Pulmonary Safety and Tolerability of Inhaled Levodopa (CVT-301) Administered to Patients with Parkinson's Disease.

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.

Pregabalin for the treatment of fibromyalgia syndrome: results of a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: Fibromyalgia syndrome (FMS) is characterized by widespread musculoskeletal pain and lowered pain threshold. Other prominent symptoms include disordered sleep and fatigue. FMS affects an estimated 2% of the population, predominantly women. This trial was designed to evaluate the efficacy and safety of pregabalin, a novel alpha(2)-delta ligand, for treatment of symptoms associated with FMS. METHODS: This multicenter, double-blind, 8-week, randomized clinical trial compared the effects of placebo with those of 150, 300, and 450 mg/day pregabalin on pain, sleep, fatigue, and health-related quality of life in 529 patients with FMS. The primary outcome variable was the comparison of end point mean pain scores, derived from daily diary ratings of pain intensity, between each of the pregabalin treatment groups and the placebo group. RESULTS: Pregabalin at 450 mg/day significantly reduced the average severity of pain in the primary analysis compared with placebo (-0.93 on a 0-10 scale) (P /=50% improvement in pain at the end point (29%, versus 13% in the placebo group; P = 0.003). Pregabalin at 300 and 450 mg/day was associated with significant improvements in sleep quality, fatigue, and global measures of change. Pregabalin at 450 mg/day improved several domains of health-related quality of life. Dizziness and somnolence were the most frequent adverse events. Rates of discontinuation due to adverse events were similar across all 4 treatment groups. CONCLUSION: Pregabalin at 450 mg/day was efficacious for the treatment of FMS, reducing symptoms of pain, disturbed sleep, and fatigue compared with placebo. Pregabalin was well tolerated and improved global measures and health-related quality of life.