Internal decision

Randomized parallel group study comparing the renal safety of Captisol-Enabled™ Iohexol (CE-Iohexol) Injection and Omnipaque™ (Iohexol) Injection in patients with impaired renal function undergoing coronary angiography.

The purpose of this trial is to demonstrate a reduction in the incidence of contrast-induced acute kidney injury (CI-AKI), also known as contrast-induced nephropathy (CIN), and the equivalence of image quality following administration of Captisol-Enabled™-Iohexol (CE-Iohexol) Injection compared to Omnipaque™(Iohexol) Injection in patients with impaired renal function undergoing invasive coronary angiography.

Inclusion Criteria:

1. Male or female aged ≥18 years

2. Referred for a coronary angiography (with or without percutaneous coronary intervention) and must meet either 1 of the following criteria:

   1. Estimated glomerular filtration rate (eGFR) <45 and ≥15 mL/min/1.73 m2 as determined by the Chronic Kidney Disease Epidemiology Collaboration (CKD- EPI) equation; or

   2. eGFR <60 and ≥45 mL/min/1.73 m2 as determined by the CKD-EPI equation and at least 1 of the following conditions:

      • Age >75 years
      • Diabetes mellitus with glycosylated hemoglobin (HbA1c) ≤10%
      • New York Heart Association (NYHA) class II or III heart failure
      • Albuminuria with urine albumin-to-creatinine ratio (UACR) or urine protein-to- creatinine ratio (UPCR) ≥300 and ≤4000 mg/g; or
      • Anemia, with hemoglobin levels ≥8 g/dL but <12.0 g/dL in women and <13.0 g/dL in men, as defined by the World Health Organization

3. If female, must also meet any 1 of the following criteria:

   1. Surgically sterile with bilateral tubal ligation, bilateral salpingectomy, bilateral oophorectomy, or hysterectomy
   2. Postmenopausal with amenorrhea for at least 1 year and follicle-stimulating hormone in the postmenopausal range; or
   3. Is a woman of childbearing potential, non-pregnant and non-lactating at Screening, and must agree to use a protocol-recommended method of birth control or abstain from heterosexual intercourse, beginning at least 30 days prior to and until 30 days following investigational contrast agent administration

4. If a male who can father a child, must also meet all of the following criteria:

   1. Willing to use a protocol-recommended method of birth control, ie, a double barrier approach (eg, condoms with spermicide) or abstain from heterosexual intercourse with women of childbearing potential, from Day 1 until at least 90 days after investigational contrast agent administration; and
   2. Willing to refrain from sperm donation from Day 1 until at least 90 days after investigational contrast agent administration

5. Willing to undergo protocol-recommended blood and urine collections, physical examinations, and laboratory investigations; and

6. Willing and able to provide written informed consent

Exclusion criteria

1. eGFR <15 mL/min/1.73 m2

2. Reduction in eGFR by approximately 25% that is considered to be acute per the Investigator's judgment

3. Body weight >125 kg

4. Uncorrected clinically significant abnormalities of clinical laboratory assessments which, in the Investigator's opinion, will interfere with the study conduct, including but not limited to the following:

   1. HbA1c >10%
   2. Blood glucose >270 mg/dL
   3. Hemoglobin <8 g/dL
   4. Albuminuria with UACR or UPCR >4000 mg/g; or
   5. Aspartate aminotransferase or alanine aminotransferase >3 x upper limit of reference range

5. Positive test for severe acute respiratory syndrome coronavirus 2 RNA at Screening;

6. Positive test for human immunodeficiency virus antibody, hepatitis B surface antigen, or hepatitis C virus RNA at Screening

7. Uncontrolled hypertension, with systolic blood pressure (BP) >180 mmHg or diastolic BP >110 mmHg at Screening, based on the average of 3 BP measurements obtained from the patient's dominant arm

8. Hypotension, that is considered to be of recent occurrence per the Investigator's judgment, and required resuscitation with intravenous fluids

9. Non-cardiac acute illness or injuries that, in the opinion of the Investigator, could put the patient at risk or obscure the interpretation of the results of the study

10. Known allergy or sensitivity to iodinated contrast agents, Captisol, or any of the excipients in the study contrast agent that cannot be adequately managed with prophylactic treatment per the Investigator's judgment and Good Clinical Practice

11. Known allergy to heparin, history of heparin-induced thrombocytopenia, or history of heparin induced thrombocytopenia with thrombosis

12. Chronic disease(s) that, in the opinion of the Investigator, could interfere with (or for which the treatment might interfere with) the conduct of the study or interpretation of the study results or would place the patient at undue risk by participating in the study, including but not limited to the following:

    1. NYHA class IV or decompensated heart failure; or
    2. Cirrhosis of the liver

13. Inability to receive periprocedural intravenous volume expansion

14. Received contrast media within 10 days prior to the scheduled coronary angiography

15. Unable or not willing to come off non-steroidal anti-inflammatory drugs, including ibuprofen, for at least 24 hours before the scheduled procedure

Subjects, and site personnel evaluating the subjects, will be blinded to the contrast media administered.