Pilot Study to Evaluate Safety, Tolerability, and Performance of the FAST PV Technology™ in Chronic Dialysis Patients

Study Overview
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Brief Summary
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The FAST Plasma Volume (PV) Technology will aid in determining the plasma and interstitial volumes of end stage renal disease patients before and after dialysis therapy, providing a more precise understanding of pre and post dialysis volumes and extent of volume removal during the course of treatment.

Detailed Description
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This is a pilot, single site, open-label study designed to evaluate the safety, tolerability, and performance of the FAST plasma volume (PV) Technology in dialysis patients. Administration of VFI will occur within 28 days of screening. Patients will receive 1 dose of VFI and 1 dose of iohexol approximately 4 hours prior to undergoing dialysis followed by a second dose of visible fluorescent injectate (VFI) and iohexol approximately 1 hour after completing dialysis. Patients will be discharged following completion of Day 1 activities. Patients will be seen and evaluated on their next 2 dialysis sessions for any adverse reaction by answering questions about their health, approximately on Day 3 and Day 8. A follow-up phone call will be performed on Day 31 (± 1 day).

Official Title
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A Pilot, Open-Label Study to Evaluate the Safety, Tolerability, and Performance of the FAST PV Technology™ in Chronic Dialysis Patients With Extremely Reduced or No Kidney Function

Conditions
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End Stage Renal Disease

Intervention / Treatment
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* Device: VFI using the FAST PV Technology


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects/patients must meet all inclusion criteria to be eligible for study participation. Males or females ≥ 18 years of age. Females must be of non-childbearing potential (eg, postmenopausal [defined cessation of regular menstrual periods for at least 1 year confirmed by age => 60 or surgically sterile by hysterectomy, bilateral oophorectomy, or bilateral tubal ligation [documentation required]) or be using a medically acceptable form of birth control (a barrier method, intrauterine device, or hormonal contraception) from screening through 30 days after administration of the last dose of VFI. Males who are sexually active and whose partners are females of childbearing potential must agree to practice abstinence or use condoms from screening through 90 days after administration of the last dose of VFI, and their partners must be willing to use a medically acceptable method of contraception (a barrier method, intrauterine device, or hormonal contraception) from screening through 90 days after administration of the last dose of VFI. Males must agree to not donate sperm from screening through 90 days after administration of the last dose of VFI. Subjects/patients must be able to communicate effectively with the study personnel. Patients must be on chronic hemodialysis for >= 3 months and oliguric defined as <= 2 urinary voids per day. Patients must have an average interdialytic weight gain of at least 2 kg. Patients must have an A-V dialysis shunt. Patients must have a functioning A-V dialysis shunt, either fistula or graft. Exclusion Criteria Subjects/patients will not be eligible for study participation if they meet any of the exclusion criteria, or will be discontinued at the discretion of the investigator if they develop any of the exclusion criteria during the study. Subject is a pregnant or nursing (lactating) woman, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test. History or presence of conditions which, in the judgment of the investigator, are known to interfere with the distribution, metabolism, or excretion of drugs History or presence of conditions that may place the subject/patient at increased risk as determined by the investigator. History of surgery or major trauma within 12 weeks of screening or surgery planned within 4 weeks of the study, including during study participation. Has taken other investigational drugs within 30 days or 5 half-lives of the investigational drug's PK, PD, or biological activity, whichever is longer, prior to first dose of VFI in this study. Prior exposure to VFI or known allergy or hypersensitivity to dextran, 5-aminofluorescein dye, or 2-sulfohexamine rhodamine dye. History of any clinically significant allergic or negative reactions, side effects, or anaphylaxis to iodine, dyes, shellfish, isotopes, or dextran molecules. Significant blood loss (> 450 mL) or has donated 1 or more units of blood or plasma within 4 weeks prior to study participation. Presence of significant hemodynamic instabilities defined as systolic BP <100 on dialysis requiring saline infusion in the past 4 weeks. Presence of ascites and/or 4+ anasarca. Any other condition or prior therapy that, in the investigator's opinion, would make the subject unsuitable for the study, or unable or unwilling to comply with the study procedures. Involved in the planning or conduct of this study. Unwilling or unlikely to comply with the requirements of the study. Clinically significant ongoing bleeding, changing hemoglobin, or experienced significant blood loss within the last 4 weeks. Had a PRBC transfusion in the prior 2 weeks Use of midodrine. Any other condition or prior therapy that, in the investigator's opinion, is likely to deteriorate during study participation Subjects suffering from significant non-cardiac diseases of other organ systems (e. g. Malignancies, significant neurological diseases). Subject has a psychiatric disease or a history of illicit drug use that would prohibit them from complying with study requirements. Use of hemodialysis catheter as primary vascular access for hemodialysis

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: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>Patients will receive one dose of visible fluorescent injectate (VFI)™ and one dose of iohexol approximately 4 hours prior to undergoing dialysis followed by a second dose of VFI and iohexol approximately 1 hour after completing dialysis. | Device: VFI using the FAST PV Technology<br>* The bolus IV administered visible fluorescent injectate (VFI) agent is comprised of a mixture of 2 different molecular weight carboxymethyl dextran molecules (5 kD and 150 kD) with different fluorescent dye molecules attached.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate Plasma Volume (PV) and Interstitial Volume (ISV) Using the FAST PV Technology and Iohexol in Patients on Chronic Dialysis Pre-dialysis | To measure quantitatively the ISV and PV of patients pre dialysis using the FAST PV Technology and iohexol measurement | 1 day | 
| Evaluate Plasma Volume (PV) and Interstitial Volume (ISV) Using the FAST PV Technology and Iohexol in Patients on Chronic Dialysis Post-dialysis | To measure quantitatively the ISV and PV of patients post dialysis using FAST PV Technology and the iohexol measurement | 1 day | 
| Evaluate the Difference in ISV and PV Pre- and Post Dialysis by the FAST PV Technology | Directly compare quantitative difference of ISV and PV measured by the FAST PV Technology to the volume removed during dialysis | 1 day | 
| Evaluate the Difference of ISV and PV Pre- and Post Dialysis by Iohexol | Directly compare quantitative difference of ISV and PV measured by the Iohexol measurement to the volume removed during dialysis | 1 day | 
| The Number of Patients Reporting Any Treatment-emergent Adverse Event. | To assess the safety and tolerability of visible fluorescent injectate (VFI)™ (employing the FAST PV Technology™) in chronic dialysis patients with extremely reduced or no renal function subjects will be monitored for adverse events and serious adverse events following administration of the first dose of the study drug through the end of the study. Treatment-emergent adverse events will be tabulated by system organ class, preferred term, and cohort. Treatment-emergent AEs will be further classified by severity and relationship to study product. | 59 days | 
| The Number of Patients Reporting Any Treatment-emergent Serious Adverse Event. | To assess the safety and tolerability of visible fluorescent injectate (VFI)™ (employing the FAST PV Technology™) in chronic dialysis patients with extremely reduced or no renal function subjects will be monitored for adverse events and serious adverse events following administration of the first dose of the study drug through the end of the study. Treatment-emergent adverse events will be tabulated by system organ class, preferred term, and cohort. Treatment-emergent AEs will be further classified by severity and relationship to study product. | 59 days | 
| The Number of Patients Reporting Any Drug-related Treatment-emergent Serious Adverse Event. | To assess the safety and tolerability of visible fluorescent injectate (VFI)™ (employing the FAST PV Technology™) in chronic dialysis patients with extremely reduced or no renal function subjects will be monitored for adverse events and serious adverse events following administration of the first dose of the study drug through the end of the study. Treatment-emergent adverse events will be tabulated by system organ class, preferred term, and cohort. Treatment-emergent AEs will be further classified by severity and relationship to study product. | 59 days | 
| The Number of Patients Reporting Any Drug Related Treatment-emergent Adverse Event. | To assess the safety and tolerability of visible fluorescent injectate (VFI)™ (employing the FAST PV Technology™) in chronic dialysis patients with extremely reduced or no renal function subjects will be monitored for adverse events and serious adverse events following administration of the first dose of the study drug through the end of the study. Treatment-emergent adverse events will be tabulated by system organ class, preferred term, and cohort. Treatment-emergent AEs will be further classified by severity and relationship to study product. | 59 days |