Coastal Neurological
Medical Group, Inc.

Ropinirole 24 hour Prolonged Release (Requip XL) Clinical Trial Results
By Dee E. Silver, M.D.

Ropinirole 24 hour prolonged release (Requip XL) oral dose was studied as an adjunct (add on) to therapy in patients with Parkinson's disease who were on levodopa and had motor fluctuations ("off" time). In a double-blind, placebo-controlled study, almost 400 patients were randomized to either Requip XL or placebo. There were a number of outcome measures, but the primary outcome measure was the reduction in the hours of "off" time in a day at 24 weeks. The mean dose of Requip XL was 18.8 mg per day. The primary end point was met and there was a mean reduction in daily "off" time by 2.1 hours in the Requip XL group and 0.3 hours in the placebo group. This was statistically significant to a p Value of <0.0001. The average reduction in the daily levodopa dose for those patients on Requip XL was 278 mg. There were significant secondary outcome measures that were statistically improved over placebo. They were the percent of daily "on" time and the "on" time without troublesome dyskinesias. The UPDRS motor scores were statistically better for Requip XL as compared to placebo, as were activities of daily living subscales, a depression inventory, and some subscales for mobility, emotional well-being, and communication. There was also a statistically significant improvement in sleep when measured by the PD sleep scale. This clinical trial hence documents the benefit of Requip XL over placebo.

Adverse events or side effects for Requip XL were dyskinesias, nausea, dizziness, sleepiness, hallucinations, and orthostatic hypotension. Most of the side effects were seen in the first 4 weeks of the titration phase, before the levodopa dose could be reduced. Only 5% of the patients in the study withdrew from both the Requip XL group and the placebo group. Most side effects were well tolerated and did not result in a higher discontinuance rate for Requip XL as compared to placebo. Even though more patients on Requip XL had more dyskinesias, the amount of time spent in the "on" state without troublesome dyskinesias was similar in each treatment group. At the end of the study there wasn't a significant amount of increased "on" time with troublesome dyskinesias for the Requip XL group. Hallucinations were more common in the Requip XL group than the placebo group. 8% of the patients in the Requip XL group had hallucinations and only 2% in the placebo group. Reduction in the total levodopa dose seemed to handle most of the adverse side effects. There was one unintended sleep episode and one episode of syncope that occurred in patients with Requip XL.

Requip XL seems to have a very comparable reduction in "off" time when comparing to other dopamine agonists that have been studied in other clinical trials in the past. Knowing that it is clinically difficult to compare clinical trials, this comparison can sometimes give an idea of relationships to effectiveness of a drug. Pergolide, which is no longer available, when studied and compared to placebo, had a reduction in "off" time of about 1.6 hours. Pramipexole gave a reduction in "off" time in the clinical trials of 2.0 hours. In a trial comparing rasagiline 1 mg and entacapone 200 mg with each levodopa dose there was a reduction in "off´ time of about one hour for each drug. In another trial, Rasagiline at 1 mg per day has been shown to reduce "off" time by about one hour.

When looking back at the immediate release ropinirole (Requip IR) clinical trials, it can be seen that the Requip XL drug has a higher percentage of patients who have greater than 20% reduction in the levodopa dose and greater than 20% reduction in the daily "off" time. This percentage was 35% for the Requip IR and 52% for the Requip XL. Also, there has been a reduction in the adverse events when comparing the Requip XL trial and comparing the data from adverse events in the Requip IR trials.

There may be new data on follow-up of these patients for a longer period of time. This study documents evidence-based medicine and effectiveness of a drug when compared to placebo in patients who are not optimized by management with levodopa, i.e. had "off" time and dyskinesias.

Requip XL will be most likely be available by the time this article is printed. Pramipexole (Mirapex), MAO-B inhibitors (rasagiline or selegiline), or generic Requip (ropinirole) may be tried first, and/or dose and frequency changes may be made before using Requip XL to improve the patient's symptoms.

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Coastal Neurological Medical Group
9850 Genesee Avenue
Suite 860
La Jolla, CA 92037
Tel: 858.453.3842
Fax: 858.535.9390

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