Clinical trial NCT03603106: Pharmacokinetics, Pharmacodynamics Profile and Tolerance of P03277 in Healthy Subjects and Patients With Brain Lesions
Official title: Assessment of Pharmacokinetics, Pharmacodynamics Profile and Tolerance of P03277 in Healthy Subjects and Patients With Brain Lesions
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Healthy Volunteers
Brain Lesion
Lead sponsor: Guerbet
Sponsor class: INDUSTRY
First posted: 2018-07-27
Enrollment: 142
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention 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.
Primary purpose: DIAGNOSTIC

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.

Eligibility 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).

Primary outcomes:
measure: Pharmacokinetic (PK) Parameter Cmax
timeFrame: From baseline (30 minutes before injection) to 24 hours post-injection
measure: PK Parameter T1/2
timeFrame: From baseline (30 minutes before injection) to 24 hours post-injection
measure: PK Parameter Cl
timeFrame: From baseline (30 minutes before injection) to 24 hours post-injection
measure: PK Parameter Vd
timeFrame: From baseline (30 minutes before injection) to 24 hours post-injection
Secondary outcomes:
Other outcomes:
Locations:
city: Antwerpen
country: Belgium
facility: Clinical Pharmacology unit, SGS Life Science Services
Study officials:
affiliation: SGS Clinical Pharmacology Unit
name: Wouter Haazen, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hao J, Bourrinet P, Desche P. Assessment of Pharmacokinetic, Pharmacodynamic Profile, and Tolerance of Gadopiclenol, A New High Relaxivity GBCA, in Healthy Subjects and Patients With Brain Lesions (Phase I/IIa Study). Invest Radiol. 2019 Jul;54(7):396-402. doi: 10.1097/RLI.0000000000000556.