Objective: A post hoc analysis of UPDRS-III sequential changes over the 12-week treatment period of a phase 3 study.

Background: CVT-301 is an inhaled levodopa (LD) for OFF period treatment in people with Parkinson’s disease (PD) on an oral dopa-decarboxylase-inhibitor/LD regimen. In the SPAN-PD study[1], CVT-301 84 mg improved motor function in patients with OFF periods at week 12, as measured by lower UPDRS-III scores, 30 min postdose (P=0.009 vs placebo); 58% of subjects achieved and maintained an ON state within 60 min postdose vs 36% on placebo (P=0.003).

Method: PD subjects (n=351) experiencing OFF periods and on a stable oral carbidopa/LD regimen were randomized to placebo or CVT-301 60 mg or 84 mg for treatment of OFF period symptoms up to 5 times/day. UPDRS-III was assessed during screening and at predose,10, 20, 30, and 60 min postdose at weeks 4, 8, and 12 treatment visits.

Results: CVT-301 84 mg was associated with consistent improvement in mean UPDRS-III scores at all timepoints postdose, and at all visits (every 4 weeks) when administered in an OFF period. Mean placebo scores improved in the first 20 min postdose at all visits, but at >20 min remained largely unchanged, whereas CVT-301 scores continued to improve through 60 min. Mean UPDRS-III score % improvement from predose showed that CVT-301 84 mg improved within 60 min postdose at each visit, whereas placebo % improved until 20 min and then largely declined. When in an OFF period, subjects achieved a clinically relevant improvement of 30% by 20 min at 4 weeks and by 30 min at all other visits for CVT-301, whereas the placebo group did not achieve this threshold at any visit. Mean UPDRS-III score for fully ON CVT-301 subjects at screening (after subject’s usual oral carbidopa/LD dose) was 14.9. At 30 min postdose mean UPDRS-III score for CVT-301 subjects at each visit returned to an ON range of 18.3-19.3.

Conclusion: CVT-301 84 mg was associated with consistent improvements in UPDRS-III scores at weeks 4 through 12 when administered in an OFF period and improvements were consistently greater than placebo. CVT-301 produced clinically significant UPDRS-III (≥30%) improvement as soon as 20-30 min postdose and improvements were sustained through 60 min. This data demonstrates that CVT-301 consistently improves UPDRS-III with a rapid onset and durable effect over time for up to 12 weeks.

References: 1. LeWitt PA, Hauser RA, Pahwa R, et al. Safety and efficacy of CVT-301 (levodopa inhalation powder) on motor function during off periods in subjects with Parkinson’s disease: a randomised, double-blind, placebo-controlled phase 3 trial. Lancet Neurol. 2019;18(2):145-154.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/cvt-301-treatment-provides-consistent-and-clinically-significant-improvements-in-unified-parkinsons-disease-rating-scale-part-iii-updrs-iii-over-12-weeks/