P03277 Dose Finding Study in Central Nervous System (CNS) Magnetic Resonance Imaging (MRI)

Two subsets of subjects were included in the study:

• The subset 1 included the first randomized subject of each study center. Subjects were randomly assigned in a 1:1 ratio to receive 0.05 or 0.1 mmol/kg BW of P03277 and 0.1 mmol/kg BW of gadobenate dimeglumine.
• Subset 2 was composed of all subjects (except the first one of each study center) selected by the study center. Subjects were randomly assigned in a 1:1:1:1 ratio to receive 0.025, 0.05, 0.1 or 0.2 mmol/kg BW of P03277 and 0.1 mmol/kg BW of gadobenate dimeglumine.

During the course of the study, two MRIs were obtained from each subject: one unenhanced and P03277-enhanced MRI; and one unenhanced and gadobenate dimeglumine-enhanced MRI. MRI images were evaluated off-site by 3 independent blinded readers for the primary endpoint (CNR).

Inclusion criteria

• Female or male adult subjects, with known or highly suspected focal areas of disrupted Blood Brain Barrier including at least one expected enhancing lesion of minimum 5 mm (long axis). This lesion had been detected on a previous imaging procedure (computerized Tomography [CT] or MRI).
• Subject scheduled for a routine contrast-enhanced MRI examination of Central Nervous System for clinical reasons and agreeing to have a second contrast-enhanced MRI examination for the purpose of the study.

Exclusion criteria

• Subject presenting with acute or chronic Grade III (at least) renal insufficiency, defined as an estimated Glomerular Filtration Rate (eGFR) <60 mL/min/1.73 m² based on one eGFR assessment performed the day of the MRI prior to the first contrast agent injection.