Assessments
ureter anomalies, Cancer
URETER, EVENTS, ADVERSE EVENT, CANCER
Efficacy endpoints were based on intraoperative ureter fluorescence visualization of the surgical field elicited using an NIR-F imaging system (FDA 510[k] cleared Stryker 1688 AIM system) positioned to visualize the index ureter. After pudexacianinium was administered, surgery was initiated and ureter visualization was assessed at time points of 10, 20, 30, 45, and 60 min, then every 30 min thereafter, and/or until the last time point before removal of visualization instruments at the end of surgery. At the investigator’s discretion, the contralateral ureter could be visualized at similar time points when feasible. Video images were captured in bright-field (white light), NIR-F, and overlay modes and recorded during the entire surgery. Anatomical visualization of the index ureter was assessed intraoperatively by the investigator as “yes” or “no” on the ability to visualize the ureter at each time point. Qualitative assessment of fluorescence intensity was performed using a Likert scale (0=none, 1=mild, 2=moderate, and 3=strong).Adverse events were recorded and graded using the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0. Causal relationships between AEs and pudexacianinium were determined as assessed by the investigator. Safety assessments also included clinical laboratory evaluations (hematology, serum chemistry, and urinalysis), 12-lead electrocardiogram, vital signs measurements, and physical examination. Change from baseline in QTcF was determined for each participant using the mean value of triplicate readings at each time point.For the first three participants, blood samples for PK assessments were collected prior to pudexacianinium administration, at 10, 30, and 60 min after administration, then every 30 min thereafter until a final collection was obtained at the end of surgery (or at 180 min if the surgery was completed in less than 105 min). For the subsequent nine patients enrolled after the protocol was amended, blood was collected prior to administration, then at 10 min and either 30 or 60 min after administration, and at the end of surgery (or at 180 min if the duration of surgery was less than 105 min). Total urine samples to assess the amount of pudexacianinium excreted in the urine were collected during surgery. Before protocol amendment, point urine samples for PK assessments were collected prior to pudexacianinium administration, at 10, 30, and 60 min after administration, then every 30 min thereafter until a final collection was obtained at the end of surgery. Urine sample collection at all time points was not feasible during certain portions of surgical procedures. After protocol amendment, point urine samples were collected pre-dose and at the end of surgery.Fluorescence intensity was qualitatively assessed as dye visibility by the investigator at each time point using the 4-point Likert scale. The duration of visualization of the index ureter(s) was based on the result of the first and the last positive visualized time point. Investigators were asked to assess the clinical benefit of visualization provided by pudexacianinium during surgery by answering “yes” or “no” to the following questions:Was the location of the index ureter(s) as expected?Did visualization of the index ureter(s) occur with white light at 30 min after pudexacianinium administration?Did visualization of the index ureter(s) occur with white light at the end of surgery?Was NIR-F superior to white light in terms of visualization of the index ureter(s)?Did the location of the ureter visualized by NIR-F alter the operative plan?Were any ureter anomalies or abnormalities observed?The contralateral ureter was assessed using the same binary questions for anatomical visualization and Likert scale when feasible.A post hoc analysis (not protocol-specified) was conducted to quantitatively assess fluorescence intensity. Full color images of ureters taken during surgery were decomposed into red (R), green (G), and blue (B) components using ImageJ video analysis software (