Objective: To evaluate the PK and relative bioavailability of ND0701, a subcutaneously (SC) infused apomorphine-base product candidate, and a commercial apomorphine-HCl product. The secondary objective was to assess these products’ relative safety and tolerability.

Background: Current commercial apomorphine formulations based on apomorphine-HCl require daily SC administration of large volumes and are associated with skin tolerability issues that limit its more widespread adoption. ND0701 is a newly developed concentrated formulation of apomorphine for continuous SC infusion, intended for the treatment of motor fluctuations in patients with Parkinson’s disease which are not sufficiently controlled by oral anti-Parkinson medication. This concentrated formulation allows the reduction of the infused volume and expected to be delivered in a user friendly patch pump.

Methods: This was an open-label, 2-sequence randomized, single center, 3 single dose, 12-hour administration, partial cross-over study in 18 healthy subjects to compare the PK of ND0701 to APO-go®, a commercial apomorphine-HCL product. PK blood samples were collected for determination of apomorphine plasma concentrations. Safety and tolerability assessments were completed up to follow-up visit (28 Days).

Results: The plasma concentrations of apomorphine rose to a plateau typically around 4.5 hours. The bioavailability of apomorphine from ND0701 was comparable to that of commercial apomorphine-HCl as reflected by the ratios of Cmax, AUC(0-last) and AUC(0-inf) which were close to 1.   

The systemic and local safety profile of ND0701 was better than commercial apomorphine-HCl exhibiting lower values of total number of TEAEs (14 vs. 28, respectively) and less prominent nodules formation (small nodules 6 vs. 10, medium nodules 0 vs. 1, severe nodules 0 vs. 1 and 16.7% vs. 30% nodules still present at 28 days’ follow-up, respectively). These results were aligned with the findings from previous pre-clinical studies, showing superior local safety and tolerability, with comparable PK to commercial apomorphine–HCl.

Conclusions: The findings suggest that ND0701 may offer a convenient, easier-to-use and more tolerable alternative to the currently available apomorphine–HCl drug products. Further clinical studies with ND0701 are imminent.

« Back to 2017 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/nd0701-a-new-concentrated-formulation-of-apomorphine-for-continuous-subcutaneous-administration-human-pk-data/