WASHINGTON — An orally disintegrating formulation of selegiline appears to be a safe and effective adjunct for patients with Parkinson's disease who are experiencing a deterioration of levodopa response, according to data presented in a poster at the World Parkinson Congress.
Selegiline taken in the orally disintegrating form significantly decreased the amount of levodopa nonresponse time, compared with placebo in two phase III, randomized, double-blind trials, reported Dr. William G. Ondo, of the department of neurology at Baylor College of Medicine, Houston.
A selective MAO type-B inhibitor, selegiline is limited by low bioavailability, extensive first-pass hepatic metabolism, and production of amphetamine metabolites. Orally disintegrating tablets dissolve on first contact with saliva and undergo pregastric absorption, minimizing first-pass metabolism and yielding high plasma levels.
Prior to development of an orally disintegrating form of the drug, selegiline—approved for use as an adjunct in treating patients with Parkinson's disease who experience a deterioration in response to levodopa/carbidopa—had been given as a capsule or tablet to be swallowed.
He analyzed data from two trials of orally disintegrating selegiline versus placebo in patients with erosion of efficacy with optimized levodopa therapy. Patients were older than 30 years, had a confirmed diagnosis of Parkinson's disease, had a documented response to levodopa with a dopa-decarboxylase inhibitor, and had at least 3 hours daily when the beneficial effects of levodopa wore off.
Initially, patients in both trials were randomized to placebo or 1.25 mg of orally disintegrating selegiline per day. At week 6, the selegiline dosage was increased to 2.5 mg per day. The mean baseline number of “off” hours was determined using patient recordings for a 24-hour period for 2 days preceding the initial clinic visit. The mean number of “off” hours throughout the trial were also determined using the diaries for the 2 days prior to clinic visits. Six visits were conducted during the 12-week trial.
In the first trial, 98 patients were randomized to selegiline and 50 to placebo; in the second, 94 patients were randomized to selegiline and 48 to placebo.
Combined results from both trials showed that orally disintegrating selegiline significantly decreased total levodopa “off” time at weeks 4–6. The treatment group had 5 hours per day during which efficacy wore off, compared with 6 hours per day for the placebo group (10% vs. 6% reductions from baseline, respectively).
Orally disintegrating selegiline also significantly decreased the percentage of levodopa “off” time at weeks 10–12. The treatment group had 4.5 hours per day during which efficacy wore off, vs. 6 hours per day for the placebo group (about 13% vs. 7% reductions from baseline, respectively).
Orally disintegrating selegiline was generally well tolerated in both trials.