Cardiac Safety Evaluation of P03277

NCT03657264 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: GDX-44-006
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Healthy Volunteers

Keywords

Gadolinium-based contrast agent; Cardiac safety; ECG; Gadopiclenol

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Change-from-baseline Mean Effect of Moxifloxacin on QT Interval Expressed as QTc According to Fridericia's Formula (∆QTcF)

  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.

• Predicted Value of ∆∆QTc at Cmax

  from 1 hour before any administration until 24 hours post-administration.

Study Arms (4)

Sequence 1

EXPERIMENTAL

The sequence of administration is: P/ScD/PC/CD Where: * P = Placebo (Nacl 0.9%) * CD = P03277 tested at 0.1 mmol/kg * ScD = P03277 tested at 0.3 mmol/kg * PC = Positive control (moxifloxacin 400 mg - per os).

Drug: P03277 0.1 mmol/kg; Drug: Moxifloxacin 400mg; Drug: NaCl 0.9%; Drug: P03277 0.3 mmol/kg

Sequence 2

EXPERIMENTAL

The sequence of administration is: CD/PC/ScD/P Where: * P = Placebo (Nacl 0.9%) * CD = P03277 tested at 0.1 mmol/kg * ScD = P03277 tested at 0.3 mmol/kg * PC = Positive control (moxifloxacin 400 mg - per os).

Drug: P03277 0.1 mmol/kg; Drug: Moxifloxacin 400mg; Drug: NaCl 0.9%; Drug: P03277 0.3 mmol/kg

Sequence 3

EXPERIMENTAL

The sequence of administration is: ScD/CD/P/PC Where: * P = Placebo (Nacl 0.9%) * CD = P03277 tested at 0.1 mmol/kg * ScD = P03277 tested at 0.3 mmol/kg * PC = Positive control (moxifloxacin 400 mg - per os).

Drug: P03277 0.1 mmol/kg; Drug: Moxifloxacin 400mg; Drug: NaCl 0.9%; Drug: P03277 0.3 mmol/kg

Sequence 4

EXPERIMENTAL

The sequence of administration is: PC/P/CD/ScD Where: * P = Placebo (Nacl 0.9%) * CD = P03277 tested at 0.1 mmol/kg * ScD = P03277 tested at 0.3 mmol/kg * PC = Positive control (moxifloxacin 400 mg - per os).

Drug: P03277 0.1 mmol/kg; Drug: Moxifloxacin 400mg; Drug: NaCl 0.9%; Drug: P03277 0.3 mmol/kg

Interventions

P03277 0.1 mmol/kg DRUG

Single intravenous bolus injection at 2 mL/sec

Also known as: Gadopiclenol

Sequence 1; Sequence 2; Sequence 3; Sequence 4

Moxifloxacin 400mg DRUG

One tablet per os

Sequence 1; Sequence 2; Sequence 3; Sequence 4

NaCl 0.9% DRUG

Single intravenous bolus injection at 2 mL/sec

Sequence 1; Sequence 2; Sequence 3; Sequence 4

P03277 0.3 mmol/kg DRUG

Single intravenous bolus injection at 2 mL/sec

Also known as: Gadopiclenol

Sequence 1; Sequence 2; Sequence 3; Sequence 4

Eligibility Criteria

• Age: 18 Years - 59 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

Sponsors & Collaborators

• Guerbet: lead

Study Sites (1)

Clinical Pharmacology unit, SGS-Life Science Service

Antwerp, 2060, Belgium

Location

MeSH Terms

Interventions

gadopiclenol; Moxifloxacin; Sodium Chloride

Intervention Hierarchy (Ancestors)

Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Results Point of Contact

• Title: Jing Hao, MD
• Organization: Guerbet

jing.hao@guerbet.com

+33145915000

Study Officials

• Frederic Vanhoutte, MD

  SGS Clinical Pharmacology Unit

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: DIAGNOSTIC
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Williams design for a 4\*4 cross over

Study Record Dates

• First Submitted: August 31, 2018
• First Posted: September 5, 2018
• Study Start: August 21, 2017
• Primary Completion: June 7, 2018
• Study Completion: June 7, 2018
• Last Updated: July 18, 2022
• Results First Posted: August 22, 2019

Record last verified: 2022-03

Locations

BE (1)