The aim of this study was to determine a safe and effective dose of gadopiclenol,
a new high relaxivity macrocyclic gadolinium-based contrast agent. Based on the contrast-to-noise
ratio (CNR) as primary criterion, this new agent was compared with gadobenate dimeglumine
in patients with contrast-enhancing central nervous system lesions.This phase IIb
international, multicenter, double-blind, randomized, controlled, parallel dose groups,
and cross-over study included adult patients with known or highly suspected lesions
with disrupted blood-brain barrier. Patients were randomized to 1 of 4 doses of gadopiclenol
(0.025, 0.05, 0.1, 0.2 mmol/kg) and to 1 series of 2 magnetic resonance imaging scans:
gadopiclenol then gadobenate dimeglumine at 0.1 mmol/kg or vice versa. The qualitative
and quantitative efficacy evaluations were performed by 3 independent off-site blinded
readers. Adverse events were monitored up to 1 day after second magnetic resonance
imaging.The study population included 272 patients (58.5% females) with a mean (SD)
age of 53.8 (13.6) years. The superiority of gadopiclenol over gadobenate dimeglumine
was statistically demonstrated at 0.2 and 0.1 mmol/kg for all readers with an increase
in CNR of more than 30% (P ≤ 0.0007). At 0.05 mmol/kg, gadopiclenol showed a CNR of
similar magnitude as gadobenate dimeglumine at 0.1 mmol/kg, with no statistically
significant difference. Similar results were obtained for lesion-to-brain ratio and
contrast enhancement percentage, as secondary criteria. The relationship between CNR
and dose of gadopiclenol was linear for all readers. Mean scores for lesion visualization
variables, particularly lesion contrast enhancement, tended to be higher with gadopiclenol
at 0.1 and 0.2 mmol/kg compared with gadobenate dimeglumine. All 3 readers mainly
expressed an overall diagnostic preference for images with gadopiclenol at 0.1 mmol/kg
(45.3%, 50.9%, or 86.8% of images) or expressed no preference (49.1%, 49.1%, or 9.4%,
respectively), whereas preference for images with gadobenate dimeglumine was reported
by 2 readers for 3.8% and 5.7% of the images. Predominantly, no preference was expressed
when comparing images with gadopiclenol at 0.05 mmol/kg to those with gadobenate dimeglumine.Rates
of adverse reactions were comparable for gadopiclenol (11.7%) and gadobenate dimeglumine
(12.1%). Changes from baseline of more than 25% in serum creatinine and estimated
glomerular filtration rate occurred in less than 2% of patients equally for gadopiclenol
and gadobenate dimeglumine. Changes from baseline for the values of blood urea nitrogen
and cystatin C were also similar between gadopiclenol and gadobenate dimeglumine.
No safety concerns were detected on centralized electrocardiography readings.Between
the doses of 0.025 and 0.2 mmol/kg of gadopiclenol, the increase in CNR is linear.
Compared with gadobenate dimeglumine at 0.1 mmol/kg, the doses of 0.05 and 0.1 mmol/kg
of gadopiclenol gave similar or significantly greater contrast enhancement, respectively,
and thus both doses can be considered for future phase III studies.
