Pharmacokinetics and Safety of Gadopiclenol in Japanese Healthy Volunteers

NCT04906005 | Completed Phase 1

• 2 other identifiers: GDX-44-013jRCT2071210029
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

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.

Conditions

Pharmacokinetics

Outcome Measures

Primary Outcomes (9)

• 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

Study Arms (2)

gadopiclenol

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

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

Interventions

gadopiclenol DRUG

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

gadopiclenol

Placebo DRUG

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

Placebo

Eligibility Criteria

• Age: 20 Years - 59 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Guerbet: lead

Study Sites (1)

Hataka clinic

Fukuoka, Japan

Location

MeSH Terms

Interventions

gadopiclenol

Study Officials

• Jing Hao

  Guerbet

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: 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.
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 25, 2021
• First Posted: May 28, 2021
• Study Start: May 10, 2021
• Primary Completion: July 27, 2021
• Study Completion: July 27, 2021
• Last Updated: October 7, 2021

Record last verified: 2021-05

Locations

JP (1)