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

Phase 1
Completed
Conditions
Healthy Volunteers
Brain Lesion
Interventions
Drug: Placebo
Registration Number
NCT03603106
Lead Sponsor
Guerbet
Brief Summary

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

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
142
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).
Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
SEQUENTIAL
Arm && Interventions
GroupInterventionDescription
Part I (Phase I)PlaceboIn 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.
Part II (Phase IIA)P03277In each dose group (0.05, 0.075, 0.1 and 0.2 mmol/kg), all 3 patients received one single intravenous administration of P03277.
Part I (Phase I)P03277In 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.
Primary Outcome Measures
NameTimeMethod
Pharmacokinetic (PK) Parameter CmaxFrom baseline (30 minutes before injection) to 24 hours post-injection

Cmax = maximum concentration measured. Blood samples were taken to assess the P03277 concentration.

PK Parameter T1/2From baseline (30 minutes before injection) to 24 hours post-injection

T1/2 = terminal elimination half-life of the compound. Blood samples were taken to assess the P03277 concentration.

PK Parameter ClFrom baseline (30 minutes before injection) to 24 hours post-injection

Cl = total clearance. Blood samples were taken to assess the P03277 concentration.

PK Parameter VdFrom baseline (30 minutes before injection) to 24 hours post-injection

Vd = volume of distribution. Blood samples were taken to assess the P03277 concentration.

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (1)

Clinical Pharmacology unit, SGS Life Science Services

🇧🇪

Antwerpen, Belgium

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