A Study for Ureter Visualization, Using ASP5354 in Subjects Undergoing Laparoscopic/Minimally Invasive Colorectal Surgery

Study Overview
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Brief Summary
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The primary purpose of this study was to determine the optimal dose of ASP5354 for ureter visualization in participants undergoing laparoscopic/minimally invasive colorectal surgery This study also investigated the safety, tolerability and the pharmacokinetics of ASP5354 in participants undergoing laparoscopic/minimally invasive colorectal surgery.

Detailed Description
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Participants were randomly assigned at each dose level (dose A, B, C). During a standard minimally invasive surgery, visualization of the surgical field was assessed following the placement of the near infrared fluorescence (NIR F) imaging system proximal to the ureter of interest and then ASP5354 was administered. Based on Visualization Review Committee (VRC) review of the initial 3 dose levels, if none of the doses selected had visualization, then additional two dose levels (dose D and E) was planned to be added; if 1 dose selected has visualization, then the dose level D was planned to be added. The dose level F was planned to be added if only the dose E level has visualization.

Official Title
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A Phase 2 Randomized Open-label, Dose-ranging Study for Ureter Visualization Using ASP5354 in Subjects Undergoing Laparoscopic/Minimally Invasive Colorectal Surgery

Conditions
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Laparoscopic/Minimally Invasive Colorectal Surgery

Intervention / Treatment
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* Drug: Pudexacianinium chloride


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject is scheduled to undergo laparoscopic/minimally invasive colorectal surgery. Subject will need visualization of the ureter(s). Female subject is not pregnant and at least 1 of the following conditions apply: Not a woman of childbearing potential (WOCBP) WOCBP who agrees to follow the contraceptive guidance from the time of informed consent through at least 30 days after final study treatment administration. Female subject must agree not to breastfeed starting at screening and throughout the study period. Female subject must not donate ova starting at first dose of investigational product (IP) and throughout the study period and for 30 days after final study treatment administration. Male subject with female partner(s) of childbearing potential (including breastfeeding partner) must agree to use contraception throughout the treatment period and for 30 days after final study treatment administration. Male subject must not donate sperm during the treatment period and for 30 days after final study treatment administration. Male subject with pregnant partner(s) must agree to remain abstinent or use a condom for the duration of the pregnancy throughout the study period and for 30 days after final study treatment administration. Subject agrees not to participate in another interventional study while participating in the present study. Subjects enrolled after optimal dose determination: Subject has any of the following values at screening: Body mass index > 25 Estimated glomerular filtration rate (eGFR) ≥ 15 mL/min/1.73 m^2 and < 60. Subjects with an eGFR ≥ 60 mL/min/1.73 m^2 may be considered after discussion with the medical monitor. Exclusion Criteria: Subject is anticipated to require ureteral stenting during surgery. Subject has a history of known retroperitoneal fibrosis. Subject has an active urinary tract infection. Subject has received any investigational therapy within 28 days or 5 half-lives, whichever is longer, prior to screening. Subject has any condition that makes the subject unsuitable for study participation. Subject has a known or suspected hypersensitivity to ASP5354, indocyanine green (ICG) or any components of the formulation used. Subject has had previous exposure to ASP5354. Subject has moderate to severe cardiac disease that limits daily functioning (New York Heart Association Class III-IV) or other medical conditions that the investigator feels would impact safety or study compliance. Subject has a mean resting heart rate ≤ 45 bpm or ≥ 115 bpm, mean systolic blood pressure (SBP) ≥ 160 mmHg or mean diastolic blood pressure (DBP) ≥ 100 mmHg on day -1. If the mean blood pressure exceeds the limits above, repeat readings can be taken. Subject who has adequately controlled blood pressure is eligible. Subject has a mean corrected QT interval (Triplicate electrocardiogram [ECG]) using Fridericia's formula (QTcF) > 430 msec (for male subjects) and > 450 msec (for female subjects) on day -1. If the mean QTcF exceeds the limits above, the mean of 1 additional triplicate ECG may be taken. Subject has any of the following screening laboratory values: Hemoglobin ≤ 9 g/dL Absolute neutrophil count ≤ 1500/µL Platelet count ≤ 100000/µL eGFR < 60 mL/min/1.73 m^2 (Not applicable to subjects enrolled after optimal dose determination.) Serum bilirubin ≥ 2 × upper limit of normal (ULN) Aspartate aminotransferase (AST) or serum glutamic oxaloacetic transaminase ≥ 2.5 × ULN Alanine aminotransferase (ALT) or serum glutamic pyruvic transaminase ≥ 2.5 × ULN Subject has taken ICG or other near-infrared fluorescence (NIR)-F imaging agents within 48 hours prior to study treatment administration. Subject has taken diuretics or inhibitors of renal transporters defined by Food and Drug Administration (FDA) within 48 hours prior to study treatment administration. Subject has used any illicit drugs, unless legally prescribed and is not being abused (amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine and opiates) within 1 month prior to day -1. Subject has a history of alcohol abuse. Subject should not have consumed any alcohol within 48 hours of surgery.

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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pudexacianinium chloride - Dose Level A<br>Participants received single dose of pudexacianinium chloride at dose level A by intravenous (IV) bolus infusion on day 1 once the surgical area of interest is in view. | Drug: Pudexacianinium chloride<br>* Intravenous<br>* Other names: ASP5354;|
| Experimental: Pudexacianinium chloride - Dose Level B<br>Participants received single dose of pudexacianinium chloride at dose level B by IV bolus infusion on day 1 once the surgical area of interest is in view. | Drug: Pudexacianinium chloride<br>* Intravenous<br>* Other names: ASP5354;|
| Experimental: Pudexacianinium chloride - Dose Level C<br>Participants received single dose of pudexacianinium chloride at dose level C by IV bolus infusion on day 1 once the surgical area of interest is in view. | Drug: Pudexacianinium chloride<br>* Intravenous<br>* Other names: ASP5354;|
| Experimental: Pudexacianinium chloride - Dose Level B - Dose Expansion<br>Participants who were enrolled in the dose expansion group received single dose of pudexacianinium chloride at dose level B by IV bolus infusion on day 1 once the surgical area of interest is in view. | Drug: Pudexacianinium chloride<br>* Intravenous<br>* Other names: ASP5354;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Successful Anatomical Visualization of the Index Ureter(s) | The anatomical visualization of the index ureter(s) was assessed by the investigator intraoperatively using a binary Yes or No question on the ability to visualize the ureter and was assessed as successful, if both 30 minutes after pudexacianinium chloride dosing and at end of surgery the visualization was assessed as positive (Yes)/successful. For imputation of missing values at 30 minutes after pudexacianinium chloride administration, the nearest time points before and after the 30 minutes was considered. If both time points (before and after 30 minutes) were successful, 30 minutes anatomical visualization was imputed as successful. If both time points were not successful, then 30 minutes anatomical visualization was imputed as not successful, and all other cases were not imputed. | 30 minutes postdose through end of surgery (on day 1) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment Emergent Adverse Events | An adverse event (AE) was any untoward medical occurrence in a participant administered an investigational product (IP), and which did not necessarily have a causal relationship with the treatment. An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of IP whether or not considered related to the IP. A TEAE was defined as an AE observed after administration of the IP and up to the follow-up period. An AE was considered serious if the event: results in death;is life-threatening; results in persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions;results in congenital anomaly, or birth defect;requires inpatient hospitalization (except for planned procedures as allowed per study) or leads to prolongation of hospitalization; Other medically important events. | From first dose of study drug until follow-up period (day 10) | 
| Plasma Concentration of Pudexacianinium Chloride | Plasma concentration of pudexacianinium chloride was reported from the blood samples collected. Concentrations below the lower limit of quantification (1 nanogram per milliliter [ng/mL]) are set to zero. | Predose, 10, 30, 60, 90, 120 minutes, end of surgery, 180 mins post dose | 
| Urine Concentration of Pudexacianinium Chloride | Urine concentration of pudexacianinium chloride was reported from the urine samples collected. Concentrations below the lower limit of quantification (20 ng/mL) are set to zero. | Predose, 10, 30, 60, 90 minutes, end of surgery, 180 mins post dose | 
| Amount of Pudexacianinium Chloride Excreted in Urine (Ae) During Surgery | Amount of pudexacianinium chloride excreted in urine during surgery was reported. | During surgery (on day 1) | 
| Percentage of Pudexacianinium Chloride Dose Excreted Into Urine (Ae%) During Surgery | Percentage of pudexacianinium chloride dose excreted into urine during surgery was reported. | During surgery (on day 1) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ASP5354, ureter visualization, imaging agent, near infrared fluorescence