A new low-dose formulation of selegiline: clinical efficacy, patient preference and selectivity for MAO-B inhibition

Abstract

Three studies were performed using a fast dissolving formulation of selegiline hydrochloride designed for buccal absorption "Zydis Selegiline". The aim of the first study was to compare the therapeutic efficacy of Zydis Selegiline (1.25 mg or 10 mg) with conventional selegiline hydrochloride tablets "conventional selegiline tablets" (10 mg) in patients with Parkinson's disease (PD) who were previously treated with conventional selegiline tablets as an adjunct to levodopa/dopamine agonist therapy. Patients were observed for 4 weeks to ensure that they were stable. Stable patients (n=197) were then randomised to continue with conventional selegiline tablets 10 mg (n=68), or to treatment with Zydis Selegiline 1.25 mg (n=64) or Zydis Selegiline 10 mg (n=62) for 12 weeks in this randomised, parallel group study. A further aim was to establish the acceptability of Zydis Selegiline compared with conventional selegiline tablets. Patient preference for Zydis Selegiline was also evaluated in a second study, a single-dose, randomised, two-way crossover study conducted in patients with PD (n=148). Patients were stratified by the presence or absence of swallowing and salivation problems and were randomised to either Zydis Selegiline 5 mg or a placebo fast-dissolving formulation. In a third study, the degree of potentiation of the tyramine pressor effect following Zydis Selegiline was compared with that following conventional selegiline tablets in healthy volunteers. A total of 24 healthy volunteers were randomised to receive Zydis Selegiline 1.25 mg or conventional selegiline tablets 10 mg for 14-16 days in an open-label, randomised parallel group study. Both Zydis Selegiline (1.25 mg and 10 mg) treatments were shown to be therapeutically equivalent to conventional selegiline tablets 10 mg based on comparison of mean total Unified Parkinson's Disease Rating Scale (UPDRS) scores. Therapeutic equivalence was defined a priori as the 90% confidence interval (CI) for the difference in total UPDRS scores between groups to lie entirely within the range +/-5. The difference (90% CI) in mean adjusted total UPDRS between Zydis Selegiline 1.25 mg and conventional selegiline tablets 10 mg was -2.50 (-4.84, -0.17), and for Zydis Selegiline 10 mg and conventional selegiline tablets 10 mg, 0.04 (-2.30, 2.38). For the motor subscores of the UPDRS, differences between adjusted means (90% CI) compared with the conventional selegiline tablets group were: Zydis Selegiline 1.25 mg, -2.14 (-3.94, -0.33) and Zydis Selegiline 10 mg, -0.90 (-2.70, +0.91). Patients who switched from conventional selegiline tablets to Zydis Selegiline 1.25 mg showed a slight improvement in UPDRS scores following 12 weeks of treatment (standard error of difference 1.039; p=0.01). In the single-dose crossover study, most (61%) patients liked Zydis Selegiline 5 mg; a significantly greater proportion than the null hypothesis of 50% (p<0.002). However, only 62 patients (46%) indicated that they liked the taste of Zydis Selegiline. Nevertheless, the proportion of patients wh...

Tablets and Other Solid Dosage Forms for Systemic Oral Mucosal Drug Delivery

“…An open-label, randomized study compared the therapeutic effects of conventional selegiline 10-mg tablets with Zydis selegiline 1.25 mg and Zydis selegiline 10-mg tablets in patients with PD who previously were receiving treatment with conventional selegiline tablets 10 mg daily as an adjunct treatment to levodopa or a dopamine agonist [48]. It was found that Zydis selegiline 1.25 and 10 mg were therapeutically equivalent to the conventional selegiline oral tablets.…”

A Comparative Study Between Spray-Drying and Fluidized Bed Coating Processes for the Preparation of Pramipexole Controlled-Release Microparticles for Orally Disintegrating Tablets

“…Considering symptoms of Parkinson's disease (e.g., tremors and dysphagia), controlledrelease ODTs could improve patient compliance due to easy administration and reduced dose frequency. [28,29] The aims of present study were to prepare controlledrelease microparticles containing PRM for ODTs using two different processes, spray drying and fluidized bed coating, and to characterize their physicochemical properties including in vitro release rate and morphology.…”

Zydis selegiline in the management of Parkinson's disease

“…The first was an open-label, randomized study comparing the therapeutic effects of conventional selegiline 10 mg tablet, Zydis selegiline 1.25 mg and Zydis selegiline 10 mg in patients with PD who, prior to the study, were receiving treatment with conventional selegiline tablets 10 mg daily as an adjunct treatment to levodopa or a dopamine agonist [45] . Patients had to be ≥ 18 years of age and have a Hoehn and Yahr stage 2 or greater during ' off ' or untreated periods and were excluded if they had unstable symptoms of PD or significant concurrent conditions and therapies that could interfere with selegiline action.…”

“…Thus, despite increasing MAO-B inhibitory activity with larger doses of Zydis selegiline, MAO-A inhibitory activity did not appear to be enhanced. The specific tyramine pressor response was evaluated in an open-label, randomized, parallel group comparison in healthy volunteers before and after 2 weeks of treatment with Zydis selegiline 1.25 mg or oral selegiline 10 mg tablet [45] . Starting at 100 mg, escalating doses of oral tyramine were used to determine the dose in which 50% of the subjects had a 30 mmHg rise from baseline systolic blood pressure (PD 50 ).…”