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

Guerbet

Status and phase: Completed; Phase 2; Phase 1

Conditions: Healthy Volunteers; Brain Lesion

Treatments: Drug: P03277; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT03603106

2013-004428-12 (EudraCT Number)

GDX-44-003

Details and patient eligibility

About

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.

Full 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.

Enrollment: 142 patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

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).

Trial design

Primary purpose: Diagnostic

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Triple Blind

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142 participants in 2 patient groups

Part I (Phase I)

Experimental group

Description:

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.

Treatment:

Drug: Placebo

Drug: P03277

Part II (Phase IIA)

Experimental group

Description:

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.

Treatment:

Drug: P03277