Safety Study to Evaluate Daptomycin in Non-infected Adults Who Are Either on Hemodialysis or Continuous Ambulatory Peritoneal Dialysis (MK-3009-021)

Study Overview
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Brief Summary
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This study is to examine the safety of daptomycin in patients with End Stage Renal Disease.

Detailed Description
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This is an open label, non-randomized, non-comparative Phase 1 study designed to evaluate the PK profile, safety and tolerability of intravenous ( i.v.) daptomycin. Non-infected subjects with end stage renal disease undergoing hemodialysis (HD) or continuous ambulatory peritoneal dialysis (CAPD) will be enrolled in this in-patient study.

Official Title
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An Evaluation of the Pharmacokinetic Profile and Safety and Tolerability of Multiple Doses of 6mg/kg Intravenous Daptomycin in Non-Infected Adult Subjects With End Stage Renal Disease on Hemodialysis or Continuous Ambulatory Peritoneal Dialysis

Conditions
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End-Stage Renal Disease

Intervention / Treatment
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* Drug: daptomycin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent prior to any study-related procedure not part of normal medical care; Considered to be in appropriate health for study entry by the Investigator (e.g., no acute, debilitating medical problems) and appropriate candidate for completing study treatment; Male or female >18 years of age; If female of childbearing potential; willing to practice reliable birth control measures during study treatment, not lactating/pregnant, has a documented negative pregnancy test result within 24 hours prior to study medication administration, and willing to practice effective means of birth control for >28 days after study completion; If taking concomitant medications, subject must be on a relatively stable dose for at least two weeks prior to study medication administration; Functioning dialysis access (e.g. graft or fistula) for subjects undergoing HD and functioning dialysis access (e.g. peritoneal catheter) for subjects undergoing CAPD; ESRD on stable HD regimen of thrice weekly sessions with high-flux membranes or stable CAPD regimen. Exclusion Criteria: If female, pregnant or lactating; Received an investigational drug (including experimental biologic agents) within 30 days of study entry; Evidence of active ongoing infection; Unable to discontinue use of HMG-CoA reductase inhibitor therapy for duration of study; Has received any dose(s) of daptomycin within 5 days prior to receiving the first dose of study drug; Known to be allergic or intolerant to daptomycin; Body Mass Index (BMI) < 18.5 or > 40 kg/m2 [BMI = weight (kg)/height (m2)]; WBC >12, 000 cells/mm3 or <2500 cells/ mm3; Baseline creatinine phosphokinase (CPK) values >3X ULN (upper limit of normal); Alanine aminotransferase (ALT) >5X ULN; Aspartate aminotransferase (AST) >5X ULN; Known HIV-infected subjects with CD4 count ≤200 cells/mm3; Hemoglobin < 9 gm/dL; Active illicit drug and/or alcohol abuse; Myocardial infarction within last 6 months; Hospitalized for non-vascular or peritoneal dialysis (PD) access issues within 30 days; Subjects with a history of muscular disease (e.g., polymyositis, muscular dystrophy); Subjects with a history of neurological disease (e.g., Guillain Barré, multiple sclerosis), except stroke >6 months prior to study entry; Intramuscular injection within 7 days of study drug administration; Has a moribund clinical condition (i.e., high likelihood of death during the next 3 days); Is considered unlikely to comply with study procedures or to return for scheduled post-treatment evaluations; Neutropenic subjects with absolute neutrophil count ≤500 cells/mm3 History of rhabdomyolysis.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hemodialysis (HD) Participants<br>Participants will receive daptomycin 6 mg/kg by intravenous infusion (i.v.) at 48-hours intervals (with dialysis) for a total of 3 doses. | Drug: daptomycin<br>* 6mg/kg, i.v. infusion over 30 minutes; every 48 hours for a total of 3 doses<br>* Other names: Cubicin;|
| Experimental: Continuous Ambulatory Peritoneal Dialysis (CAPD) Participants<br>Participants will receive daptomycin 6 mg/kg, i.v., at 48-hours intervals for a total of 3 doses. | Drug: daptomycin<br>* 6mg/kg, i.v. infusion over 30 minutes; every 48 hours for a total of 3 doses<br>* Other names: Cubicin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics |  | Study Day 1, 3, 5 and 7 or 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and Tolerability |  | Study Days 1 through 16 or 17 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ESRD, dialysis, hemodialysis, continuous ambulatory peritoneal dialysis