Clinical trial NCT00882557: Study to Evaluate Daptomycin Given During Dialysis and After Dialysis
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: End-stage Renal Disease
Renal Failure Chronic Requiring Hemodialysis
Keywords: End-stage renal disease
hemodialysis
chronic renal failure
Lead sponsor: Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
Sponsor class: INDUSTRY
First posted: 2009-04-16
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Evaluation of Area Under the Curve From Time 0 to Infinity
timeFrame: 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 outcomes:
measure: Treatment-emergent Adverse Events
timeFrame: 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).
Other outcomes:
measure: Maximum Plasma Concentration
timeFrame: 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)
measure: Time to Maximum Concentration
timeFrame: Up to 68 hours post dose
measure: Half-life
timeFrame: Up to 68 hours post dose
measure: Clearance of Daptomycin
timeFrame: Up to 68 hours post dose
measure: Volume of Distribution
timeFrame: Up to 68 hours post dose
Locations:
city: Cypress
country: United States
facility: West Coast Clinical Trials
state: California
city: Minneapolis
country: United States
facility: DaVita Clinical Research
state: Minnesota
Study officials:
affiliation: Cubist Pharmaceuticals LLC, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
name: Alistair Wheeler, MD, MFPM
role: STUDY_DIRECTOR
References: