Pharmacokinetics
Conditions
Brief 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.
Interventions
DRUGgadopiclenol
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
DRUGPlacebo
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
Sponsors
Guerbet
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
To ensure that administration of the IMP is carried out under double-blind conditions, an unblinded team (nurse, technician or physician) will be responsible for preparing and administrating the IMP(s). This person will ensure non-disclosure of information.
Eligibility
Sex/Gender
ALL
Age
20 Years to 59 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cmax | from baseline (30 minutes before injection) to 24hours post injection | Maximum concentrations measured, value taken directly from the observed concentration-time profiles |
| Tmax | from baseline (30 minutes before injection) to 24hours post injection | Time corresponding to Cmax |
| AUC 0-inf | from baseline (30 minutes before injection) to 24hours post injection | 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) |
| t 1/2β | from baseline (30 minutes before injection) to 24hours post injection | Terminal elimination half-life of gadopiclenol calculated as follows: t 1/2β = ln 2 / β |
| AUC extrap% | from baseline(30 minutes before injection) to 24hours post injection | 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: |
| CLT | from baseline (30 minutes before injection) to 24hours post injection | Total Clearance, calculated as CLT = Dose /AUC 0-inf |
| Vdβ | from baseline (30 min before injection) to 24h post injection | Volume of distribution, calculated as Vdβ = Dose / (AUC 0-inf x β) |
| Ae | Before administration and during intervals 0-6hours, 6-24hours and 24-48hours after gadopiclenol administration | Total amount of gadopiclenol excreted in urine |
| CLR | Before administration and during intervals0-6hours, 6-24hours and 24-48hours after gadopiclenol administration | Renal clearance, calculated as CLR = Ae / AUC 0-inf |
Countries
Japan
Outcome results
None listed