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

NCT03869983 | Completed

• 2 other identifiers: CE-Iohexol Protocol -101Study Number-1802282
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Contrast-induced Nephropathy; Coronary Angiography

Keywords

Iohexol; Captisol®; cyclodextrin; radiographic; iodinated contrast medium; Omnipaque™

Outcome Measures

Primary Outcomes (2)

• Iohexol Area Under the Concentration-Time Curve (AUC) [ Time Frame: At designated time points up to 48 hours per Period ]

  Blood samples are to be collected at designated time points for the determination of the iohexol AUC. (Time points for CE-Iohexol Injection: Pre-dose, 30 seconds, 5, 10, 15, 20, 30 and 45 minutes, and 1, 2, 3, 4, 6, 8, 12, 24 and 48 hrs post dose. Time points for Omnipaque™ (iohexol) Injection: Pre-dose, 30 seconds, 5, 10, 15, 20, 30 and 45 minutes, and 1, 2, 3, 4, 6, 8, 12, 24 and 48 hrs post dose).

  48 hours

• Iohexol Maximum Plasma Concentration (Cmax) [ Time Frame: At designated time points up to 48 hours per Period ]

  Blood samples are to be collected at designated time points for the determination of the iohexol Cmax. (Time points for CE-Iohexol Injection: Pre-dose, 30 seconds, 5, 10, 15, 20, 30 and 45 minutes, and 1, 2, 3, 4, 6, 8, 12, 24 and 48 hrs post dose. Time points for Omnipaque™ (iohexol) Injection: Pre-dose, 30 seconds, 5, 10, 15, 20, 30 and 45 minutes, and 1, 2, 3, 4, 6, 8, 12, 24 and 48 hrs post dose).

  48 hours

Secondary Outcomes (1)

• Severity of all Adverse Events graded according to the Common Terminology Criteria for Adverse Events (CTCAE) [Time Frame: Day -1, 24h and 48h post dose].

  30 days

Study Arms (2)

Active Comparator

ACTIVE COMPARATOR

Omnipaque™ (iohexol) Injection, 755 mg/mL iohexol (350 mgI/mL)

Other: Omnipaque™ (iohexol) Injection

Experimental

EXPERIMENTAL

CE-Iohexol Injection, 755 mg/mL iohexol (350 mgI/mL)/50 mg CAPTISOL®/mL

Other: CE-Iohexol

Interventions

Omnipaque™ (iohexol) Injection OTHER

755 mg/mL iohexol (350 mgI/mL), 80 mL infused intravenously over approximately 20 seconds

Active Comparator

CE-Iohexol OTHER

755 mg/mL iohexol (350 mgI/mL)/50 mg CAPTISOL®/mL, 80 mL infused intravenously over approximately 20 seconds

Experimental

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• CyDex Pharmaceuticals, Inc.: lead
• Ligand Pharmaceuticals: collaborator
• Syneos Health: collaborator

Study Sites (1)

Syneos Health Clinique

Québec, Quebec, G1P0A2, Canada

Location

MeSH Terms

Interventions

Iohexol; Injections

Intervention Hierarchy (Ancestors)

Triiodobenzoic Acids; Iodobenzoates; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Keith Marschke, PhD

  Ligand Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: This is a double-blind study with limited access to the randomization code.
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Single center, randomized, double-blind, 2-period, crossover study

Study Record Dates

• First Submitted: March 7, 2019
• First Posted: March 11, 2019
• Study Start: April 12, 2019
• Primary Completion: May 15, 2019
• Study Completion: June 15, 2019
• Last Updated: August 16, 2019

Record last verified: 2019-03

Locations

CA (1)