Phase 1
N=40
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)
Healthy Volunteers · Renal Impairment
Bottom Line
View on ClinicalTrials.gov: NCT02341599 ↗Enrolled (actual)
40
Serious AEs
0.0%
Results posted
Feb 2019
Primary outcome: Primary: Area Under the Plasma Concentration-time Curve (AUC) From Dosing to Last Measurable Concentration (AUC0-last) of MK-6183 — 87.6; 114.8; 97.5; 228.0 ug*hr/mL
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- MK-6183 (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
- Primary completion
- Apr 2015
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Area Under the Plasma Concentration-time Curve (AUC) From Dosing to Last Measurable Concentration (AUC0-last) of MK-6183 |
87.6; 114.8; 97.5; 228.0; 77.4; 270.6 | — |
| PRIMARY AUC From Dosing to ∞ (AUC0-∞) of MK-6183 |
87.8; 115.1; 97.8; 228.6; 86.8; 296.3 | — |
| PRIMARY Maximum Plasma Drug Concentration (Cmax) of MK-6183 |
45.3; 47.2; 24.2; 30.8; 12.9; 15.6 | — |
| PRIMARY Apparent Total Body Clearance of MK-6183 From Plasma (CL) |
11.5; 9.0; 5.5; 2.4; 2.9; 0.9 | — |
| PRIMARY Volume of Distribution at Steady State (Vss) of MK-6183 |
21.4; 22.8; 23.9; 19.4; 52.1; 25.3 | — |
| PRIMARY Apparent Plasma Half-life (t½) of MK-6183 |
2.1; 2.8; 4.0; 6.8; 18.1; 19.2 | — |
| PRIMARY Cumulative Amount of MK-6183 Excreted in Urine or Dialysate (Ae) |
840.5; 699.1; 360.0; 309.1; 122.9 | — |
| PRIMARY Renal Clearance of MK-6183 (CLr) |
9.6; 6.1; 4.0; 1.7 | — |
| PRIMARY Dialysate Clearance of MK-6183 (CLd) |
1.4 | — |
| PRIMARY Fraction of the Administered Dose of MK-6183 Excreted Unchanged in Urine or Dialysate (Fe) |
84.0; 69.9; 72.0; 61.8; 49.2 | — |
| SECONDARY Number of Participants Experiencing an Adverse Event (AE) |
4; 2; 2; 3; 4 | — |
| SECONDARY Number of Participants Discontinuing From the Study Due to an AE |
0; 0; 0; 0; 0 | — |
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 impairment (RI), or participants with end-stage renal disease (ESRD) requiring hemodialysis (HD), based on estimated glomerular filtration rate (eGFR).
Eligibility Criteria
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
Data sourced from ClinicalTrials.gov (NCT02341599). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.