Pharmacokinetics and Safety of Gadopiclenol in Japanese Healthy Volunteers

A Randomized, Double Blind, Placebo-Controlled, Single Ascending Dose Trial to Assess the Pharmacokinetics and Safety of Gadopiclenol in Japanese Healthy Volunteers Phase I Clinical Trial

This single center, single ascending dose, double blind, randomized, placebo-controlled phase I trial will include male and female Japanese healthy volunteers. Within a 4-week run-in period before inclusion in the trial, healthy volunteers will be checked for inclusion/non-inclusion criteria and will then be randomized and administered with gadopiclenol or placebo. For each healthy volunteer, there will be a confinement period of one night before the inclusion visit and 2 days post administration at the clinical unit. The healthy volunteers will return to the clinical unit for safety visit 7 days after study product administration.

In each dose group, 6 healthy volunteers (3 male and 3 female) will receive gadopiclenol and 3 healthy volunteers (2M/1F or 1M/2F) will receive placebo (physiological saline solution, 0.9% sodium chloride) in one single intravenous administration.

Dose escalation from one group to the next group will be sequential and will be allowed only if the clinical and biological safety of all healthy volunteers from the previous tested dose is acceptable. The decision will be made by a Trial Safety Review Board (TSRB), consisting in members of Guerbet team and the principal investigator.

Study Overview

• Status: Completed
• Conditions: Pharmacokinetics
• Intervention / Treatment: Drug: gadopiclenol; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Fukuoka, Japan
    • Hataka clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 59 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• A Japanese healthy volunteer is defined as being born in Japan and having both parents and four grandparents (maternal and paternal) who are ethnically Japanese and having Japanese lifestyle, including diet, as determined by participant's verbal report.
• Good health status as determined by investigator according to past medical history, clinical examination, including 12 lead ECG, vital signs (blood pressure, pulse rate, respiratory rate and body temperature) and laboratory tests at screening and inclusion.

Exclusion Criteria:

• Pregnant or breast-feeding female volunteer.
• Having acute or chronic renal insufficiency, defined as an eGFR (estimated Glomerular Filtration Rate) <90mL/min/1.73 m2, calculated by using the Japanese coefficient-modified CKD-EPI formula.
• With known contra-indication(s) to the use or with known sensitivity to one of the products under investigation or to drugs from a similar pharmaceutical class.
• With known history of severe allergic or anaphylactic reactions to any allergen including drugs and contrast agents.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: gadopiclenol; Dose per administration: dose/volume of gadopiclenol to be administered will be calculated based on patient's weight at the dose of 0.025; 0.05 or 0.1 mmol/kg BW (depending on each group). 6 volunteers will receive gadopiclenol per group	Drug: gadopiclenol; administration by intravenous (IV) bolus injection at 2 mL/s rate without dilution, followed by a saline flush of at least 5 mL at the same rate to ensure complete injection of the contrast agent.The gadopiclenol administration is performed by power injecto
Placebo Comparator: Placebo; Dose per administration: similar dose (Volume/weight) as the one used for Gadopiclenol in the considered group. 3 volunteers will receive gadopiclenol per group	Drug: Placebo; intravenous (IV) bolus injection at 2 mL/s, followed by a saline flush of at least 5 mL to be in the same conditions as for gadopiclenol administration.The gadopiclenol administration is performed by power injector

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax	Maximum concentrations measured, value taken directly from the observed concentration-time profiles	from baseline (30 minutes before injection) to 24hours post injection
Tmax	Time corresponding to Cmax	from baseline (30 minutes before injection) to 24hours post injection
AUC 0-inf	Area Under the observed concentration-time Curve from zero (time of drug administration) to infinity with extrapolation of the terminal phase. It will be obtained as follows: AUC 0-inf = AUC 0-T last + (Clast / β)	from baseline (30 minutes before injection) to 24hours post injection
t 1/2β	Terminal elimination half-life of gadopiclenol calculated as follows: t 1/2β = ln 2 / β	from baseline (30 minutes before injection) to 24hours post injection
AUC extrap%	Percentage of extrapolation of AUC from the last observation (Tlast) to infinity calculated as follows: Percentage of extrapolation of AUC from the last observation (Tlast) to infinity calculated as follows: Percentage of extrapolation of AUC from the last observation (Tlast) to infinity calculated as follows:	from baseline(30 minutes before injection) to 24hours post injection
CLT	Total Clearance, calculated as CLT = Dose /AUC 0-inf	from baseline (30 minutes before injection) to 24hours post injection
Vdβ	Volume of distribution, calculated as Vdβ = Dose / (AUC 0-inf x β)	from baseline (30 min before injection) to 24h post injection
Ae	Total amount of gadopiclenol excreted in urine	Before administration and during intervals 0-6hours, 6-24hours and 24-48hours after gadopiclenol administration
CLR	Renal clearance, calculated as CLR = Ae / AUC 0-inf	Before administration and during intervals0-6hours, 6-24hours and 24-48hours after gadopiclenol administration

Collaborators and Investigators

• Sponsor: Guerbet
• Investigators: Study Chair: Jing Hao, Guerbet

Study record dates

Study Major Dates

• Study Start (Actual): May 10, 2021
• Primary Completion (Actual): July 27, 2021
• Study Completion (Actual): July 27, 2021

Study Registration Dates

• First Submitted: May 25, 2021
• First Submitted That Met QC Criteria: May 25, 2021
• First Posted (Actual): May 28, 2021

Study Record Updates

• Last Update Posted (Actual): October 7, 2021
• Last Update Submitted That Met QC Criteria: October 6, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Other Study ID Numbers: GDX-44-013; jRCT2071210029 (Registry Identifier: jRCT (Japan Registry of Clinical Trials))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No