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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)

Primary Purpose

Renal Impairment

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

MK-3866

About this trial

This is an interventional treatment trial for Renal Impairment

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

Females of non-childbearing potential. Male participants with female partner(s) of child-bearing potential agree to use a medically acceptable method of contraception during the study and for 90 days after dosing. If partner is pregnant, males agree to use a condom; if partner is of child-bearing potential, partner must use additional birth control
Male participants agree not to donate sperm from the first dose until 90 days after dosing
Adequate venous access

Renal Impaired Participants

Liver function tests (serum alanine aminotransferase [ALT] and aspartate aminotransferase [AST]) and serum bilirubin (total and direct) within upper limit of normal
Panels A, B, and C: no clinically significant change in renal status at least 1 month prior to dosing and not currently or previously been on hemodialysis
Panel E only: ESRD maintained on stable regimen of at least 3 times per week HD for at least 3 months prior to first dosing

Healthy Participants

Age within ± 15 years of the mean age of participants with impaired renal function to which the healthy participant is matched
Medically healthy as per medical history, physical examination, vital signs, 12-lead electrocardiograms (ECGs), and clinical laboratory safety tests
Blood urea nitrogen, liver function tests (ALT, AST, alkaline phosphatase [ALP]), and serum bilirubin (total and direct) within upper limit of normal.

Exclusion Criteria:

Mentally/legally incapacitated, or significant emotional problems or significant psychiatric disorder
History of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological, respiratory, genitourinary or major neurological abnormalities or diseases
History of any illness that might confound the results of the study or poses an additional risk to the participant by their participation in the study
Clinically significant history of cancer
Smoker and/or has used nicotine or nicotine-containing products within 3 months prior to screening
Female participants of childbearing potential, pregnant, or lactating
Positive results for urine or saliva drug screen and/or urine or breath alcohol screen at screening or check-in
Positive results at screening for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV)
Consumes more than 3 glasses of alcoholic beverages within 6 months of screening
Consumes excessive amounts of coffee, tea, cola, energy-drinks, or other caffeinated beverages per day
Major surgery, donated or lost 1 unit of blood within 4 weeks prior to screening, or donated plasma within 7 days prior to dosing in Part 1 or first dose in Part 2

Renal Impaired Participants

Panels A, B, and C: Failed renal transplant or has had nephrectomy
Panels A, B, and C: Rapidly fluctuating renal function, as determined by historical measurements; or demonstrated/suspected renal artery stenosis
Panel E only: Has required frequent emergent HD (≥3) within a year prior to first dosing

Healthy Participants

Renal transplant or nephrectomy

Sites / Locations

Clinical Pharmacology of Miami ( Site 0001)
Orlando Clinical Research Center ( Site 0002)

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Arm Label

Part 1: Mild Renal Impairment

Part 1: Moderate Renal Impairment

Part 1: Severe Renal Impairment

Part 1: Healthy Participants

Part 2: End-stage Renal Disease Undergoing Hemodialysis

Arm Description

Participants receive a single IV infusion of 200 mg MK-3866 over 30 minutes on Day 1.

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.

Outcomes

Primary Outcome Measures

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).

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.

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.

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.

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.

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.

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.

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).

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Secondary Outcome Measures

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.

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.

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.

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

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

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

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Number of Participants Discontinuing the Study Due to an Adverse Event

Full Information

NCT ID

NCT03259087

First Posted

August 21, 2017

Last Updated

January 25, 2019

Sponsor

Merck Sharp & Dohme LLC

1. Study Identification

Unique Protocol Identification Number

NCT03259087

Brief Title

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)

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

Study Type

Interventional

2. Study Status

Record Verification Date

January 2019

Overall Recruitment Status

Completed

Study Start Date

September 1, 2017 (Actual)

Primary Completion Date

January 28, 2018 (Actual)

Study Completion Date

February 9, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Merck Sharp & Dohme LLC

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

The purpose of this study is to compare plasma and urine PK parameters of MK-3866 between participants with impaired renal function and healthy control participants, to investigate the extent to which MK-3866 is removed from the plasma by hemodialysis (HD), and evaluate the safety and tolerability of MK-3866 in participants with impaired renal function.

Detailed Description

This is an open-label, 2-part single dose study: Part 1 will include participants with mild, moderate, and severe renal impairment (as well as healthy control participants), and Part 2 will include participants with end stage renal disease (ESRD) undergoing HD. Participants in Part 1 will receive a single IV dose of MK-3866, and plasma and urine samples will be collected over pre-specified time intervals. Participants in Part 2 will receive a single IV dose of MK-3866 on two separate occasions: in Period 1 immediately following their normally-scheduled HD, and in Period 2 approximately 30 minutes prior to their normally-scheduled HD. Plasma, urine, and dialysate samples will be collected over pre-specified time intervals for Part 2.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Renal Impairment

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

42 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Part 1: Mild Renal Impairment

Arm Type

Experimental

Arm Description

Participants receive a single IV infusion of 200 mg MK-3866 over 30 minutes on Day 1.

Arm Title

Part 1: Moderate Renal Impairment

Arm Type

Experimental

Arm Description

Participants receive a single IV infusion of 200 mg MK-3866 over 30 minutes on Day 1.

Arm Title

Part 1: Severe Renal Impairment

Arm Type

Experimental

Arm Description

Participants receive a single IV infusion of 200 mg MK-3866 over 30 minutes on Day 1.

Arm Title

Part 1: Healthy Participants

Arm Type

Experimental

Arm Description

Participants receive a single IV infusion of 200 mg MK-3866 over 30 minutes on Day 1.

Arm Title

Part 2: End-stage Renal Disease Undergoing Hemodialysis

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

MK-3866

Intervention Description

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

Primary Outcome Measure Information:

Title

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

Description

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

Title

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)

Description

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

Title

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

Description

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

Title

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

Description

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

Title

Part 1: Maximum Plasma Concentration of MK-3866 (Cmax)

Description

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

Title

Part 1: Plasma Clearance of MK-3866 (CL)

Description

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

Title

Part 1: Time to Maximum Plasma Concentration of MK-3866 (Tmax)

Description

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

Title

Part 1: Elimination Terminal Half-life of Plasma MK-3866 (t1/2)

Description

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

Title

Part 1: Volume of Distribution of Plasma MK-3866 (Vz)

Description

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

Title

Part 2: AUC0-inf of Plasma MK-3866

Description

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

Title

Part 2: AUC0-last of Plasma MK-3866

Description

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

Title

Part 2: AUC0-24 of Plasma MK-3866

Description

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

Title

Part 2: Ceoi of Plasma MK-3866

Description

Time Frame

At the end of the infusion (0.5 hours after infusion start) on Day 1 of Period 1 and Period 2

Title

Part 2: Cmax of Plasma MK-3866

Description

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

Title

Part 2: CL of Plasma MK-3866

Description

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

Title

Part 2: Tmax of Plasma MK-3866

Description

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

Title

Part 2: t1/2 of Plasma MK-3866

Description

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

Title

Part 2: Vz of Plasma MK-3866

Description

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 Outcome Measure Information:

Title

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

Description

Time Frame

Predose and 0-4, 4-8, 8-12, and 12-24 hours after dosing on Day 1

Title

Part 1: Renal Clearance (CLr) of MK-3866

Description

Time Frame

Predose and 0-4, 4-8, 8-12, and 12-24 hours after dosing on Day 1

Title

Part 1: Fraction of MK-3866 Excretion (Urine) During Each Collection Interval (Fe0-24)

Description

Time Frame

Predose and 0-4, 4-8, 8-12, and 12-24 hours after dosing on Day 1

Title

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

Description

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

Title

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

Description

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

Title

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

Description

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

Title

Part 2: Concentration of MK-3866 in Plasma Entering the Dialyzer Line (Ca)

Description

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

Title

Part 2: Concentration of MK-3866 in Plasma Exiting the Dialyzer Line (Cv)

Description

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

Title

Part 2: Area Under the Concentration-time Curve of MK-3866 in Plasma Entering the Dialyzer Line During the Dialysis Period (AUCD)

Description

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

Title

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)

Description

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

Title

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)

Description

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

Title

Part 2: Dialysis Clearance of MK-3866 Based on Plasma (CLD,Plasma)

Description

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

Title

Part 2: Concentration of MK-3866 in Dialysate Samples (CD)

Description

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

Title

Part 2: Amount of MK-3866 Recovered From Each Dialysate Sample (AD)

Description

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

Title

Part 2: Rate of Removal of MK-3866 From the Dialysate (rr)

Description

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

Title

Part 2: Cumulative Amount of MK-3866 Recovered From the Dialysate (AD,Total)

Description

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

Title

Part 2: Hemodialysis Clearance of MK-3866 Based on the Dialysate(CLD,Dialysate)

Description

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

Title

Number of Participants With at Least One Adverse Event (AE)

Description

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

Title

Number of Participants Discontinuing the Study Due to an Adverse Event

Description

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Females of non-childbearing potential. Male participants with female partner(s) of child-bearing potential agree to use a medically acceptable method of contraception during the study and for 90 days after dosing. If partner is pregnant, males agree to use a condom; if partner is of child-bearing potential, partner must use additional birth control Male participants agree not to donate sperm from the first dose until 90 days after dosing Adequate venous access Renal Impaired Participants Liver function tests (serum alanine aminotransferase [ALT] and aspartate aminotransferase [AST]) and serum bilirubin (total and direct) within upper limit of normal Panels A, B, and C: no clinically significant change in renal status at least 1 month prior to dosing and not currently or previously been on hemodialysis Panel E only: ESRD maintained on stable regimen of at least 3 times per week HD for at least 3 months prior to first dosing Healthy Participants Age within ± 15 years of the mean age of participants with impaired renal function to which the healthy participant is matched Medically healthy as per medical history, physical examination, vital signs, 12-lead electrocardiograms (ECGs), and clinical laboratory safety tests Blood urea nitrogen, liver function tests (ALT, AST, alkaline phosphatase [ALP]), and serum bilirubin (total and direct) within upper limit of normal. Exclusion Criteria: Mentally/legally incapacitated, or significant emotional problems or significant psychiatric disorder History of clinically significant endocrine, gastrointestinal, cardiovascular, hematological, hepatic, immunological, respiratory, genitourinary or major neurological abnormalities or diseases History of any illness that might confound the results of the study or poses an additional risk to the participant by their participation in the study Clinically significant history of cancer Smoker and/or has used nicotine or nicotine-containing products within 3 months prior to screening Female participants of childbearing potential, pregnant, or lactating Positive results for urine or saliva drug screen and/or urine or breath alcohol screen at screening or check-in Positive results at screening for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV) Consumes more than 3 glasses of alcoholic beverages within 6 months of screening Consumes excessive amounts of coffee, tea, cola, energy-drinks, or other caffeinated beverages per day Major surgery, donated or lost 1 unit of blood within 4 weeks prior to screening, or donated plasma within 7 days prior to dosing in Part 1 or first dose in Part 2 Renal Impaired Participants Panels A, B, and C: Failed renal transplant or has had nephrectomy Panels A, B, and C: Rapidly fluctuating renal function, as determined by historical measurements; or demonstrated/suspected renal artery stenosis Panel E only: Has required frequent emergent HD (≥3) within a year prior to first dosing Healthy Participants Renal transplant or nephrectomy

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Medical Director

Organizational Affiliation

Merck Sharp & Dohme LLC

Official's Role

Study Director

Facility Information:

Facility Name

Clinical Pharmacology of Miami ( Site 0001)

City

Hialeah

State/Province

Florida

ZIP/Postal Code

33014

Country

United States

Facility Name

Orlando Clinical Research Center ( Site 0002)

City

Orlando

State/Province

Florida

ZIP/Postal Code

32809

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

IPD Sharing URL

http://engagezone.msd.com/ds_documentation.php

Learn more about this trial

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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