ND0701, A Novel Formulation of Apomorphine for Subcutaneous Infusion, in Comparison to a Commercial Apomorphine Formulation: 28-Day Pharmacokinetic Study in Minipigs and a Phase I Study in Healthy Volunteers to Assess the Safety, Tolerability, Pharmacokinetics and Relative Bioavailability.

Background: Subcutaneous apomorphine is used for the treatment of Parkinson's disease (PD); however, infusion site reactions are a common adverse event (AE), which can lead to treatment discontinuation. Apomorphine formulations that are more tolerable and convenient for use are needed.

Objective: Our aim was to compare the toxicity and bioavailability of ND0701, a new concentrated formulation of apomorphine free base, with one of the commercially available apomorphine HCl formulations (APO-go, Britannia Pharmaceuticals Ltd).

Methods: (1) Preclinical study: 16 minipigs were randomly assigned to placebo, APO-go, and ND0701 groups, and treated for 28 days. Pharmacokinetic, clinical, and pathological assessments were performed. (2) Phase I study: 18 healthy volunteers participated in an open-label, two-sequence, randomized, three single-dose, partial crossover study to compare the pharmacokinetics, safety, and tolerability of ND0701 with APO-go (1%).

Results: (1) Preclinical study: No systemic toxicity was observed in apomorphine-treated minipigs, but local skin reactions were observed at the infusion sites. These effects were less frequent and less severe and recovery was more rapid for ND0701 compared with APO-go. (2) Phase I study: Both formulations were safe and well tolerated under the conditions of the study and no severe or serious treatment-emergent AEs were reported. Infusion site nodules were reported more frequently, with higher severity, and recovered slower at APO-go-treated sites compared with ND0701-treated sites. Bioavailability of apomorphine was comparable between the two formulations.

Conclusion: Based on these pilot studies, ND0701 appears to be superior to APO-go in terms of tolerability and safety, while maintaining comparable bioavailability with APO-go, and shows promise as a future treatment for PD.