Healthy VolunteersPhase 1NCT02341599

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)

A Phase 1 study testing MK-6183 in people with Healthy Volunteers and Renal Impairment, run by Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA).

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 characterize the effect of renal function on the plasma, urine, and dialysate pharmacokinetic profile of MK-6183 (CB-238,618) in humans. The study will also assess the safety profile and tolerability of MK-6183 in healthy participants, participants with varying degrees of renal… Read more about this study

Who is it for?: Ages 18 years and olderHealthy volunteers can take part
Conditions the study is for: Healthy Volunteers, Renal Impairment
What is being tested?: MK-6183
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 40 participants
Where: No sites listed yet
Study dates: 11 Dec 2014to 20 Apr 2015
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 years and older
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

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

Who cannot join

For healthy participants (Group A): history or presence of any clinically significant illness (e.g., cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, oncologic, musculoskeletal, or psychiatric) or any other condition, including clinically significant anemia, which in the opinion of the investigator would jeopardize the safety of the participant or the validity of the study results
For participants with RI (Groups B to E): as above, except that RI and other medical conditions commonly associated with renal impairment (eg, hypertension, diabetes, which should be stable for at least three months preceding the initial dose of study medication in this study) are allowed
Clinically significant abnormalities on physical examination, medical history, 12-lead electrocardiogram (ECG), vital signs, or laboratory values, as judged by the investigator or designee. Subjects with renal impairment should have clinical laboratory values consistent with their disease and approved by the investigator
Evidence of clinically significant hepatic impairment including alanine aminotransferase or aspartate aminotransferase >1.5 × upper limit of normal (ULN) or bilirubin >1 × ULN
Hemoglobin <8 g/dL, unless considered stable and not clinically significant in the opinion of the investigator in subjects with ESRD and on HD
Participants with renal impairment who are not on a chronic stable drug regimen, defined as starting a new drug or changing dosage within 14 days prior to administration of study medication, except for drugs administered in relationship to HD
Participants with fluctuating or rapidly deteriorating renal function (assessment of the stability of the subject's renal function will be determined by the investigator)
Participant has a currently functioning renal transplant and/or has been on significant immunosuppressant therapy, as determined by the investigator, within the last 6 months

About this study

Official title: A Phase 1, Non-randomized, Parallel-group, Open-label Study to Characterize the Pharmacokinetics of a Single Intravenous Dose of CB-238,618 in Subjects With Varying Degrees of Renal Impairment Compared to Healthy Subjects

Conditions: Healthy Volunteers, Renal Impairment
Being tested: MK-6183
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-6183Drug
Also called CB-238,618
MK-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.

Study groups in NCT02341599
Study group	Role	What they receive
Group A: Healthy	Experimental	Healthy participants with normal renal function (Stage 1: eGFR ≥90 mL/min/1.73m^2). Receives: Drug: MK-6183
Group B: Mild RI	Experimental	Participants with mild RI (Stage 2: eGFR ≥60 to <90 mL/min/1.73m^2). Receives: Drug: MK-6183
Group C: Moderate RI	Experimental	Participants with moderate RI (Stage 3: eGFR ≥30 to <60 mL/min/1.73m^2). Receives: Drug: MK-6183
Group D: Severe RI	Experimental	Participants with severe RI (Stage 4: eGFR <30 mL/min/1.73m^2) not receiving HD. Receives: Drug: MK-6183
Group E: ESRD-HD	Experimental	Participants with ESRD who are receiving HD for at least 3 months preceding the initial dose in this study (Stage 5). Receives: Drug: MK-6183

What is being measured

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

Area Under the Plasma Concentration-time Curve (AUC) From Dosing to Last Measurable Concentration (AUC0-last) of MK-6183
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.
Measured: 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
AUC From Dosing to ∞ (AUC0-∞) of MK-6183
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.
Measured: 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
Maximum Plasma Drug Concentration (Cmax) of MK-6183
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.
Measured: 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
Apparent Total Body Clearance of MK-6183 From Plasma (CL)
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.
Measured: 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
Volume of Distribution at Steady State (Vss) of MK-6183
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.
Measured: 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
Apparent Plasma Half-life (t½) of MK-6183
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.
Measured: 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
Cumulative Amount of MK-6183 Excreted in Urine or Dialysate (Ae)
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).
Measured: 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
Renal Clearance of MK-6183 (CLr)
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.
Measured: 0 to 24, 24 to 48, and 48 to 72 hours post-dose
Dialysate Clearance of MK-6183 (CLd)
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).
Measured: 0 to 1, 1 to 2, 2 to 3, and 3 to 4 hours after starting HD
Fraction of the Administered Dose of MK-6183 Excreted Unchanged in Urine or Dialysate (Fe)
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).
Measured: 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

Secondary outcomes (2)

Number of Participants Experiencing an Adverse Event (AE)
An AE is any untoward medical occurrence in a participant administered a pharmaceutical product that does not necessarily have to have a causal relationship with this treatment.
Measured: Up to 12 days
Number of Participants Discontinuing From the Study Due to an AE
An AE is any untoward medical occurrence in a participant administered a pharmaceutical product that does not necessarily have to have a causal relationship with this treatment.
Measured: Up to 12 days

Timeline

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

11 Dec 201420 Apr 2015

First posted19 Jan 2015 (estimated)
Study start11 Dec 2014
Primary completion13 Apr 2015
Study completion20 Apr 2015

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 Healthy VolunteersStudies of the same condition, open and under way.
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: 40 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02341599
Sponsor's protocol ID: 6183-001
Other IDs: 618-REN-14-02, MK-6183-001
Status last verified: Feb 2019
First submitted: 12 Dec 2014
Last updated: 18 Feb 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
Individual data sharing: Yes: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

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Study at a glance

From the registry record, last updated by the sponsor on 18 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 1, Non-randomized, Parallel-group, Open-label Study to Characterize the Pharmacokinetics of a Single Intravenous Dose of CB-238,618 in Subjects With Varying Degrees of Renal Impairment Compared to Healthy Subjects
ClinicalTrials.gov ID: NCT02341599
Acronym / sponsor ID: 6183-001
Conditions: Healthy Volunteers, Renal Impairment
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 40 participants (actual)
Lead sponsor: Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)Industry (pharma, biotech, devices)
Study start: 11 Dec 2014 (actual)
Primary completion: 13 Apr 2015 (actual)
Study completion: 20 Apr 2015 (actual)
First posted: 19 Jan 2015 (estimated)
Results: Posted 18 Feb 2019

Clinical summary

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

Study design

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

Arm	Type	Receives
Group A: Healthy	Experimental	Drug: MK-6183Healthy participants with normal renal function (Stage 1: eGFR ≥90 mL/min/1.73m^2).
Group B: Mild RI	Experimental	Drug: MK-6183Participants with mild RI (Stage 2: eGFR ≥60 to <90 mL/min/1.73m^2).
Group C: Moderate RI	Experimental	Drug: MK-6183Participants with moderate RI (Stage 3: eGFR ≥30 to <60 mL/min/1.73m^2).
Group D: Severe RI	Experimental	Drug: MK-6183Participants with severe RI (Stage 4: eGFR <30 mL/min/1.73m^2) not receiving HD.
Group E: ESRD-HD	Experimental	Drug: MK-6183Participants with ESRD who are receiving HD for at least 3 months preceding the initial dose in this study (Stage 5).

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (1 listed)

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

Key exclusion criteria (8 listed)

For healthy participants (Group A): history or presence of any clinically significant illness (e.g., cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, oncologic, musculoskeletal, or psychiatric) or any other condition, including clinically significant anemia, which in the opinion of the investigator would jeopardize the safety of the participant or the validity of the study results
For participants with RI (Groups B to E): as above, except that RI and other medical conditions commonly associated with renal impairment (eg, hypertension, diabetes, which should be stable for at least three months preceding the initial dose of study medication in this study) are allowed
Clinically significant abnormalities on physical examination, medical history, 12-lead electrocardiogram (ECG), vital signs, or laboratory values, as judged by the investigator or designee. Subjects with renal impairment should have clinical laboratory values consistent with their disease and approved by the investigator
Evidence of clinically significant hepatic impairment including alanine aminotransferase or aspartate aminotransferase >1.5 × upper limit of normal (ULN) or bilirubin >1 × ULN
Hemoglobin <8 g/dL, unless considered stable and not clinically significant in the opinion of the investigator in subjects with ESRD and on HD

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-6183Also: CB-238,618MK-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.	Drug	Group A: Healthy, Group B: Mild RI, Group C: Moderate RI, Group D: Severe RI, Group E: ESRD-HD

Primary outcome

Area Under the Plasma Concentration-time Curve (AUC) From Dosing to Last Measurable Concentration (AUC0-last) of MK-6183
Time frame: 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
Time frame: 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
Time frame: 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)
Time frame: 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
Time frame: 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
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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).

2 secondary outcomes

Number of Participants Experiencing an Adverse Event (AE)
Time frame: Up to 12 days
Number of Participants Discontinuing From the Study Due to an AE
Time frame: Up to 12 days

Results and safety

Results posted to the registry on 18 Feb 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
Group A: Healthy	8	8
Group B: Mild RI	8	8
Group C: Moderate RI	8	8
Group D: Severe RI	8	8
Group E: ESRD-HD	8	8

Primary outcome: Area Under the Plasma Concentration-time Curve (AUC) From Dosing to Last Measurable Concentration (AUC0-last) of MK-6183

Time frame: 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. Mean (Standard Deviation). Unit: ug*hr/mL

Measure	Group A: Healthy n = 8	Group B: Mild RI n = 8	Group C: Moderate RI n = 8	Group D: Severe RI n = 8	Group E: ESRD-HD Period 1 n = 7	Group E: ESRD-HD Period 2 n = 7
Value	87.6 (8.49)	114.8 (23.20)	97.5 (25.71)	228.0 (63.24)	77.4 (8.79)	270.6 (76.70)

Population analysed: All participants who received MK-6183 and had viable results are included. One participant from Group E: Period 1 and 1 participant from Group E: Period 2 were excluded due to implausible concentration values.

Primary outcome: AUC From Dosing to ∞ (AUC0-∞) of MK-6183

Time frame: 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. Mean (Standard Deviation). Unit: ug*hr/mL

Measure	Group A: Healthy n = 8	Group B: Mild RI n = 8	Group C: Moderate RI n = 8	Group D: Severe RI n = 8	Group E: ESRD-HD Period 1 n = 7	Group E: ESRD-HD Period 2 n = 7
Value	87.8 (8.43)	115.1 (23.44)	97.8 (25.70)	228.6 (63.44)	86.8 (7.63)	296.3 (78.66)

Group A: Healthy vs Group B: Mild RI: LS mean ratio: 1.29 (90% CI 1.06 to 1.58)
Group A: Healthy vs Group C: Moderate RI: LS mean ratio: 1.08 (90% CI 0.889 to 1.32)
Group A: Healthy vs Group D: Severe RI: LS mean ratio: 2.51 (90% CI 2.06 to 3.06)

Primary outcome: Maximum Plasma Drug Concentration (Cmax) of MK-6183

Time frame: 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. Mean (Standard Deviation). Unit: ug/mL

Measure	Group A: Healthy n = 8	Group B: Mild RI n = 8	Group C: Moderate RI n = 8	Group D: Severe RI n = 8	Group E: ESRD-HD Period 1 n = 7	Group E: ESRD-HD Period 2 n = 7
Value	45.3 (5.23)	47.2 (8.19)	24.2 (5.95)	30.8 (3.90)	12.9 (4.60)	15.6 (6.59)

Group A: Healthy vs Group B: Mild RI: LS mean ratio: 1.04 (90% CI 0.846 to 1.27)
Group A: Healthy vs Group C: Moderate RI: LS mean ratio: 0.524 (90% CI 0.428 to 0.641)
Group A: Healthy vs Group D: Severe RI: LS mean ratio: 0.678 (90% CI 0.554 to 0.831)

Primary outcome: Apparent Total Body Clearance of MK-6183 From Plasma (CL)

Time frame: 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. Mean (Standard Deviation). Unit: L/hour

Measure	Group A: Healthy n = 8	Group B: Mild RI n = 8	Group C: Moderate RI n = 8	Group D: Severe RI n = 8	Group E: ESRD-HD Period 1 n = 7	Group E: ESRD-HD Period 2 n = 7
Value	11.5 (1.23)	9.0 (1.65)	5.5 (1.64)	2.4 (0.96)	2.9 (0.26)	0.9 (0.30)

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: Up to 12 days. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Group A: Healthy	0 of 8 (0%)	4 of 8 (50%)	0 of 8
Group B: Mild RI	0 of 8 (0%)	2 of 8 (25%)	0 of 8
Group C: Moderate RI	0 of 8 (0%)	2 of 8 (25%)	0 of 8
Group D: Severe RI	0 of 8 (0%)	3 of 8 (37.5%)	0 of 8
Group E: ESRD-HD	0 of 8 (0%)	4 of 8 (50%)	0 of 8

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 18 Feb 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: Yes. https://www.merck.com/clinical-trials/pdf/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

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing MK-6183 in people with Healthy Volunteers and Renal Impairment, run by Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA).

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 1 inclusion and 8 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 18 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.

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 18 Feb 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?

Area Under the Plasma Concentration-time Curve (AUC) From Dosing to Last Measurable Concentration (AUC0-last) of MK-6183 (time frame: 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). The study lists 10 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 NCT02341599.

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 18 Feb 2019.