Pharmacokinetics, Pharmacodynamics Profile and Tolerance of P03277 in Healthy Subjects and Patients With Brain Lesions

Assessment of Pharmacokinetics, Pharmacodynamics Profile and Tolerance of P03277 in Healthy Subjects and Patients With Brain Lesions

The primary objective of this study was to evaluate the safety (clinical and biological) and pharmacokinetics (plasma and urine) profile of P03277 following single administration at ascending dose levels in healthy subjects.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers; Brain Lesion
• Intervention / Treatment: Drug: P03277; Drug: Placebo

Detailed Description

This single-center, single ascending dose, phase I/IIa study was divided into 2 parts, involving both healthy subjects and patients with brain lesions:

• Study Part I included healthy subjects: double-blind, randomized, placebo control;
• Study Part II included patients with brain lesions: open-label.

In Part I, the following 6 dosing groups were investigated:

• Group 1: 0.025 mmol/kg
• Group 2: 0.05 mmol/kg
• Group 3: 0.075 mmol/kg
• Group 4: 0.1 mmol/kg
• Group 5: 0.2 mmol/kg
• Group 6: 0.3 mmol/kg

Healthy subjects were included and were then administered with P03277 or placebo and were to undergo MRI examination according to the randomization scheme.

In Part II, the following 4 doses groups were investigated:

• Group 7: 0.05 mmol/kg
• Group 8: 0.075 mmol/kg
• Group 9: 0.1 mmol/kg
• Group 10: 0.2 mmol/kg

Patients with brain lesions were included and were then administered with P03277 and underwent MRI examination.

• Study Type: Interventional
• Enrollment (Actual): 142
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Antwerpen, Belgium, 2060
    • Clinical Pharmacology unit, SGS Life Science Services

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Part I: Subjects between 18 and 45 years old (inclusive), with a body mass index (BMI) of 18 to 30 kg/m² (exclusive) and in a good health.
• Part II: Patients 18 years old and older and having at least one brain lesion with a disruption of the blood brain barrier (BBB) and/or with abnormal vascularity in the brain. This/these lesion(s) must have been detected by previous imaging evaluation (Computed Tomography or MRI).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part I (Phase I); In each dose group (0.025, 0.05, 0.075, 0.1, 0.2 and 0.3 mmol/kg), 9 healthy subjects were to be included: 6 subjects received P03277 and 3 subjects received placebo in one single intravenous administration.	Drug: P03277; Part I: P03277 was administered intravenously with a flow rate ranging from 0.5 to 2 mL/s. Part II: P03277 was administered intravenously with a flow rate of 2 mL/s.; Other Names: Gadopiclenol; Drug: Placebo; Part I: Placebo was administered intravenously with a flow rate ranging from 0.5 to 2 mL/s. Part II: Placebo was administered intravenously with a flow rate of 2 mL/s.; Other Names: NaCl 0.9%
Experimental: Part II (Phase IIA); In each dose group (0.05, 0.075, 0.1 and 0.2 mmol/kg), all 3 patients received one single intravenous administration of P03277.	Drug: P03277; Part I: P03277 was administered intravenously with a flow rate ranging from 0.5 to 2 mL/s. Part II: P03277 was administered intravenously with a flow rate of 2 mL/s.; Other Names: Gadopiclenol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic (PK) Parameter Cmax	Cmax = maximum concentration measured. Blood samples were taken to assess the P03277 concentration.	From baseline (30 minutes before injection) to 24 hours post-injection
PK Parameter T1/2	T1/2 = terminal elimination half-life of the compound. Blood samples were taken to assess the P03277 concentration.	From baseline (30 minutes before injection) to 24 hours post-injection
PK Parameter Cl	Cl = total clearance. Blood samples were taken to assess the P03277 concentration.	From baseline (30 minutes before injection) to 24 hours post-injection
PK Parameter Vd	Vd = volume of distribution. Blood samples were taken to assess the P03277 concentration.	From baseline (30 minutes before injection) to 24 hours post-injection

Collaborators and Investigators

• Sponsor: Guerbet
• Investigators: Principal Investigator: Wouter Haazen, MD, SGS Clinical Pharmacology Unit

Publications and helpful links

General Publications

• Hao J, Bourrinet P, Desche P. Assessment of Pharmacokinetic, Pharmacodynamic Profile, and Tolerance of Gadopiclenol, A New High Relaxivity GBCA, in Healthy Subjects and Patients With Brain Lesions (Phase I/IIa Study). Invest Radiol. 2019 Jul;54(7):396-402. doi: 10.1097/RLI.0000000000000556.

Study record dates

Study Major Dates

• Study Start (Actual): November 25, 2013
• Primary Completion (Actual): April 17, 2015
• Study Completion (Actual): April 17, 2015

Study Registration Dates

• First Submitted: July 16, 2018
• First Submitted That Met QC Criteria: July 26, 2018
• First Posted (Actual): July 27, 2018

Study Record Updates

• Last Update Posted (Actual): May 14, 2021
• Last Update Submitted That Met QC Criteria: May 12, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Other Study ID Numbers: GDX-44-003; 2013-004428-12 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No