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.

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.

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).