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MK-6183

Phase 1

Healthy Volunteers | Small molecule | Nephrology |Merck & Company, Inc.|Last Updated: Feb 18, 2019

Success Probability

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Market & Valuation

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Trial Design

CONTROLLED
Total Trials1
Total Enrollment40

FDA Designations

No designations recorded

Clinical trial landscape

MK-6183 · 1 trial · 2 indications

Phase 1 1
NCT02341599Study of Pharmacokinetics of a Single IV Dose of CB-238,618 in Subjects With Varying Degrees of Renal Impairment Compared to Healthy Subjects (MK-6183-001)Healthy Volunteers
COMPLETED40 Analytics
PHASE1COMPLETED
Study of Pharmacokinetics of a Single IV Dose of CB-238,618 in Subjects With Varying Degrees of Renal Impairment Compared to Healthy Subjects (MK-6183-001)
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Study Endpoints

Primary Endpoints

Area Under the Plasma Concentration-time Curve (AUC) From Dosing to Last Measurable Concentration (AUC0-last) of MK-6183
Groups A to D & Group E: Period 2: Pre-dose and 0.5, 1 (end of infusion; EOI), 1.5, 2, 3, 6, 12, 24, 48, and 72 hours post-dose

AUC0-last is the area under the plasma concentration-time curve from the time of dosing to the last post-dose measurable concentration. Blood samples for Group E were collected both prior to and during HD (Period 1) and after HD (Period 2) \[data from Periods 1 and 2 were analyzed separately\]. In Period 1, HD commenced 3.5 hours post-dose (HD duration was 3.5 to 4 hours) and sample collection continued until 48 hours post-dose. The specific time frame of plasma sample collection for Group E: Period 1 was pre-dose, 0.5 hours post-dose, EOI, 1.5 hours post-dose, 2 hours post-dose, 3 hours post-dose (pre-HD), 3.5 hours post-dose with HD, 5 hours post-dose with HD, pre-end of HD, 30 min post-HD, 1 hour post-HD, 2 hours post-HD, 12 hours post-dose, 24 hours post-dose, and 48 hours post-dose.

AUC From Dosing to ∞ (AUC0-∞) of MK-6183
Groups A to D & Group E: Period 2: Pre-dose and 0.5, EOI, 1.5, 2, 3, 6, 12, 24, 48, and 72 hours post-dose

AUC0-∞ is the extrapolated area under the plasma concentration-time curve from the time of dosing to infinity. Blood samples for Group E were collected both prior to and during HD (Period 1) and after HD (Period 2) \[data from Periods 1 and 2 were analyzed separately\]. In Period 1, HD commenced 3.5 hours post-dose (HD duration was 3.5 to 4 hours) and sample collection continued until 48 hours post-dose. The specific time frame of plasma sample collection for Group E: Period 1 was pre-dose, 0.5 hours post-dose, EOI, 1.5 hours post-dose, 2 hours post-dose, 3 hours post-dose (pre-HD), 3.5 hours post-dose with HD, 5 hours post-dose with HD, pre-end of HD, 30 min post-HD, 1 hour post-HD, 2 hours post-HD, 12 hours post-dose, 24 hours post-dose, and 48 hours post-dose. For statistical analyses, Group A is the reference and least squares (LS) mean ratios for tests (Groups B to E) are calculated as test/reference; Group E: Period 1 and Group E: Period 2 were also compared.

Maximum Plasma Drug Concentration (Cmax) of MK-6183
Groups A to D & Group E: Period 2: Pre-dose and 0.5, EOI, 1.5, 2, 3, 6, 12, 24, 48, and 72 hours post-dose

Cmax is the maximum observed post-dose drug concentration in plasma. Blood samples for Group E were collected both prior to and during HD (Period 1) and after HD (Period 2) \[data from Periods 1 and 2 were analyzed separately\]. In Period 1, HD commenced 3.5 hours post-dose (HD duration was 3.5 to 4 hours) and sample collection continued until 48 hours post-dose. The specific time frame of sample collection for Group E: Period 1 was pre-dose, 0.5 hours post-dose, EOI, 1.5 hours post-dose, 2 hours post-dose, 3 hours post-dose (pre-HD), 3.5 hours post-dose with HD, 5 hours post-dose with HD, pre-end of HD, 30 min post-HD, 1 hour post-HD, 2 hours post-HD, 12 hours post-dose, 24 hours post-dose, and 48 hours post-dose. For statistical analyses, Group A is the reference and LS mean ratios for tests (Groups B to E) are calculated as test/reference; Group E: Period 1 and Group E: Period 2 were also compared.

Apparent Total Body Clearance of MK-6183 From Plasma (CL)
Groups A to D & Group E: Period 2: Pre-dose and 0.5, EOI, 1.5, 2, 3, 6, 12, 24, 48, and 72 hours post-dose

CL is a measure of the clearance of drug from plasma via metabolism and excretion. Blood samples for Group E were collected both prior to and during HD (Period 1) and after HD (Period 2) \[data from Periods 1 and 2 were analyzed separately\]. In Period 1, HD commenced 3.5 hours post-dose (HD duration was 3.5 to 4 hours) and sample collection continued until 48 hours post-dose. The specific time frame of plasma sample collection for Group E: Period 1 was pre-dose, 0.5 hours post-dose, EOI, 1.5 hours post-dose, 2 hours post-dose, 3 hours post-dose (pre-HD), 3.5 hours post-dose with HD, 5 hours post-dose with HD, pre-end of HD, 30 min post-HD, 1 hour post-HD, 2 hours post-HD, 12 hours post-dose, 24 hours post-dose, and 48 hours post-dose.

Volume of Distribution at Steady State (Vss) of MK-6183
Groups A to D & Group E: Period 2: Pre-dose and 0.5, EOI, 1.5, 2, 3, 6, 12, 24, 48, and 72 hours post-dose

Vss is the apparent volume of distribution at steady state for MK-6183. Blood samples for Group E were collected both prior to and during HD (Period 1) and after HD (Period 2) \[data from Periods 1 and 2 were analyzed separately\]. In Period 1, HD commenced 3.5 hours post-dose (HD duration was 3.5 to 4 hours) and sample collection continued until 48 hours post-dose. The specific time frame of sample collection for Group E: Period 1 was pre-dose, 0.5 hours post-dose, EOI, 1.5 hours post-dose, 2 hours post-dose, 3 hours post-dose (pre-HD), 3.5 hours post-dose with HD, 5 hours post-dose with HD, pre-end of HD, 30 min post-HD, 1 hour post-HD, 2 hours post-HD, 12 hours post-dose, 24 hours post-dose, and 48 hours post-dose.

Apparent Plasma Half-life (t½) of MK-6183
Groups A to D & Group E: Period 2: Pre-dose and 0.5, EOI, 1.5, 2, 3, 6, 12, 24, 48, and 72 hours post-dose

t½ is the amount of time required for the plasma concentration of MK-6183 to reduce by 50%. Blood samples for Group E were collected both prior to and during HD (Period 1) and after HD (Period 2) \[data from Periods 1 and 2 were analyzed separately\]. In Period 1, HD commenced 3.5 hours post-dose (HD duration was 3.5 to 4 hours) and sample collection continued until 48 hours post-dose. The specific time frame of sample collection for Group E: Period 1 was pre-dose, 0.5 hours post-dose, EOI, 1.5 hours post-dose, 2 hours post-dose, 3 hours post-dose (pre-HD), 3.5 hours post-dose with HD, 5 hours post-dose with HD, pre-end of HD, 30 min post-HD, 1 hour post-HD, 2 hours post-HD, 12 hours post-dose, 24 hours post-dose, and 48 hours post-dose.

Cumulative Amount of MK-6183 Excreted in Urine or Dialysate (Ae)
Groups A to D (urine): 0 to 24, 24 to 48, and 48 to 72 hours post-dose; Group E (dialysate): 0 to 1, 1 to 2, 2 to 3, and 3 to 4 hours after starting HD

Ae is the cumulative amount of drug excreted unchanged in urine or dialysate. For Groups A, B, C, and D, Ae was assessed in urine. For Group E: Period 1, Ae was assessed in dialysate (participants in Group E had no detectable urine data) at hourly collection intervals during HD (HD commenced 3 hours after dosing).

Renal Clearance of MK-6183 (CLr)
0 to 24, 24 to 48, and 48 to 72 hours post-dose

CLr is the clearance of drug from plasma via the kidneys. Only data from Groups A, B, C, and D is presented; participants in Group E (Period 1) had no detectable urine data. Data for Group E: Period 1 are presented below in the dialysate clearance measure.

Dialysate Clearance of MK-6183 (CLd)
0 to 1, 1 to 2, 2 to 3, and 3 to 4 hours after starting HD

CLd is the amount of drug cleared from plasma via dialysis. Only data collected during HD (Group E: Period 1) is presented (HD commenced 3 hours after dosing).

Fraction of the Administered Dose of MK-6183 Excreted Unchanged in Urine or Dialysate (Fe)
Groups A to D (urine): 0 to 24, 24 to 48, and 48 to 72 hours post-dose; Group E (dialysate): 0 to 1, 1 to 2, 2 to 3, and 3 to 4 hours after starting HD

Fe is the fraction (percentage) of the administered dose that was excreted unchanged in urine (Groups A to D) or dialysate (Group E: Period 1; HD commenced 3 hours after dosing).

Secondary Endpoints

Number of Participants Experiencing an Adverse Event (AE)
Up to 12 days
Number of Participants Discontinuing From the Study Due to an AE
Up to 12 days
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Study Design & Arms

AllocationNON_RANDOMIZED
MaskingNONE
ModelPARALLEL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
Group A: HealthyEXPERIMENTALHealthy participants with normal renal function (Stage 1: eGFR ≥90 mL/min/1.73m\^2).
Group B: Mild RIEXPERIMENTALParticipants with mild RI (Stage 2: eGFR ≥60 to \<90 mL/min/1.73m\^2).
Group C: Moderate RIEXPERIMENTALParticipants with moderate RI (Stage 3: eGFR ≥30 to \<60 mL/min/1.73m\^2).
Group D: Severe RIEXPERIMENTALParticipants with severe RI (Stage 4: eGFR \<30 mL/min/1.73m\^2) not receiving HD.
Group E: ESRD-HDEXPERIMENTALParticipants with ESRD who are receiving HD for at least 3 months preceding the initial dose in this study (Stage 5).

Interventions

NameTypeDescription
MK-6183DRUGMK-6183 (CB-238,614) is supplied as lyophilized powder 500 mg vial and mixed into solution for 100 mL intravenous (IV) administration over 1 hour.
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Eligibility Criteria

Age Range18 Years to N/A
SexALL
Healthy VolunteersYes

Inclusion Criteria: * Participants who are healthy; or who have mild, moderate, or severe RI; or who have ESRD requiring HD. Participants with ESRD requiring HD should have been receiving HD 3 times per week for at least 3 months preceding the initial dose in this study Exclusion Criteria: * For ...

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Frequently asked questions about MK-6183

What is MK-6183 used for?

MK-6183 is an investigational small molecule being studied in healthy volunteers and subjects with renal impairment. It is being developed by Merck & Company, Inc. (MRK) in the therapeutic area of nephrology. The drug is currently in Phase 1 clinical development.

Who makes MK-6183?

MK-6183 is being developed by Merck & Company, Inc., which trades under the ticker symbol MRK. The company is conducting clinical trials to evaluate the drug's pharmacokinetics in subjects with varying degrees of renal impairment compared to healthy subjects.

What phase is MK-6183 in?

MK-6183 is in Phase 1 clinical development. It is an investigational drug and has not been approved by regulatory authorities. A single Phase 1 trial has been completed, with no active trials currently ongoing.

What clinical trials is MK-6183 in?

MK-6183 has one completed clinical trial, NCT02341599, titled 'Study of Pharmacokinetics of a Single IV Dose of CB-238,618 in Subjects With Varying Degrees of Renal Impairment Compared to Healthy Subjects (MK-6183-001)'. This Phase 1 study enrolled 40 participants and was a controlled trial.

Is MK-6183 the same as CB-238,618?

Yes, MK-6183 is also known as CB-238,618. The clinical trial NCT02341599 refers to the drug as CB-238,618, while the sponsor name is MK-6183. Both names refer to the same investigational compound being developed by Merck & Company, Inc.