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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Healthy Volunteers, Brain Lesion

Intervention / Treatment
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* Drug: P03277
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Part I: Sequential administration within each group of healthy subjects was established. Part II: The administration to patients within the same day was sequential to ensure the well-being of the patients. At least a 1-hour interval between 2 administrations had to be respected.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part I (Phase I)<br>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<br>* 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.<br>* Other names: Gadopiclenol;Drug: Placebo<br>* 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.<br>* Other names: NaCl 0.9%;|
| Experimental: Part II (Phase IIA)<br>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<br>* 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.<br>* Other names: Gadopiclenol;|

What is the study measuring?
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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 |