Relative Bioavailability of CE-Iohexol (Captisol-enabled™ Iohexol) Injection and Omnipaque™ Injection

This is a single center, randomized, double-blind, 2-period, crossover study. A total of 24 subjects will be enrolled in the study; subjects will be dosed as 2 groups of 12 subjects each. Additional subjects may be enrolled into the study to obtain the statistical power of 90%. Subjects will attend a screening visit within 28 days prior to Period 1, and eligible subjects will then return to the clinic on the evening prior to Day -1. On Day 1, prior to dosing, subjects will be randomized to receive either CE-Iohexol Injection or the reference product during the first treatment period and the alternate product during the second treatment period. In each period, the study drug will be administered after a fasting period ≥8 hours. Each dose of intravenous iohexol will be separated by a minimum of a 7-day washout period. The test or reference product (iohexol 350 mg Iodine/mL, 80 mL) will be infused at a high flow rate of 4 mL/second for a dose of 400 mgI/kg for 70 kg subject. The test or reference product will be administered using a power injector. Plasma samples for determination of iohexol concentrations will be obtained from arm #2 (the arm not used for dosing) at 0 (pre-dose), 30 seconds, 5, 10, 15, 20, 30 and 45 minutes, and 1, 2, 3, 4, 6, 8, 12, 24, and 48 hours after infusion start; the 30-second sample obtained at the end of infusion. Subjects will be discharged from the clinic on Day 3 following collection of the 48-hour blood sample.

Inclusion criteria

• Women of childbearing potential who are sexually active with a non-sterile male partner must be using a medically acceptable form of birth control for the duration of the trial and for 30 days after the last dose of study drug
• BMI within the range of 18.5-35 kg/m2, inclusive, and body weight > 45 kg
• No significant disease or abnormal laboratory values
• Normal vital signs, without any clinically significant abnormalities
• Normal 12-lead electrocardiogram, without any clinically significant abnormalities of rate, rhythm or conduction
• Nonsmokers defined as not having smoked in the past 3 months prior to dosing
• Estimated glomerular filtration rate (eGFR) of > 60 mL/min/1.73 m2

Exclusion criteria

• Known hypersensitivity or allergy to iohexol, CAPTISOL®, Omnipaque™ or its excipients
• Known hypersensitivity or allergy to iodine or radio-opaque dyes
• Women who are pregnant or breast feeding
• History or presence of asthma or other pulmonary disease, thyroid disease (hypo- or hyperthyroidism), hepatitis or other liver disease
• Any disease or condition (medical or surgical) which, in the opinion of the investigator, might compromise a major system; or other conditions that may interfere with the absorption, distribution, metabolism or excretion of study drug, or would place the subject at increased risk
• Abnormal laboratory values which are considered clinically significant
• Positive screen for Hepatitis B (HbsAg, Hepatitis B Surface Antigen), Hepatitis C (anti HCV, Hepatitis C Antibody), or HIV (anti-HIV 1/2)
• Participation in a clinical research study involving the administration of an investigational or marketed drug or device within 30 days prior to the first dose
• Use of medication other than topical products without significant systemic absorption, hormonal contraceptives and hormone replacement therapy
• Unwilling to refrain from consumption of alcohol within 48 hours prior to each dose administration and during any in-patient period.
• Positive urine drug screen, positive alcohol breath test or positive cotinine test at screening and upon check-in to the study facility
• History of significant alcohol abuse within one year prior to screening or regular use of alcohol within six months prior to the screening visit
• Illicit drug use,significant mental illness, physical dependence to any opioid, or any history of drug abuse or addiction
• A history of difficulty with donating blood or with the insertion of large-calibre catheter
• Donation of plasma (500 mL) within 7 days prior to drug administration.
• Hemoglobin < 128 g/L (males) and < 115 g/L (females) and hematocrit < 0.36 L/L (males) and < 0.32 L/L (females) at screening
• Any history of photosensitivity