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

Background: SPAN-PD[1] was a double-blind, placebo-controlled 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 treatment of OFF symptoms as needed ≤5 times/day. SPAN-PD showed that CVT-301 84mg improved motor function at week 12, 30 min post-dose, as measured by lower UPDRS-III scores (LS difference -3.92 CVT-301 vs placebo, P=0.009). Improvement was recorded as early as 10 min post-dose. Proportion of patients achieving an ON state at week 12 also demonstrated superiority of CVT-301 over placebo with 58% of CVT-301 84mg patients who turned ON and remained ON at 60min post-dose vs 36% of placebo patients (odds ratio [OR] 2.65, 95% confidence intervals [CI] 1.48-4.76, P=0.0027).

Method: This 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 analyzed 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. ORs and 95%CIs for CVT-301 vs placebo were calculated based on Cochran-Mantel-Haenszel tests by the stratification factors, 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 had turned ON post-dose and remained ON at 60 min compared with 11 (25.0%) placebo patients (CVT-301 vs placebo OR 3.0, 95%CI 1.3-6.9, P=0.011). In the high UPDRS group (>33, n=90) at week 12, 26 (70.3%) CVT-301 patients had turned ON post-dose vs 24 (45.3%) on placebo (OR 2.8, 95%CI 1.1-6.7, P=0.026).

Conclusion: 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, and no substantive difference in drug response was observed between the more and less severe groups.

References: [1] LeWitt PA, Hauser RA, Pahwa R, et al. Lancet Neurol. 2019;18(2):145-154.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/subgroup-analyses-by-unified-parkinsons-disease-rating-scale-part-iii-updrs-iii-of-patients-treated-with-levodopa-inhalation-powder-84mg-or-placebo-to-treat-off-symptoms-in-patients-with-pa/