Objective:

An analysis of the proportion of patients who turned ON after CVT-301 84mg treatment vs placebo, compared across patient subgroups with different baseline UPDRS-III scores when experiencing an OFF period in the Phase 3 SPAN-PD study.

Background:

SPAN-PD was an efficacy and safety study of CVT-301 in patients on a stable levodopa/dopa-decarboxylase inhibitor regimen experiencing ≥2h daily OFF periods. Patients were randomized to placebo/CVT-301 for OFF symptom treatment as needed ≤5 times/day. CVT-301 84mg significantly improved motor function at week 12, 30 min post-dose, as measured by lower UPDRS-III scores, with improvement recorded as early as 10 min post-dose. Proportion of patients achieving an ON state at week 12 also demonstrated significant superiority of CVT-301 over placebo (58% of CVT-301 84mg patients turned ON and remained ON at 60 min post-dose, vs 36% of placebo).

Design/Methods:

Analysis compared patients stratified by examiner-rated OFF UPDRS-III score at screening (median UPDRS-III score ≤33 “low” (range 8-33) vs >33 “high” (range 34-75). Treatment differences were calculated between CVT-301 84mg and placebo for the proportion of patients who turned ON and remained ON at 60 min post-dose at week 12 (stratified by Hoehn & Yahr stage, and screening spirometry).

Results:

In the low UPDRS-III group (≤33, n=104) at week 12, 30 (50.0%) CVT-301 patients turned ON post-dose and remained ON at 60 min compared with 11 (25.0%) placebo patients (odds ratio [OR] 3.0, P=0.011). In the high UPDRS group (>33, n=90) at week 12, 26 (70.3%) CVT-301 patients turned ON post-dose vs 24 (45.3%) on placebo (OR 2.8, P=0.026).

Conclusions:

In SPAN-PD, CVT-301 84mg was significantly more effective than placebo in turning patients ON at week 12 in both subpopulations of PD patients experiencing, respectively, more or less severe OFF periods at screening. No substantive difference in drug response was observed between the more and less severe groups.