- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02341599
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)
February 13, 2019 updated by: Cubist Pharmaceuticals LLC
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
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 impairment (RI), or participants with end-stage renal disease (ESRD) requiring hemodialysis (HD), based on estimated glomerular filtration rate (eGFR).
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
40
Phase
- Phase 1
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
Yes
Genders Eligible for Study
All
Description
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 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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Group A: Healthy
Healthy participants with normal renal function (Stage 1: eGFR ≥90 mL/min/1.73m^2).
|
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.
Other Names:
|
Experimental: Group B: Mild RI
Participants with mild RI (Stage 2: eGFR ≥60 to <90 mL/min/1.73m^2).
|
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.
Other Names:
|
Experimental: Group C: Moderate RI
Participants with moderate RI (Stage 3: eGFR ≥30 to <60 mL/min/1.73m^2).
|
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.
Other Names:
|
Experimental: Group D: Severe RI
Participants with severe RI (Stage 4: eGFR <30 mL/min/1.73m^2)
not receiving HD.
|
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.
Other Names:
|
Experimental: Group E: ESRD-HD
Participants with ESRD who are receiving HD for at least 3 months preceding the initial dose in this study (Stage 5).
|
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.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
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
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.
|
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
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.
|
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)
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.
|
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
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.
|
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
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.
|
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)
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).
|
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)
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.
|
0 to 24, 24 to 48, and 48 to 72 hours post-dose
|
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).
|
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)
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).
|
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 Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants Experiencing an Adverse Event (AE)
Time Frame: Up to 12 days
|
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.
|
Up to 12 days
|
Number of Participants Discontinuing From the Study Due to an AE
Time Frame: Up to 12 days
|
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.
|
Up to 12 days
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
December 11, 2014
Primary Completion (Actual)
April 13, 2015
Study Completion (Actual)
April 20, 2015
Study Registration Dates
First Submitted
December 12, 2014
First Submitted That Met QC Criteria
January 14, 2015
First Posted (Estimate)
January 19, 2015
Study Record Updates
Last Update Posted (Actual)
February 18, 2019
Last Update Submitted That Met QC Criteria
February 13, 2019
Last Verified
February 1, 2019
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 6183-001
- 618-REN-14-02 (Other Identifier: Cubist Study Number)
- MK-6183-001 (Other Identifier: Merck Protocol Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
YES
IPD Plan Description
https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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