairment n = 8	Part 1: Healthy Participants (Severe RI) n = 9
Value	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)

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 1.46)
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 1.99)
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 3.90)

Population analysed: 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).

Primary outcome: Part 1: Area Under the Plasma Concentration-time Curve of MK-3866 From Time Zero to 24 Hours After Dosing (AUC0-24)

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. Geometric least squares mean (95% Confidence Interval). Unit: µM*hr

Measure	Part 1: Mild Renal Impairment (RI) n = 8	Part 1: Moderate Renal Impairment n = 8	Part 1: Healthy Participants (Mild + Moderate RI) n = 9	Part 1: Severe Renal Impairment n = 8	Part 1: Healthy Participants (Severe RI) n = 9
Value	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)

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 1.40)
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 1.86)
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 2.97)

Population analysed: 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).

Primary outcome: Part 1: Plasma Concentration of MK-3866 at the End of the Infusion (Ceoi)

Time frame: At the end of the infusion (0.5 hours after infusion start) on Day 1. Geometric least squares mean (95% Confidence Interval). Unit: µM

Measure	Part 1: Mild Renal Impairment (RI) n = 8	Part 1: Moderate Renal Impairment n = 8	Part 1: Healthy Participants (Mild + Moderate RI) n = 9	Part 1: Severe Renal Impairment n = 8	Part 1: Healthy Participants (Severe RI) n = 9
Value	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)

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 1.16)
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 1.18)
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 1.29)

Population analysed: 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).

19 secondary outcomes are reported in the full results.

Adverse events

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. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Part 1: Mild Renal Impairment (RI)	0 of 8 (0%)	3 of 8 (37.5%)	0 of 8
Part 1: Moderate Renal Impairment	0 of 8 (0%)	3 of 8 (37.5%)	0 of 8
Part 1: Severe Renal Impairment	0 of 8 (0%)	1 of 8 (12.5%)	0 of 8
Part 2, Period 1: ESRD Undergoing HD (Dosed After HD)	1 of 8 (12.5%)	0 of 8 (0%)	0 of 8
Part 2, Period 2: ESRD Undergoing HD (Dosed Before HD)	1 of 7 (14.3%)	0 of 7 (0%)	0 of 7
Part 1: Healthy Participants	0 of 10 (0%)	1 of 10 (10%)	0 of 10

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 19 Apr 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: Yes. http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Medical Director study director

Merck Sharp & Dohme LLC

2 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing MK-3866 in people with Renal Impairment, run by Merck Sharp & Dohme LLC at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 Apr 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 19 Apr 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Part 1: Area Under the Plasma Concentration-time Curve of MK-3866 From Time Zero to Infinity (AUC0-inf) (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). The study lists 18 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03259087.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Apr 2019.