Pharmacokinetics, Safety, and Efficacy of Gadopiclenol in Pediatric Patients Aged 2 to 17 Years

Jurkiewicz, Elżbieta; Tsvetkova, Silvia; Grinberg, Anna; Pasquiers, Blaise

doi:10.1097/rli.0000000000000865

Cited by 13 publications

(26 citation statements)

References 23 publications

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“…The good safety profile of gadopiclenol has been previously highlighted in studies including healthy volunteers, 30,31 patients with CNS lesions, 11,30 pediatric patients with CNS and other body lesions, 32 and patients with renal impairment. 33 Results from this study showed a slightly lower rate of AEs related to gadopiclenol (4.9%) as compared with gadobutrol (6.9%), and the most frequent AEs were various types of reactions at the injection site for both GBCAs.…”

Section: Discussionmentioning

confidence: 92%

Efficacy and Safety of Gadopiclenol for Contrast-Enhanced MRI of the Central Nervous System

et al. 2022

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ObjectivesDeveloping new high relaxivity gadolinium-based contrast agents (GBCAs) for magnetic resonance imaging (MRI) allowing dose reduction while maintaining similar diagnostic efficacy is needed, especially in the context of gadolinium retention in tissues. This study aimed to demonstrate that contrast-enhanced MRI of the central nervous system (CNS) with gadopiclenol at 0.05 mmol/kg is not inferior to gadobutrol at 0.1 mmol/kg, and superior to unenhanced MRI.Materials and MethodsPICTURE is an international, randomized, double-blinded, controlled, cross-over, phase III study, conducted between June 2019 and September 2020. Adult patients with CNS lesions were randomized to undergo 2 MRIs (interval, 2–14 days) with gadopiclenol (0.05 mmol/kg) then gadobutrol (0.1 mmol/kg) or vice versa. The primary criterion was lesion visualization based on 3 parameters (border delineation, internal morphology, and contrast enhancement), assessed by 3 off-site blinded readers. Key secondary outcomes included lesion-to-background ratio, enhancement percentage, contrast-to-noise ratio, overall diagnostic preference, and adverse events.ResultsOf the 256 randomized patients, 250 received at least 1 GBCA administration (mean [SD] age, 57.2 [13.8] years; 53.6% women). The statistical noninferiority of gadopiclenol (0.05 mmol/kg) to gadobutrol (0.1 mmol/kg) was achieved for all parameters and all readers (n = 236, lower limit 95% confidence interval of the difference ≥−0.06, above the noninferiority margin [−0.35], P < 0.0001), as well as its statistical superiority over unenhanced images (n = 239, lower limit 95% confidence interval of the difference ≥1.29, P < 0.0001).Enhancement percentage and lesion-to-background ratio were higher with gadopiclenol for all readers (P < 0.0001), and contrast-to-noise ratio was higher for 2 readers (P = 0.02 and P < 0.0001). Three blinded readers preferred images with gadopiclenol for 44.8%, 54.4%, and 57.3% of evaluations, reported no preference for 40.7%, 21.6%, and 23.2%, and preferred images with gadobutrol for 14.5%, 24.1%, and 19.5% (P < 0.001).Adverse events reported after MRI were similar for gadopiclenol (14.6% of patients) and gadobutrol (17.6%). Adverse events considered related to gadopiclenol (4.9%) and gadobutrol (6.9%) were mainly injection site reactions, and none was serious.ConclusionsGadopiclenol at 0.05 mmol/kg is not inferior to gadobutrol at 0.1 mmol/kg for MRI of the CNS, confirming that gadopiclenol can be used at half the gadolinium dose used for other GBCAs to achieve similar clinical efficacy.

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Section: Discussionmentioning

confidence: 92%

Efficacy and Safety of Gadopiclenol for Contrast-Enhanced MRI of the Central Nervous System

et al. 2022

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“…23 A population pharmacokinetics approach was used to assess the pharmacokinetics of gadopiclenol in pediatric patients. 25 Only minor differences were reported between pediatric patients and adults with a median clearance ranging between 0.08 L/h/kg for the 12-to 17-yearold patients and 0.12 L/h/kg for the 2-to 6-year-old patients (vs 0.08 L/h/kg for adults). The median terminal half-life ranged between 1.29 hours for the 2-to 6-year-old patients and 1.77 hours for the 12to 17-year-old patients (vs 1.82 hours for adults).…”

Section: Pharmacokinetics Of Gadopiclenolmentioning

confidence: 88%

“…The pharmacokinetics of gadopiclenol was previously evaluated in 3 clinical studies including adult healthy volunteers, 23,24 adults with renal impairment, 23 and pediatric patients aged 2-17 years. 25 In adult healthy volunteers, the pharmacokinetic of gadopiclenol is linear, with a terminal elimination half-life of 1.5 to 2 hours. Gadopiclenol is distributed within the extracellular water compartment and has a distribution volume consistent with this distribution characteristics (ie, 182-254 mL/kg).…”

Section: Pharmacokinetics Of Gadopiclenolmentioning

confidence: 99%

A Comprehensive Overview of the Efficacy and Safety of Gadopiclenol: A New Contrast Agent for MRI of the CNS and Body

Hao,

Pitrou,

Bourrinet

2023

Invest Radiol

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This review describes the pharmacokinetics, efficacy, and safety of gadopiclenol, a new macrocyclic gadolinium-based contrast agent (GBCA) recently approved by the Food and Drug Administration at the dose of 0.05 mmol/kg. Gadopiclenol is a high relaxivity contrast agent that shares similar pharmacokinetic characteristics with other macrocyclic GBCAs, including a predominant renal excretion. In pediatric patients aged 2–17 years, the pharmacokinetic parameters (assessed through a population pharmacokinetics model) were comparable to those observed in adults, indicating no need for age-based dose adjustment. For contrast-enhanced magnetic resonance imaging (MRI) of the central nervous system (CNS) and body indications, gadopiclenol at 0.05 mmol/kg was shown to be noninferior to gadobutrol at 0.1 mmol/kg in terms of 3 lesion visualization parameters (ie, lesion border delineation, internal morphology, and contrast enhancement). Moreover, for contrast-enhanced MRI of the CNS, compared with gadobenate dimeglumine at 0.1 mmol/kg, gadopiclenol exhibited superior contrast-to-noise ratio at 0.1 mmol/kg and comparable contrast-to-noise ratio at 0.05 mmol/kg. A pooled safety analysis of 1047 participants showed a favorable safety profile for gadopiclenol. Comparative studies showed that the incidence and nature of adverse drug reactions with gadopiclenol were comparable to those observed with other GBCAs. Importantly, no significant safety concerns were identified in pediatric and elderly patients, as well as in patients with renal impairment. Overall, these findings support the clinical utility and safety of gadopiclenol for MRI in adult and pediatric patients aged 2 years and older in CNS and body indications.

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“…It has been approved with a black box warning regarding the increases risk for nephrogenic systemic fibrosis in patients with impaired elimination, such as encountered in severe kidney diseases. Clinical trials demonstrated that gadopiclenol has a good safety profile (Hao et al 2019 ; Jurkiewicz et al 2022 ).…”

Section: Othermentioning

confidence: 99%

A year in pharmacology: new drugs approved by the US Food and Drug Administration in 2022

Kaykı-Mutlu

Aksoyalp

Wojnowski

et al. 2023

Naunyn-Schmiedeberg's Arch Pharmacol

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While new drug approvals by the U.S. Food and Drug Administration (FDA) had remained stable or even increased in the first 2 years of the COVID-19 pandemic, the 37 newly approved drugs in 2022 are considerably less than the 53 and 50 new drugs approved in 2020 and 2021, respectively, and less than the rolling 10-year average of 43. As in previous years of this annual review, we assign these new drugs to one of three levels of innovation: first drug against a condition (“first-in-indication”), first drug using a novel molecular mechanism (“first-in-class”), and “next-in-class,” i.e., a drug using an already exploited molecular mechanism. We identify two “first-in-indication” (ganaxolon and teplizumab), 20 (54%) “first-in-class,” and 17 (46%) “next-in-class” drugs. By treatment area, rare diseases and cancer drugs were once again the most prevalent (partly overlapping) therapeutic areas. Other continuing trends were the use of accelerated regulatory approval pathways and the reliance on biopharmaceuticals (biologics).

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Pharmacokinetics, Safety, and Efficacy of Gadopiclenol in Pediatric Patients Aged 2 to 17 Years

Cited by 13 publications

References 23 publications

Efficacy and Safety of Gadopiclenol for Contrast-Enhanced MRI of the Central Nervous System

Efficacy and Safety of Gadopiclenol for Contrast-Enhanced MRI of the Central Nervous System

A Comprehensive Overview of the Efficacy and Safety of Gadopiclenol: A New Contrast Agent for MRI of the CNS and Body

A year in pharmacology: new drugs approved by the US Food and Drug Administration in 2022

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