SAN DIEGO—Inhaled levodopa rapidly improves motor function when patients with Parkinson’s disease use the therapy at the onset of off states, according to research presented at the 19th International Congress of Parkinson’s Disease and Movement Disorders. In addition, the therapy, CVT-301, does not increase on time with dyskinesia.
CVT-301 was developed to treat off episodes that can result from irregular absorption of oral levodopa. To test the safety and efficacy of the therapy, Peter LeWitt, MD, Director of the Parkinson’s Disease and Movement Disorders Program at Henry Ford Hospital in West Bloomfield, Michigan, and Professor of Neurology at Wayne State University School of Medicine in Detroit, and his research colleagues randomized 86 patients to CVT-301 or placebo in a double-blind study. Participants had at least two hours of off time each day (mean, 5.9 hours), not including morning off time.
Peter LeWitt, MD
Over four weeks, participants used CVT-301 or placebo as an adjunct to usual Parkinson’s disease medications, including oral levodopa. Patients self-administered CVT-301 or placebo as soon as possible after the emergence of off symptoms as many as three times daily. Two levodopa fine-particle doses were studied: 35 mg during the first two weeks of the study and 50 mg during the second two weeks. Serial United Parkinson’s Disease Rating Scale (UPDRS) III evaluations were performed at in-clinic visits during weeks 1, 2, and 4. Scores were recorded in a predose off state and at 10, 20, 30, and 60 minutes post dose. In addition, Parkinson’s disease diary entries were used to evaluate daily off time and on time with and without dyskinesia. The average frequency of at-home use of CVT-301 and placebo was 2.1 times per day. Medication preparation took about 30 seconds, and patients reported no difficulties using the drug-inhaler system.
By least-squares mean change, CVT-301 showed significant improvement of motor function on UPDRS III. For 35 mg of CVT-301, the change was –9.9, compared with –5.3 for placebo. For 50 mg, the change was –10.0, compared with –3.1 for placebo. Motor function improved as early as 10 minutes after inhalation of the study drug, Dr. LeWitt said. Diary entries showed that CVT-301 at 50 mg reduced off time by 1.6 hours per day, which was a significant improvement, compared with placebo.
Twenty patients (47%) in the CVT-301 group and 14 patients (33%) in the placebo group reported one or more treatment-emergent adverse events, including dizziness, cough, and nausea. No severe treatment-emergent adverse events were reported in the CVT-301 group. One patient in the placebo group had dyskinesia that was recorded as a severe adverse event. No cardiovascular or pulmonary function adverse events were reported. Pulmonary function tests throughout the study showed that values were within normal ranges for both groups.
“This work is important, as it appears to offer a further and novel route of administration of levodopa that can be used to treat off periods,” said Peter Jenner, PhD, DSc, Professor of Pharmacology and Therapeutics at King’s College London. “It will offer an alternative to rescue from off periods currently achieved by subcutaneous injection of apomorphine. A noninvasive form of rescue therapy will have utility and convenience for patients with Parkinson’s disease experiencing sudden off [time] and improve their quality of life.”