Pharmacokinetics and Safety of Gadopiclenol in Japanese Healthy Volunteers

Pharmacokinetics Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04906005
• Other study ID #: GDX-44-013
• Secondary ID: jRCT2071210029
• Status: Completed
• Phase: Phase 1
• Start date: May 10, 2021
• Est. completion date: July 27, 2021

Study information

• Verified date: May 2021
• Source: Guerbet
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 27
• Est. completion date: July 27, 2021
• Est. primary completion date: July 27, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 20 Years to 59 Years

Eligibility

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.

Related Conditions & MeSH terms

• Pharmacokinetics

Intervention

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
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

Locations

Country	Name	City	State
Japan	Hataka clinic	Fukuoka

Sponsors (1)

Lead Sponsor	Collaborator
Guerbet

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cmax	Maximum concentrations measured, value taken directly from the observed concentration-time profiles	from baseline (30 minutes before injection) to 24hours post injection
Primary	Tmax	Time corresponding to Cmax	from baseline (30 minutes before injection) to 24hours post injection
Primary	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 / ß)	from baseline (30 minutes before injection) to 24hours post injection
Primary	t 1/2ß	Terminal elimination half-life of gadopiclenol calculated as follows: t 1/2ß = ln 2 / ß	from baseline (30 minutes before injection) to 24hours post injection
Primary	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
Primary	CLT	Total Clearance, calculated as CLT = Dose /AUC 0-inf	from baseline (30 minutes before injection) to 24hours post injection
Primary	Vdß	Volume of distribution, calculated as Vdß = Dose / (AUC 0-inf x ß)	from baseline (30 min before injection) to 24h post injection
Primary	Ae	Total amount of gadopiclenol excreted in urine	Before administration and during intervals 0-6hours, 6-24hours and 24-48hours after gadopiclenol administration
Primary	CLR	Renal clearance, calculated as CLR = Ae / AUC 0-inf	Before administration and during intervals0-6hours, 6-24hours and 24-48hours after gadopiclenol administration