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)

Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)

Status and phase: Completed; Phase 1

Conditions: Renal Impairment; Healthy Volunteers

Treatments: Drug: MK-6183

Study type: Interventional

Funder types: Industry

Identifiers

NCT02341599

MK-6183-001 (Other Identifier)

618-REN-14-02 (Other Identifier)

6183-001

Details and patient eligibility

About

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).

Enrollment: 40 patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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40 participants in 5 patient groups

Group A: Healthy

Experimental group

Description:

Healthy participants with normal renal function (Stage 1: eGFR ≥90 mL/min/1.73m\^2).

Treatment:

Drug: MK-6183

Group B: Mild RI

Experimental group

Description:

Participants with mild RI (Stage 2: eGFR ≥60 to \<90 mL/min/1.73m\^2).

Treatment:

Drug: MK-6183

Group C: Moderate RI

Experimental group

Description:

Participants with moderate RI (Stage 3: eGFR ≥30 to \<60 mL/min/1.73m\^2).

Treatment:

Drug: MK-6183

Group D: Severe RI

Experimental group

Description:

Participants with severe RI (Stage 4: eGFR \<30 mL/min/1.73m\^2) not receiving HD.

Treatment:

Drug: MK-6183

Group E: ESRD-HD

Experimental group

Description:

Participants with ESRD who are receiving HD for at least 3 months preceding the initial dose in this study (Stage 5).

Treatment:

Drug: MK-6183