Evaluation of Intravenous and Intraperitoneal Pharmacokinetics of Dalbavancin in Peritoneal Dialysis Patients
Condition: Infectious Peritonitis
MeSH terms: Peritonitis
Study type: Interventional
Phase: Phase 4

Summary: 
      This study will evaluate the pharmacokinetic properties of dalbavancin when administered as
      an intravenous infusion and instilled into the peritoneal space in patients who are
      undergoing peritoneal dialysis. The patients will receive intravenous dalbavancin followed by
      intensive plasma and peritoneal dialyses fluid sampling. Following a washout phase, the
      patients will then receive dalbavancin instilled into their peritoneal space followed by the
      same intensive plasma and peritoneal dialyses fluid sampling.
    

Detailed description: 
      This study is an open label, cross-over study, evaluating the plasma and peritoneal fluid
      pharmacokinetics (PK) of dalbavancin after either intravenous or intraperitoneal
      administration. In the first part of the study, ten patients will be administered dalbavancin
      on study day 0. Pharmacokinetic analysis will be conducted on days 0, 7, and 14. In the
      second part of the study, the same 10 patients will cross-over and then be administered
      dalbavancin on study day 0. Pharmacokinetic analysis will be conducted on days 0, 7, and 14.

      Sample Size:

      Ten (n=10) patients will be evaluated in this pharmacokinetic evaluation. Since this is a
      descriptive pharmacokinetic study a sample size calculation was not performed

      Plasma and peritoneal fluid sampling:

      Dalbavancin will be administered on study day 0. On the intravenous administration day
      dalbavancin will be administered as a 30-minute intravenous (IV) infusion. On the
      intraperitoneal administration day, dalbavancin will be administered in the peritoneal
      dialysis fluid with a 6 hour dwell time. On day 0, patients will undergo plasma and
      peritoneal fluid pharmacokinetic sampling for determination of dalbavancin concentrations at
      time zero, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, at time of volume exchange. Patients
      will be given a specimen collection cup and asked to collect ~30 ml of peritoneal dialysate
      following scheduled nocturnal dwell approximately 24 hours following the administration of
      dalbavancin administration. Patients will report for a single PK measurement on study days 7
      and 14. (18 total plasma and 18 total peritoneal fluid samples per patient). Blood samples
      will be drawn from a peripherally inserted intravenous catheter. Peritoneal fluid samples
      will be drawn from the already placed peritoneal dialysis catheter. Blood samples will be
      immediately centrifuged at 3000g and plasma and peritoneal fluid samples will be stored at
      -80°C until analysis.

      Description, Risks and Justification of Procedures and Data Collection Tools:

      Visit 1 and 4: (~8 hours): On visits 1 and 4 the patients will undergo intensive PK sampling.
      Subjects will be admitted to the Clinical and Translational Research Center (CTRC) in the
      morning and a "saline-lock" will be placed. A pre-dose sample and safety labs (comprehensive
      metabolic panel and urine pregnancy test for women of childbearing potential) will be
      obtained. The dalbavancin 1500 mg will either be administered intravenously (Visit 1) or into
      the intraperitoneal space (Visit 4) using the patient's existing peritoneal dialysis catheter
      with the patients currently prescribed dialysate. Following the blood and peritoneal fluid
      collection at the second dialysis volume exchange, the subjects will be discharged and asked
      to return at a scheduled time on day 7. Patients will also be given a specimen collection up
      with instructions to collect approximately 30 ml of peritoneal dialysate following their
      evening nocturnal dwell. The collected dialysate will be returned to the investigators.

      Visit 2, 3, 5, and 6: (~60 minutes): A "saline-lock" will be placed and blood and peritoneal
      fluid sample will be collected at each of these visits. All blood and peritoneal fluid draws
      will be completed at the CTRC. The patient will be discharged and follow up visits will be
      scheduled for day 14 or next intensive PK sampling visit.

      Washout: During the washout portion of this study the patients will not be asked to come in
      for any visits. This time-frame is to ensure that all of the medication (dalbavancin) has
      left the patients' system before administering another dose of the medication.

      Laboratory tests: The laboratory tests to be performed as part of this study include
      pregnancy testing to confirm eligibility and comprehensive metabolic panels to determine
      eligibility and evaluate safety.

      Pharmacokinetic Assessments: 4 mL of blood will be collected in a purple top
      (Ethylenediaminetetraacetic acid) tube and 4 mL of peritoneal fluid in a urine collection cup
      at pre-dose, and 1, 2, 3, 4, 6, dialysis volume exchange 1, 8, dialysis volume exchange 2
      post dose for quantification of dalbavancin. Blood and peritoneal fluid will be placed in an
      ice bath to chill until centrifuged. Plasma will be harvested within 30 minutes of each blood
      sample and will be stored at -80ºC until assaying.
    

Intervention name(s): Dalbavancin via Intravenous Administration; Dalbavancin via Intraperitoneal Administration
Intervention type(s): Drug; Drug
Intervention description(s): Patients will undergo plasma fluid pharmacokinetic sampling for determination of dalbavancin concentrations at time zero, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, at time of volume exchange.; Patients will undergo peritoneal fluid pharmacokinetic sampling for determination of dalbavancin concentrations at time zero, 1 hour, 2 hours, 3 hours, 4 hours, 6 hours, at time of volume exchange.
Intervention MeSH terms: Dalbavancin; Teicoplanin
Allocation: Non-Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Basic Science