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

Primary Purpose

Contrast-induced Nephropathy, Coronary Angiography

Status

Completed

Phase

Not Applicable

Locations

Canada

Study Type

Interventional

Intervention

Omnipaque™ (iohexol) Injection

CE-Iohexol

About this trial

This is an interventional prevention trial for Contrast-induced Nephropathy focused on measuring Iohexol, Captisol®, cyclodextrin, radiographic, iodinated contrast medium, Omnipaque™

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

Syneos Health Clinique

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Active Comparator

Experimental

Arm Description

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

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

Outcomes

Primary Outcome Measures

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).

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).

Secondary Outcome Measures

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].

An adverse event is defined as any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. The severity of all adverse events will be graded according to the CTCAE version 4.0 from dosing until 30 days post-dose

Full Information

NCT ID

NCT03869983

First Posted

March 7, 2019

Last Updated

August 14, 2019

Sponsor

CyDex Pharmaceuticals, Inc.

Collaborators

Ligand Pharmaceuticals, Syneos Health

1. Study Identification

Unique Protocol Identification Number

NCT03869983

Brief Title

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

Official Title

A Randomized, Double-Blind, 2-Period Crossover Trial to Determine the Relative Bioavailability of CE-Iohexol (Iohexol/Sulfobutylether-β-Cyclodextrin ( Captisol®)) Injection and Omnipaque™ (Iohexol) Injection in Healthy Adult Volunteers

Study Type

Interventional

2. Study Status

Record Verification Date

March 2019

Overall Recruitment Status

Completed

Study Start Date

April 12, 2019 (Actual)

Primary Completion Date

May 15, 2019 (Actual)

Study Completion Date

June 15, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

CyDex Pharmaceuticals, Inc.

Collaborators

Ligand Pharmaceuticals, Syneos Health

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Yes

Data Monitoring Committee

5. Study Description

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.

Detailed Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Contrast-induced Nephropathy, Coronary Angiography

Keywords

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

7. Study Design

Primary Purpose

Prevention

Study Phase

Not Applicable

Interventional Study Model

Crossover Assignment

Model Description

Single center, randomized, double-blind, 2-period, crossover study

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Masking Description

This is a double-blind study with limited access to the randomization code.

Allocation

Randomized

Enrollment

24 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Active Comparator

Arm Type

Active Comparator

Arm Description

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

Arm Title

Experimental

Arm Type

Experimental

Arm Description

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

Intervention Type

Other

Intervention Name(s)

Omnipaque™ (iohexol) Injection

Intervention Description

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

Intervention Type

Other

Intervention Name(s)

CE-Iohexol

Intervention Description

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

Primary Outcome Measure Information:

Title

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

Description

Time Frame

48 hours

Title

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

Description

Time Frame

48 hours

Secondary Outcome Measure Information:

Title

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].

Description

Time Frame

30 days

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Keith Marschke, PhD

Organizational Affiliation

Ligand Pharmaceuticals

Official's Role

Study Director

Facility Information:

Facility Name

Syneos Health Clinique

City

Québec City

State/Province

Quebec

ZIP/Postal Code

G1P0A2

Country

Canada

12. IPD Sharing Statement

Learn more about this trial

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

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