Pulmonary Safety and Tolerability of Inhaled Levodopa (CVT-301) Administered to Patients with Parkinson's Disease.
LeWitt PA, Pahwa R, Sedkov A, Corbin A, Batycky R, and Murck H. Pulmonary safety and tolerability of inhaled levodopa (cvt-301) administered to patients with Parkinson's disease. J Aerosol Med Pulm Drug Deliv 2018; 31(3):155-161.
J Aerosol Med Pulm Drug Deliv
BACKGROUND: CVT-301, an inhaled levodopa (LD) formulation, is under development for relief of OFF periods in Parkinson's disease (PD). Previously, we reported that CVT-301 improved OFF symptoms relative to placebo. In this study, we evaluate pulmonary function in patients treated with a single dose of CVT-301 or placebo for 3 hours, or received multiple doses/day for 4 weeks.
METHODS: As part of two phase 2 studies, pulmonary safety and tolerability of CVT-301 were evaluated in PD patients experiencing motor fluctuations (≥2 hours OFF/day), Hoehn and Yahr stage 1-3, and forced expiratory volume in 1 second/forced vital capacity ratio ≥75% of predicted (in ON state). In study A, patients received single doses of oral carbidopa/LD and each of the following via the inhaled route: placebo and 25 and 50 mg LD fine particle dose (FPD) CVT-301. In study B, patients received up to 3 inhaled doses/day of 35 mg (weeks 1-2) and 50 mg LD FPD CVT-301 (weeks 3-4) versus placebo. Assessments included spirometry and treatment-emergent adverse events (TEAEs).
RESULTS: In study A, (n = 24) mean age ± standard deviation was 61.3 ± 7.4 years, mean time since diagnosis was 10.5 ± 4.6 years, and mean duration of LD treatment 8.4 ± 3.7 years. Assessment of pulmonary function (predose to 3 hours postdose) showed that spirometry findings were within normal ranges, regardless of treatment groups, or motor status at screening. In study B, (n = 86) mean age was 62.4 ± 8.7 years, time since PD diagnosis was 9.4 ± 3.9 years, and duration of LD treatment 7.8 ± 3.9 years. Longitudinal assessment of pulmonary function over 4 weeks showed no significant difference in spirometry between CVT-301 versus placebo groups. In both studies, the most common CVT-301 TEAE was mild-to-moderate cough (study A: 21%; study B: 7% vs. 2% in placebo). Other common TEAEs in study B were dizziness and nausea.
CONCLUSION: Acute and longitudinal assessment of pulmonary function showed that CVT-301 treatment was not associated with acute airflow obstruction in this population. CVT-301 was generally safe and well tolerated.
Medical Subject Headings
Administration, Inhalation; Adult; Aged; Aged, 80 and over; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Levodopa; Lung; Male; Middle Aged; Parkinson Disease; Vital Capacity