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

• ClinicalTrials.gov Identifier: NCT03603106
• Recruitment Status: Completed
• First Posted: July 27, 2018
• Results First Posted: July 12, 2019
• Last Update Posted: May 14, 2021
• Sponsor: Guerbet
• Information provided by (Responsible Party): Guerbet

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Healthy Volunteers; Brain Lesion	Drug: P03277; Drug: Placebo	Phase 1; Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 142 participants
• Allocation: Randomized
• Intervention Model: Sequential Assignment

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.

• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Diagnostic
• Official Title: Assessment of Pharmacokinetics, Pharmacodynamics Profile and Tolerance of P03277 in Healthy Subjects and Patients With Brain Lesions
• Actual Study Start Date: November 25, 2013
• Actual Primary Completion Date: April 17, 2015
• Actual Study Completion Date: April 17, 2015

Arms and Interventions

Arm	Intervention/treatment
Experimental: Part I (Phase I); 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; 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.; Other Name: Gadopiclenol; Drug: Placebo; 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.; Other Name: NaCl 0.9%
Experimental: Part II (Phase IIA); 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; 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.; Other Name: Gadopiclenol

Outcome Measures

Primary Outcome Measures :

1. Pharmacokinetic (PK) Parameter Cmax [ Time Frame: From baseline (30 minutes before injection) to 24 hours post-injection ]
   Cmax = maximum concentration measured. Blood samples were taken to assess the P03277 concentration.
2. PK Parameter T1/2 [ Time Frame: From 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.
3. PK Parameter Cl [ Time Frame: From baseline (30 minutes before injection) to 24 hours post-injection ]
   Cl = total clearance. Blood samples were taken to assess the P03277 concentration.
4. PK Parameter Vd [ Time Frame: From baseline (30 minutes before injection) to 24 hours post-injection ]
   Vd = volume of distribution. Blood samples were taken to assess the P03277 concentration.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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).

Contacts and Locations

Locations

Belgium

Clinical Pharmacology unit, SGS Life Science Services

Antwerpen, Belgium, 2060

Sponsors and Collaborators

Guerbet

Investigators

• Principal Investigator: Wouter Haazen, MD; SGS Clinical Pharmacology Unit

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Hao J, Bourrinet P, Desché 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.

• Responsible Party: Guerbet
• ClinicalTrials.gov Identifier: NCT03603106
• Other Study ID Numbers: GDX-44-003; 2013-004428-12 ( EudraCT Number )
• First Posted: July 27, 2018
• Results First Posted: July 12, 2019
• Last Update Posted: May 14, 2021
• Last Verified: May 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No