Evaluation of Intravenous and Intraperitoneal Pharmacokinetics of Dalbavancin in Peritoneal Dialysis Patients

Study Overview
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Brief Summary
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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
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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.

Official Title
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Evaluation of Intravenous and Intraperitoneal Pharmacokinetics of Dalbavancin in Peritoneal Dialysis Patients

Conditions
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Infectious Peritonitis

Intervention / Treatment
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* Drug: Dalbavancin via Intravenous Administration
* Drug: Dalbavancin via Intraperitoneal Administration


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 to ≤89 years of age Actively receiving chronic peritoneal dialysis Ability and willingness to provide written informed consent Exclusion Criteria: Patients currently receiving antimicrobial therapy or have received antibiotic therapy within 14 days prior to study Patients with known hypersensitivity reactions to dalbavancin or other glycopeptides Prisoners Pregnant or breastfeeding women Decisionally challenged patients

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 89 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Dalbavancin via IV<br>Dalbavancin will be administered via intravenous administration. 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. | Drug: Dalbavancin via Intravenous Administration<br>* 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.<br>|
| Active Comparator: Dalbavancin via IP<br>Dalbavancin will be administered as an intraperitoneal administration. 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. | Drug: Dalbavancin via Intraperitoneal Administration<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine Dalbavancin Plasma Area Under the Curve in Peritoneal Dialysis Patients After Intravenous and Intraperitoneal Administration | 14 day plasma concentrations | 14 days | 
| Determine Dalbavancin Peritoneal Fluid Area Under the Curve in Peritoneal Dialysis Patients After Intravenous and Intraperitoneal Administration | 14 day peritoneal fluid concentrations | 14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug, Graded According to NCI CTCAE Version 3.0 | Adverse reactions | 14 days | 
| Determine Dalbavancin Plasma Clearance in Peritoneal Dialysis Patients After Intravenous and Intraperitoneal Administration | Dalbavancin plasma clearance | 14 days | 
| Determine Dalbavancin Peritoneal Fluid Clearance in Peritoneal Dialysis Patients After Intravenous and Intraperitoneal Administration | Dalbavancin peritoneal fluid clearance | 14 days |