A Phase IIa: single ascending dose safety, tolerability and pharmacokinetic study of NicaPlant® in aneurysmal subarachnoid haemorrhage patients undergoing aneurysm clipping

开始日期2018-02-19

申办/合作机构

BIT Pharma GmbH

100 项与 NicaPlant 相关的临床结果

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100 项与 NicaPlant 相关的转化医学

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100 项与 NicaPlant 相关的专利（医药）

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项与 NicaPlant 相关的文献（医药）

2023-01-01·Brain and Spine

A randomized, single ascending dose safety, tolerability and pharmacokinetics study of NicaPlant® in aneurysmal subarachnoid hemorrhage patients undergoing clipping

Article

作者: Wolf, Stefan ; Gmeiner, Matthias ; Vajkoczy, Peter ; Gruber, Andreas ; Kerschbaumer, Johannes ; Petr, Ondra ; Gollwitzer, Maria ; Stefanits, Harald ; Freyschlag, Christian Franz ; Gempt, Jens ; Meyer, Bernhard ; Bendszus M, Martin ; Breitenbach J, Joerg ; Hecht, Nils ; Thomé, Claudius ; Adage, Tiziana ; Wostrack, Maria ; Wessels, Lars

IntroductionAneurysmal subarachnoid hemorrhage (aSAH) is associated with high morbidity and mortality. Post-hemorrhagic vasospasm with neurological deterioration is a major concern in this context. NicaPlant®, a modified release formulation of the calcium channel blocker nicardipine, has shown vasodilator efficacy preclinically and a similar formulation known as NPRI has shown anti-vasospasm activity in aSAH patients under compassionate use.Research questionThe study aimed to assess pharmacokinetics and pharmacodynamics of NicaPlant® pellets to prevent vasospasm after clip ligation in aSAH.Material and methodsIn this multicenter, controlled, randomized, dose escalation trial we assessed the safety and tolerability of NicaPlant®. aSAH patients treated by clipping were randomized to receive up to 13 NicaPlant® implants, similarly to the dose of NPRIs previous used, or standard of care treatment.ResultsTen patients across four dose groups were treated with NicaPlant® (3-13 implants) while four patients received standard of care. 45 non-serious and 13 serious adverse events were reported, 4 non-serious adverse events and 5 serious adverse events assessed a probable or possible causal relationship to the investigational medical product. Across the NicaPlant® groups there was 1 case of moderate vasospasm, while in the standard of care group there were 2 cases of severe vasospasm.Discussion and conclusionThe placement of NicaPlant® during clip ligation of a ruptured cerebral aneurysm raised no safety concern. The dose of 10 NicaPlant® implants was selected for further clinical studies.

2020-02-01·Journal of Neurosurgery1区 · 医学

In vitro and in vivo testing of a novel local nicardipine delivery system to the brain: a preclinical study

1区 · 医学

Article

作者: Prinz, Vincent ; Bayerl, Simon H. ; Nieminen-Kelhä, Melina ; Adage, Tiziana ; Ghori, Adnan ; Vajkoczy, Peter ; Breitenbach, Jörg

OBJECTIVEThe management of patients with aneurysmal subarachnoid hemorrhage (aSAH) remains a highly demanding challenge in critical care medicine. Despite all efforts, the calcium channel antagonist nimodipine remains the only drug approved for improving outcomes after aSAH. However, in its current form of application, it provides less than optimal efficacy and causes dose-limiting hypotension in a substantial number of patients. Here, the authors tested in vitro the release dynamics of a novel formulation of the calcium channel blocker nicardipine and in vivo local tolerance and tissue reaction using a chronic cranial window model in mice.METHODSTo characterize the release kinetics in vitro, dissolution experiments were performed using artificial cerebrospinal fluid over a time period of 21 days. The excipients used in this formulation (NicaPlant) for sustained nicardipine release are a mixture of two completely degradable polymers. A chronic cranial window in C57BL/6 mice was prepared, and NicaPlant slices were placed in proximity to the exposed cerebral vasculature. Epifluorescence video microscopy was performed right after implantation and on days 3 and 7 after surgery. Vessel diameter of the arteries and veins, vessel permeability, vessel configuration, and leukocyte–endothelial cell interaction were quantified by computer-assisted analysis. Immunofluorescence staining was performed to analyze inflammatory reactions and neuronal alterations.RESULTSIn vitro the nicardipine release profile showed an almost linear curve with about 80% release at day 15 and full release at day 21. In vivo epifluorescence video microscopy showed a significantly higher arterial vessel diameter in the NicaPlant group due to vessel dilatation (21.6 ± 2.6 µm vs 17.8 ± 1.5 µm in controls, p < 0.01) confirming vasoactivity of the implant, whereas the venous diameter was not affected. Vessel dilatation did not have any influence on the vessel permeability measured by contrast extravasation of the fluorescent dye in epifluorescence microscopy. Further, an increased leukocyte–endothelial cell interaction due to the implant could not be detected. Histological analysis did not show any microglial activation or accumulation. No structural neuronal changes were observed.CONCLUSIONSNicaPlant provides continuous in vitro release of nicardipine over a 3-week observation period. In vivo testing confirmed vasoactivity and lack of toxicity. The local application of this novel nicardipine delivery system to the subarachnoid space is a promising tool to improve patient outcomes while avoiding systemic side effects.

100 项与 NicaPlant 相关的药物交易

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