Safety Study of CZ10 in Healthy Volunteers

Plain-language summary

A randomized, double-blind, placebo-controlled, parallel group, dose escalation study in healthy subjects to evaluate the safety, tolerability, pharmacokinetics and initial effectiveness of a novel intravenous CT contrast material (CZ10). This first-in-human clinical phase 1 trial will test the safety of escalating doses of CZ10 that has shown high safety and efficacy as a intravenous contrast agent in preclinical trials. The subjects for this study will be healthy adult volunteers, including obese but otherwise healthy subjects up to 450 lbs or the maximum allowable weight of the CT scanner, whichever is lighter. Subjects will be recruited and randomly assigned to cohort and test article. A total of 24 subjects will be evaluated with 18 subjects randomized to receive active drug and 6 subjects randomized to receive placebo control in a double blind manner. A total of three cohorts of 8 subjects will be enrolled. The first cohort subjects will receive a low dose, then if less than 2 subjects show severe adverse events, the second cohort will receive the expected clinical dose, then if less than 2 subjects show severe adverse events, the last cohort will receive a high dose of the intravenous test article. For each cohort, six subjects will be randomized to receive CZ10 and two to placebo. To increase subject safety, two initial subjects from each cohort will be randomized one to receive CZ10 and the other to receive placebo. If there are no serious adverse events through 3 days post dosing, then the remainder of the cohort will be enrolled. Subjects will be screened and enrolled up to 30 days prior to the day of test article dosing. Inclusion criteria are adult subjects willing to consent for the trial. Exclusion criteria are persons: (a) who are pregnant (as determined by a urine pregnancy test at the time of consent); (b) who have significant cardiovascular, respiratory, hepatic, gastrointestinal, hematological, neurological, psychiatric or other disease that may interfere with the objectives of the study and/or pose safety concerns; (c) Have evidence of moderate to severe renal insufficiency or renal failure (defined as an estimated glomerular filtration rate \<60 ml/minute); (d) who have an allergy to iodinated CT or other medical intravenous contrast material; (e) who are more than 450 pounds which would result in inability to be scanned on CT; or (f) have poor venous access such that an 18g venous cannula cannot be placed into the antecubital or other large superficial arm vein. Exclusion criteria also include women who are breastfeeding and women of childbearing age who are not using double protection birth control. Safety assessments will include monitoring of adverse events, vital signs (blood pressure, pulse rate, respiratory rate and oral temperature), clinical laboratory findings, 12-lead ECGs, subject reporting of symptoms, and physical examination findings. A physical examination will be performed at screening and on Day 2 and Day 7. A resting 12-lead ECG will be performed at screening, pre-dose and on Day 1 at 4 hours, Day 2, and Day 7. Vitals signs will be assessed at screening, at admission to the clinical research unit the day of dosing, then at 2, 4, and 7 hours after dosing, and on Day 2 and Day 7. Clinical laboratory tests (chemistry and hematology) will be performed at screening, pre-dose, at 7 hours after start of oral dosing, and Day 2 and 7 after dosing. A phone call interview to assess for symptoms will occur on day 15. In particular subjects will be monitored for possible allergic reaction, contrast material extravasation, and possible renal injury. If any adverse events are seen, the subject will be return to the clinical research unit for further assessment and possible treatment. Tentatively, the doses of CZ10 are expected to be 400, 800, and 1200 mg / kg of CZ10 but final doses will depend on preclinical and manufacturing data. The dose of test article will likely be limited by volume of material that can be bolus injected (maximum feasible dose). The placebo will be given at the same dose volume as the CZ10 drug product. At the conclusion of the study, the necessary safety data will be available to decide on whether and how to proceed with clinical phase 2 studies on patients with suspected or known vascular disease.

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