A Study for Ureter Visualization, Using ASP5354 in Subjects Undergoing Laparoscopic/Minimally Invasive Colorectal Surgery
Study Details
Study Description
Brief Summary
The primary purpose of this study is to determine the optimal dose of ASP5354 for ureter visualization in subjects undergoing laparoscopic/minimally invasive colorectal surgery This study will also investigate the safety, tolerability and the pharmacokinetics of ASP5354 in subjects undergoing laparoscopic/minimally invasive colorectal surgery.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Detailed Description
Participants will be randomly assigned at each dose level (dose A, B, C). During a standard minimally invasive surgery, visualization of the surgical field will be assessed following the placement of the near infrared fluorescence (NIR F) imaging system proximal to the ureter of interest and then ASP5354 will be administered.
Based on Visualization Review Committee (VRC) review of the initial 3 dose levels, if none of the doses selected have visualization, then additional two dose levels (dose D and E) will be added; if 1 dose selected has visualization, then the dose level D will be added. The dose level F will only be added if only the dose E level has visualization.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: ASP5354 dose-A group Participants will receive a single dose-A of ASP5354 once the surgical area of interest is in view. |
Drug: ASP5354
Intravenous
|
| Experimental: ASP5354 dose-B group Participants will receive a single dose-B of ASP5354 once the surgical area of interest is in view. |
Drug: ASP5354
Intravenous
|
| Experimental: ASP5354 dose-C group Participants will receive a single dose-C of ASP5354 once the surgical area of interest is in view. |
Drug: ASP5354
Intravenous
|
| Experimental: ASP5354 dose-D group Participants will receive a single dose-D of ASP5354 once the surgical area of interest is in view. This arm will be added only if the visualization in lower doses are not succeeded. |
Drug: ASP5354
Intravenous
|
| Experimental: ASP5354 dose-E group Participants will receive a single dose-E of ASP5354 once the surgical area of interest is in view. This arm will be added only if the visualization in lower doses are not succeeded. |
Drug: ASP5354
Intravenous
|
| Experimental: ASP5354 dose-F group Participants will receive a single dose-F of ASP5354 once the surgical area of interest is in view. This arm will be added only if the visualization in lower doses are not succeeded. |
Drug: ASP5354
Intravenous
|
Outcome Measures
Primary Outcome Measures
- Success rate of anatomical visualization of the index ureter(s) [Up to end of surgery (Day 1)]
The incidence of anatomical visualization of ureter(s) will be assessed by the investigator intraoperatively using a binary "Yes or No" question on the ability to visualize the ureter: "Can the ureter be adequately visualized with near-infrared fluorescence (NIR-F)"? If the answer to the question 30 minutes after ASP5354 administration and at the end of surgery = Yes, then anatomical visualization of the index ureter(s) of a participant is considered as a success.
Secondary Outcome Measures
- Number of participants with vital sign abnormalities and/or Adverse Events (AEs) [Up to Day 7]
Number of participants with potentially clinically significant vital sign values.
- Number of participants with electrocardiogram (ECG) abnormalities and/or AEs [Up to Day 7]
Number of participants with potentially clinically significant 12-ECG values.
- Number of participants with laboratory value abnormalities and/or AEs [Up to Day 7]
Number of participants with potentially clinically significant laboratory values.
- Number of participants with Treatment Emergent Adverse Events (TEAEs) and serious adverse events [Up to Day 7]
A TEAE is defined as an AE observed after administration of the IP and up to the follow up period. An investigational product (IP)-related TEAE is defined as any TEAE with a causal relationship assessed as "yes" by the investigator. Adverse event (AE) is considered "serious" if, in the view of either the investigator or sponsor, 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 hospitalization or prolongation to hospitalization, or other medically important event.
- Pharmacokinetics (PK) of ASP5354 in plasma: concentration [Up to end of surgery or 180 minutes after ASP5354 administration, whichever is later (Day 1)]
Concentration will be recorded from the PK plasma samples collected.
- PK of ASP5354 in urine: concentration [Up to end of surgery (Day 1)]
Concentration will be recorded from the PK urine samples collected.
- PK of ASP5354: amount of ASP5354 excreted in urine (Ae) [Up to end of surgery (Day 1)]
Ae will be recorded from the PK urine samples collected.
- PK of ASP5354: Percentage of ASP5354 dose excreted into urine (Ae%) [Up to end of surgery (Day 1)]
Ae(%) will be recorded from the PK urine samples collected.
Eligibility Criteria
Criteria
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.
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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 m2 and < 60. Subjects with an eGFR ≥ 60 mL/min/1.73 m2 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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Center for Colon and Rectal Surgery; AdventHealth Medical Group | Orlando | Florida | United States | 32804 |
| 2 | Ochsner Medical Center | New Orleans | Louisiana | United States | 70121 |
Sponsors and Collaborators
- Astellas Pharma Inc
Investigators
- Study Director: Medical Monitor, Astellas Pharma Inc
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 5354-CL-0201