relative bioavailability of ce-iohexol (captisol-enabled™ iohexol) injection and omnipaque™ injection

Conditions: Contrast-induced Nephropathy; Coronary Angiography

Summary: this study is designed to compare the bioavailability of the test product(ce-iohexol injection) and the reference product iohexol injection (omnipaque™) following intravenous injection in normal healthy volunteers. the secondary objective is to assess the safety and tolerability of the treatments administered. captisol® is present to improve stability and to potentially reduce the risk of contrast-induced acute kidney injury(ci-aki) associated with iohexol administration.

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.

Eligibility criteria:
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

Keywords: iohexol captisol® cyclodextrin radiographic iodinated contrast medium omnipaque™