Pharmacokinetics and Safety of Gadopiclenol in Japanese Healthy Volunteers

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Pharmacokinetics

Intervention / Treatment
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* Drug: gadopiclenol
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 59 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: gadopiclenol<br>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<br>* 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<br>|
| Placebo Comparator: Placebo<br>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<br>* 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<br>|

What is the study measuring?
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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 |