Objective: To characterize the local safety and PK of a novel apomorphine formulation, ND0701, in comparison to a commercially available apomorphine–HCl solution.

Background: Apomorphine is the most potent dopamine agonist that provides anti-Parkinson’s effect comparable to levodopa, and potentially improves dyskinesia. Nevertheless, its long-term use is limited by poor compliance and local site skin reactions, resulting in the formation of nodules that can cause discomfort and may impact the effectiveness of the drug.

Methods: The experiments were conducted in domestic pigs. For the evaluation of local site reactions, four drug formulations, 1% ND0701, 2.5% ND0701, 0.5% apomorphine-HCl or 1% apomorphine-HCl, were administered by subcutaneous continuous infusion of 50 mg apomorphine during 24h, at a volume of 5, 2, 10 and 5 ml, respectively. For the determination of steady state plasma concentration of apomorphine, the drug formulations were administered by subcutaneous continuous infusion of 14 mg apomorphine during 7h, at a rate of 0.2, 0.08, 0.4 and 0.2 ml/h, respectively. Local safety was evaluated using ex-vivo & in-vivo MRI and histopathology.

Results: MRI analysis showed that local site reactions following continuous subcutaneous administration of ND0701, at concentrations as high as ×2.5-5 than those of Apomorphine-HCl, were significantly smaller and exhibited better recovery. Histopathological evaluation supported these findings showing only a minimal, chronic inflammatory reaction following continuous subcutaneous administration of 1% and 2.5% ND0701, while mild, chronic, granulomatous inflammation and necrosis of the subcutis were observed following Apomorphine-HCl administration. Steady state plasma concentrations of apomorphine were attained after ∼2.5 hours and were similar (5.4 ±1.8 ng/ml) among all 4 tested formulations, demonstrating that 1% and 2.5% ND0701 formulations are bioequivalent to the commercially available Apomorphine-HCl formulation.

Conclusions: ND0701, at 1% and 2.5%, exhibited superior local safety and tolerability, with equivalent PK, as compared to 0.5% and 1% apomorphine–HCl, thereby presenting an improved alternative to the existing apomorphine formulations, that will allow, for the first time, the use of a descrete, ‘one-and-done’, easy to use patch pump in advanced PD.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/nd0701-a-novel-safe-concentrated-apomorphine-formulation-for-continuous-subcutaneous-administration-via-a-patch-pump/