Study to Evaluate Daptomycin Given During Dialysis and After Dialysis

Study Overview
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Brief Summary
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The purpose of this study is to determine whether daptomycin at a higher dose given during the last 30 minutes of a dialysis session is equal to a lower dose of daptomycin given after a dialysis session.

Official Title
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A Prospective, Randomized, Crossover-design Study to Evaluate the Pharmacokinetics and Safety of Daptomycin Administered at 9 mg/kg During and 6 mg/kg After Hemodialysis

Conditions
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End-stage Renal Disease, Renal Failure Chronic Requiring Hemodialysis

Intervention / Treatment
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* Drug: daptomycin
* 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; Male or female ≥ 18 years of age; If female of childbearing potential; willing to practice reliable birth control measures during study treatment and for at least 28 days after study completion, not lactating or pregnant, and has a documented negative pregnancy test result within 24 hours prior to study medication administration; End-stage renal disease on stable (for at least 2 weeks) hemodialysis regimen, three times weekly using high-flux membranes; Functioning hemodialysis access (for example, graft or fistula); Considered to be in appropriate health for study entry by the Investigator (for example, no acute, debilitating medical problems) and appropriate candidate for completing study treatment; If taking concomitant medications, subject must be on a relatively stable dose for at least two weeks prior to study drug administration. Exclusion Criteria: Received an investigational drug (including experimental biologic agents) within 30 days of study drug administration; Has received any dose of daptomycin within 7 days prior to study drug administration; Known to be allergic or intolerant to daptomycin; Evidence of active ongoing infection; Known human immunodeficiency virus (HIV) infection with CD4 count ≤ 200 cells/mm3; Active illicit drug use or alcohol abuse; Myocardial infarction within last 6 months; Subject with a history of muscular disease (for example, polymyositis, muscular dystrophy); Subject with a history of neurological disease (for example, Guillain Barré, multiple sclerosis), except stroke > 6 months prior to study entry; Intramuscular injection within 7 days of study drug administration; Body mass index (BMI) ≤ 18.5 or ≥ 40 kg/m2 (BMI = weight [kg]/height [m2]); WBC ≥ 12, 000 cells/mm3 or ≤ 2500 cells/ mm3; Neutropenic subject with absolute neutrophil count ≤ 500 cells/mm3; Baseline CPK values ≥ 3X ULN (upper limit of normal); Alanine aminotransferase (ALT) > 5XULN; Aspartate aminotransferase (AST) > 5XULN; Hemoglobin ≤ 9 gm/dL; Is considered unlikely to comply with study procedures or to return for scheduled post-treatment evaluations; 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: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>9 mg/kg of daptomycin administered during the last 30 minutes of a hemodialysis session. | Drug: daptomycin<br>* intradialytic: 9 mg/kg during the last 30 minutes of dialysis<br>* Other names: Cubicin;|
| Experimental: B<br>Post dialysis dosing | Drug: daptomycin<br>* 6 mg/kg administered after a hemodialysis session<br>* Other names: Cubicin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of Area Under the Curve From Time 0 to Infinity | Area under the plasma concentration versus time curve from time 0 to infinity for daptomycin doses | Within 30 minutes prior to the start of the infusion, mid-infusion, and end of the infusion; at 1, 2, 4, 6, 9, 24, and 48 hours after the end of the infusion; and just prior to the next hemodialysis session (i.e., 68 hours post-infusion) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment-emergent Adverse Events | Safety was monitored throughout the study, including observation and reports of AEs as well as changes in physical findings, vital signs, ECGs, and laboratory tests. | Up to 9 days after the last dose of study drug administration (Day 13 to Day 17 for those dosed on Day 8 and Day 20 to Day 24 for those dosed on Day 15). | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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End-stage renal disease, hemodialysis, chronic renal failure