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)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Renal Impairment
Lead sponsor: Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
Sponsor class: INDUSTRY
First posted: 2015-01-19
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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

Primary outcomes:
measure: Area Under the Plasma Concentration-time Curve (AUC) From Dosing to Last Measurable Concentration (AUC0-last) of MK-6183
timeFrame: 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
measure: AUC From Dosing to ∞ (AUC0-∞) of MK-6183
timeFrame: 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
measure: Maximum Plasma Drug Concentration (Cmax) of MK-6183
timeFrame: 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
measure: Apparent Total Body Clearance of MK-6183 From Plasma (CL)
timeFrame: 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
measure: Volume of Distribution at Steady State (Vss) of MK-6183
timeFrame: 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
measure: Apparent Plasma Half-life (t½) of MK-6183
timeFrame: 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
measure: Cumulative Amount of MK-6183 Excreted in Urine or Dialysate (Ae)
timeFrame: 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
measure: Renal Clearance of MK-6183 (CLr)
timeFrame: 0 to 24, 24 to 48, and 48 to 72 hours post-dose
measure: Dialysate Clearance of MK-6183 (CLd)
timeFrame: 0 to 1, 1 to 2, 2 to 3, and 3 to 4 hours after starting HD
measure: Fraction of the Administered Dose of MK-6183 Excreted Unchanged in Urine or Dialysate (Fe)
timeFrame: 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:
measure: Number of Participants Experiencing an Adverse Event (AE)
timeFrame: Up to 12 days
measure: Number of Participants Discontinuing From the Study Due to an AE
timeFrame: Up to 12 days
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: