Study of Pharmacokinetics of a Single IV Dose of CB-238,618 in Subjects With Varying Degrees of Renal Impairment Compared to Healthy Subjects

ID: NCT02341599
Status: Completed
Phase: Phase 1
Start Date: December 11, 2014
First Submitted: December 12, 2014
Last Updated: September 13, 2017
Results: N/A
Sponsors & Collaborators: Cubist Pharmaceuticals LLC
Location: United States
Conditions: Healthy Volunteers, Renal Impairment
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.

Study Description

Brief Summary

The purpose of this study is to characterize the effect of renal function on the plasma, urine, and dialysate pharmacokinetic profile of CB-238,618 in humans. The study will also assess the safety profile and tolerability of CB-238,618 in subjects with varying degrees of renal impairment and in healthy subjects.

Detailed Description

Condition or disease Intervention/treatment Phase

Healthy Volunteers

Renal Impairment

Drug: CB-238,618 Group A
Other Names
Drug: CB-238,618 Group B
Other Names
Drug: CB-238,618 Group C
Other Names
Drug: CB-238,618 Group D
Other Names
Drug: CB-238,618 Group E
Other Names
Phase 1

Tracking Information

First Submitted DateDecember 12, 2014
Last Update Posted DateSeptember 13, 2017
Actual Start DateDecember 11, 2014
Actual Completion DateApril 20, 2015
Actual Primary Completion DateApril 13, 2015
Results First Submitted DateN/A
Received Results Disposit DateN/A

Current Primary Outcome Measures

  • The plasma pharmacokinetic (PK) profile of a single dose of CB-238,618 [Time Frame: Pre-dose through Day 6]

    The plasma pharmacokinetic (PK) profile of a single dose of CB-238,618 will be determined. The plasma pharmacokinetic parameters to be evaluated include, but are not limited to, maximum plasma concentration (Cmax), time of maximum plasma concentration (tmax), area under the curve (AUC), clearance (Cl), terminal half- life (t½), volume of distribution (Vd). These parameters will be used to determine potential differences in exposure when study drug is administered in healthy versus renally impaired subjects. The urine and dialysate pharmacokinetic parameters to be evaluated include, but are not limited to, the cumulative amount eliminated (Ae), the fraction eliminated (fe), and clearance (Cl) in humans.

Original Primary Outcome Measures

Not Available

Current Secondary Outcome Measures

  • Number of subjects with adverse events (incidence, severity, and type), changes in clinical laboratory tests (including chemistry, hematology, and urinalysis), vital signs, physical examination, and any concomitant (non-study) medications [Time Frame: Participants will be followed from the time of study drug administration (study day 1) through the last study follow up (may occur from study day 9 to study day 13)]

    Safety and tolerability will be evaluated by examining the incidence, severity, and type of adverse events, changes in clinical laboratory tests (including chemistry, hematology, and urinalysis), vital signs, physical examination, and any concomitant (non-study) medications.

Original Secondary Outcome Measures

Not Available

Study Design

Brief TitleStudy of Pharmacokinetics of a Single IV Dose of CB-238,618 in Subjects With Varying Degrees of Renal Impairment Compared to Healthy Subjects
Official TitleA 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
Brief Summary

The purpose of this study is to characterize the effect of renal function on the plasma, urine, and dialysate pharmacokinetic profile of CB-238,618 in humans. The study will also assess the safety profile and tolerability of CB-238,618 in subjects with varying degrees of renal impairment and in healthy subjects.

Detailed Description

Study TypeInterventional
Study PhasePhase 1
Estimated Enrollment
40
Allocation
Non-Randomized
Interventional Model
Parallel Assignment
Masking
None
Primary Purpose
Not Available
Conditions
Healthy Volunteers
Renal Impairment
Target Follow-Up Duration N/A
Biospecimen:
N/A
Sampling MethodN/A
Study PopulationN/A
Intervention
Drug: CB-238,618 Group A

Subjects in Group A will participate in one treatment period and will receive a single IV dose of 1000 mg CB-238,618.

Other Names
Drug: CB-238,618 Group B

Subjects in Group B will participate in one treatment period and will receive a single IV dose of 1000 mg CB-238,618.

Other Names
Drug: CB-238,618 Group C

Subjects in Group C will participate in one treatment period and will receive a single IV dose of 500 mg CB-238,618.

Other Names
Drug: CB-238,618 Group D

Subjects in Group D will participate in one treatment period and will receive a single IV dose of 500 mg CB-238,618.

Other Names
Drug: CB-238,618 Group E

Subjects in Group E will participate in two treatment periods, Treatment Period 1 and Treatment Period 2. These patients will receive a single IV dose of 250 mg CB-238,618 per treatment period, once before the hemodialysis (HD) session and once following the HD session.

Other Names
Study Groups/Cohorts
Group A
Healthy subjects with normal renal function (Stage 1, eGFR ≥90 mL/min/1.73m2 )

Group B
Subjects with mild renal impairment (Stage 2, eGFR ≥60- <90 mL/min/1.73m2)

Group C
Subjects with moderate renal impairment (Stage 3, eGFR ≥30- <60 mL/min/1.73m2)

Group D
Subjects with severe renal impairment (Stage 4, eGFR <30 mL/min/1.73m2) not receiving dialysis

Group E
Subjects with ESRD receiving HD for at least three months preceding the initial dose in this study (Stage 5)

Study Arms
Experimental Group A
Healthy subjects with normal renal function (Stage 1, eGFR ≥90 mL/min/1.73m2 )
Drug : CB-238,618 Group A
Subjects in Group A will participate in one treatment period and will receive a single IV dose of 1000 mg CB-238,618.

Experimental Group B
Subjects with mild renal impairment (Stage 2, eGFR ≥60- <90 mL/min/1.73m2)
Drug : CB-238,618 Group B
Subjects in Group B will participate in one treatment period and will receive a single IV dose of 1000 mg CB-238,618.

Experimental Group C
Subjects with moderate renal impairment (Stage 3, eGFR ≥30- <60 mL/min/1.73m2)
Drug : CB-238,618 Group C
Subjects in Group C will participate in one treatment period and will receive a single IV dose of 500 mg CB-238,618.

Experimental Group D
Subjects with severe renal impairment (Stage 4, eGFR <30 mL/min/1.73m2) not receiving dialysis
Drug : CB-238,618 Group D
Subjects in Group D will participate in one treatment period and will receive a single IV dose of 500 mg CB-238,618.

Experimental Group E
Subjects with ESRD receiving HD for at least three months preceding the initial dose in this study (Stage 5)
Drug : CB-238,618 Group E
Subjects in Group E will participate in two treatment periods, Treatment Period 1 and Treatment Period 2. These patients will receive a single IV dose of 250 mg CB-238,618 per treatment period, once before the hemodialysis (HD) session and once following the HD session.

Arm Intervention/Treatment
Experimental Group A
Healthy subjects with normal renal function (Stage 1, eGFR ≥90 mL/min/1.73m2 )
Drug : CB-238,618 Group A
Experimental Group B
Subjects with mild renal impairment (Stage 2, eGFR ≥60- <90 mL/min/1.73m2)
Drug : CB-238,618 Group B
Experimental Group C
Subjects with moderate renal impairment (Stage 3, eGFR ≥30- <60 mL/min/1.73m2)
Drug : CB-238,618 Group C
Experimental Group D
Subjects with severe renal impairment (Stage 4, eGFR <30 mL/min/1.73m2) not receiving dialysis
Drug : CB-238,618 Group D
Experimental Group E
Subjects with ESRD receiving HD for at least three months preceding the initial dose in this study (Stage 5)
Drug : CB-238,618 Group E

Recruitment Information

Recruitment Status:Completed
Enrollment40
Completion DateApril 20, 2015
Eligibility Criteria: Inclusion Criteria:
- Subjects with renal impairment are to have mild, moderate, or severe renal impairment, or ESRD requiring HD. ESRD subjects requiring HD should have been receiving HD on a three times/week schedule for at least three months preceding the initial dose in this study

Exclusion Criteria:
- For healthy subjects (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 subject or the validity of the study results
- For renally impaired subjects (Groups B to E): as above, except that renal insufficiency 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;
- Subjects 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
- Subjects with fluctuating or rapidly deteriorating renal function. Assessment of the stability of the subject's renal function will be determined by the investigator
- Subject has a currently functioning renal transplant and/or has been on significant immunosuppressant therapy, as determined by the investigator, within the last six months
GenderAll
Age18 Years to N/A
Accepts Healthy VolunteersAccepts Healthy Volunteers
Contacts
Not Available
Listed Location Countries
United States

Administrative Information

NCT Number:NCT02341599
Other Study ID Numbers
6183-001
618-REN-14-02
Has Data Monitoring CommitteeNo
U.S. FDA-regulated Product Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Device Product Not Approved or Cleared by U.S. FDA: No
IPD Sharing Statement
Not Available
Responsible Party,
Study Sponsor
Cubist Pharmaceuticals LLC
Collaborators
Not Available
Investigators
Principal Investigator
Christopher Galloway, MD
Davita Clinical Research
Principal Investigator
Jolene K Berg, MD
Davita Clinical Research