Cardiac Safety Evaluation of P03277

Healthy Volunteers Clinical Trial

Official title:

Thorough QT/QTc Study to Assess the Electrocardiographic Safety of a New Gadolinium-based Contrast Agent P03277 in Healthy Volunteers

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03657264
• Other study ID #: GDX-44-006
• Status: Completed
• Phase: Phase 1
• Start date: August 21, 2017
• Est. completion date: June 7, 2018

Study information

• Verified date: March 2022
• Source: Guerbet
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The study is a Phase I, Single center, Randomized, Cross-over Double-blind Placebo-controlled and Open-label Positive-controlled (moxifloxacin) in healthy volunteers.

The primary objective is to assess the cardiac safety after administration of P03277 to 48 healthy volunteers at dose of 0.1 mmol/kg (anticipated clinical dose) and 0.3 mmol/kg (supra-clinical dose) by evaluating the QT and QTc intervals.

Description:

Each subjects will be administered with 4 products (P03277 at the 2 different doses, placebo and moxifloxacin) in a 4*4 cross over sequence balanced for first order carry over effect. Twelve subjects will be assigned to each sequence (6 males and 6 females). The volunteers will be enrolled sequentially by cohort of 8 subjects.

ECG measurements will be compared with ECG parameters collected after administration of placebo (Nacl 0.9%). The test sensitivity will be assessed using a positive control (moxifloxacin 400 mg per os) known to induce delays in QT intervals.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 48
• Est. completion date: June 7, 2018
• Est. primary completion date: June 7, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 59 Years

Eligibility

Inclusion Criteria:

• Subject assessed as healthy by a comprehensive clinical assessment (detailed medical history and complete physical examination)

• Subject with a Body Mass Index (BMI) > 19 kg/m² and < 28 kg/m² and a weight at least of 40 kg for female and 50 kg for male and at maximum of 100 kg

Exclusion Criteria:

-

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

Drug:
• P03277 0.1 mmol/kg
Single intravenous bolus injection at 2 mL/sec
• Moxifloxacin 400mg
One tablet per os
• NaCl 0.9%
Single intravenous bolus injection at 2 mL/sec
• P03277 0.3 mmol/kg
Single intravenous bolus injection at 2 mL/sec

Locations

Country	Name	City	State
Belgium	Clinical Pharmacology unit, SGS-Life Science Service	Antwerpen

Sponsors (1)

Lead Sponsor	Collaborator
Guerbet

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change-from-baseline Mean Effect of P03277 on QT Interval Expressed as QTc According to Fridericia's Formula (?QTcF)	Each subject was monitored with a 12-lead Holter electrocardiogram (ECG). The study had to show that both 0.1 and 0.3 mmol/kg doses of P03277 do not increase the QT interval corrected by Fridericia formula (QTcF).; The study is successful if the difference between each of the two doses of P03277 and placebo for the largest mean change from baseline for the QTcF is lower than 10 milliseconds. The baseline was defined as the mean of the 3 triplicates ECG measured within 1 hour before each product administration.	from 1 hour before any administration until 24 hours post-administration at the following timepoints: -1 hour, 5 min, 10 min, 20 min, 30 min, 1 hour, 1.5 hours, 2 hours, 3 hours, 4 hours, 8 hours, 24 hours.
Secondary	Change-from-baseline Mean Effect of Moxifloxacin on QT Interval Expressed as QTc According to Fridericia's Formula (?QTcF)	Each subject was monitored with a 12-lead Holter electrocardiogram (ECG). The assay sensitivity was assessed through this outcome. The difference between the positive control (moxifloxacin) and placebo for the largest mean change from baseline for the QTcF had to be greater than 5 milliseconds for at least one time point. The baseline was defined as the mean of the 3 triplicates ECG measured within 1 hour before each product administration.	from 1 hour before any administration until 4 hours post-administration at the following timepoints: -1 hour, 1 hour, 1.5 hours, 2 hours, 3 hours, 4 hours.
Secondary	Predicted Value of ??QTc at Cmax	Concentration-response relationship was investigated between ?QTc and P03277 concentrations using a mixed model approach. Plasma concentration of P03277 was measured at the same timepoints as ECG measurements.	from 1 hour before any administration until 24 hours post-administration.