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

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.

Study Overview

• Status: Completed
• Conditions: Infectious Peritonitis
• Intervention / Treatment: Drug: Dalbavancin via Intravenous Administration; Drug: Dalbavancin via Intraperitoneal Administration

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.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 89 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: NON_RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Dalbavancin via IV; 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; 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.
Active Comparator: Dalbavancin via IP; 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; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Colorado, Denver
• Investigators: Principal Investigator: Ty H Kiser, PharmD, University of Colorado, Denver

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2017
• Primary Completion (Actual): June 18, 2018
• Study Completion (Actual): June 18, 2018

Study Registration Dates

• First Submitted: October 13, 2016
• First Submitted That Met QC Criteria: October 20, 2016
• First Posted (Estimate): October 21, 2016

Study Record Updates

• Last Update Posted (Actual): March 19, 2021
• Last Update Submitted That Met QC Criteria: February 24, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Infections; Peritoneal Diseases; Intraabdominal Infections; Peritonitis; Anti-Infective Agents; Anti-Bacterial Agents; Dalbavancin; Teicoplanin
• Other Study ID Numbers: 16-1355

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No