Combined single inhaled doses of CVT-301 (inhaled levodopa) and oral carbidopa/levodopa therapy taken during early morning OFF symptoms demonstrated tolerability and lack of serious adverse events according to research published in Parkinsonism & Related Disorders.
This randomized, double-blinded, 2-way crossover study included 36 individuals (mean age, 62.9 years) with Parkinson disease who self-administered either CVT-301 (84 mg) or placebo during an early morning OFF phase, just after their oral dose of carbidopa/levodopa and at least 8 hours from the previous night’s dose of carbidopa/levodopa. Treatment-emergent adverse events, dyskinesia, and vital signs comprised safety assessments, with an additional assessment of examiner-rated time-to-ON phase for treatment vs placebo. Descriptive statistics were used to present data on safety and tolerability, while the Wilcoxon-Gehan rank-sum test for crossover data was used to compare treatment and placebo.
Treatment-emergent adverse events occurred in 25% (n=9) of study participants after administration of CVT-301 and in 11.1% (n=4) after administration of placebo. No deaths, serious adverse events, or adverse events leading to study discontinuation were reported. Mild cough was the most common adverse event among those in the treatment and placebo groups 11.1% (n=4) vs 2.8% (n=1), respectively. Comparable incidences of asymptomatic orthostatic hypotension (n=6 vs n=7) and examiner-rated dyskinesia (mild, n=13 vs n=14; moderate, n=2 vs n=1; severe, n=0 vs n=0) was reported between treatment and placebo groups, respectively. Median time to ON time for CVT-301 treatment vs placebo was 25.0 minutes vs 35.5 minutes, respectively, though the difference was not statistically significant (P =.26). At the 30-minute mark, treatment group was found to have a higher rate of ON (66.7%; n=24) when compared with the placebo group (44.5%; n=16; P =.040).
Investigators indicate limitations to this study include the lack of power to assess the exploratory efficacy of end points and insufficient sensitivity to detect changes over a short time period.
The researchers conclude that “single inhaled doses of CVT-301 84 mg taken during an early morning OFF period together with routine oral [carbidopa/levodopa] therapy were well-tolerated by patients with [Parkinson disease] and produced no serious [treatment-emergent adverse events].”
This study was funded by Acorda Therapeutics, Inc. Several authors report financial associations with pharmaceutical companies and with the funding source. For a full list of author disclosures, see the reference.
Hauser RA, Isaacson SH, Ellenbogen A, et al. Orally inhaled levodopa (CVT-301) for early morning OFF periods in Parkinson’s disease [published online March 30, 2019]. Parkinsonism Relat Disord. doi: 10.1016/j.parkreldis.2019.03.026