Pramipexole safe and effective in treating restless legs syndrome, study shows

- Therapeutic effects seen within one week of initiating treatment -

RIDGEFIELD, CT, August 24, 2006 – According to a study published in the journal Neurology, pramipexole significantly improved RLS symptoms in patients with moderate-to-severe restless legs syndrome (RLS) versus those on placebo, as measured by both of the study’s primary efficacy endpoints. Furthermore, therapeutic effects were evident within one week of initiating treatment, and pramipexole demonstrated a favorable safety profile.

Significant treatment effects were also apparent for the study’s secondary efficacy endpoints, where pramipexole improved ratings of daytime and nighttime symptom severity, as well as sleep satisfaction and quality of life. Primary efficacy endpoints were measured by patient ratings of symptom severity using the International RLS Study Group Rating Scale (IRLS), and clinician ratings of improvement on the Clinical Global Impressions-Improvement Scale (CGI-I). Secondary endpoints for the study included the Patient Global Impression (PGI) responder rate, visual analogue scale (VAS) ratings of sleep, quality of life as measured by the Johns Hopkins Restless Legs Syndrome Qualify of Life (RLS-QOL) questionnaire, and safety.

“It was gratifying to see that after treatment with pramipexole patients were not only improving from their physician’s perspective, but from their own perspective as well. Secondarily, we found that treatment with pramipexole significantly improved patients’ qualify of life,” said lead investigator, John W. Winkelman, MD, PhD, Medical Director, Sleep Health Center, Brigham and Women’s Hospital. “It was also noteworthy that significant effects were apparent even at the lowest dose investigated.”

About the study
Winkelman et al conducted a 12-week, multicenter, double-blind, randomized, placebo-controlled study of fixed daily doses of pramipexole (0.25 mg, 0.50 mg, and 0.75 mg) involving 344 patients with moderate to severe RLS. Data from 339 patients were analyzed to evaluate the effect of pramipexole treatment on efficacy and safety. The mean age of patients was 51.4 years and the mean duration of RLS symptoms was 5.1 years. All patients were instructed to take pramipexole two-three hours before bedtime.

After 12 weeks, the mean IRLS change in total score from baseline was greater in patients receiving each pramipexole dose (improvement of 12.8 for 0.25mg, 13.8 for 0.50mg, and 14.0 for 0.75mg) than in those patients receiving placebo (improvement of 9.3). In the study, more pramipexole-treatment patients (72 percent) were assessed as CGI-I responders than placebo-treated patients (51.2 percent), and at each pramipexole dose level the comparison with placebo was significant (p < 0.05).

In this study, the overall frequency of adverse events was similar in all treatment groups, and most side effects were judged to be of minor severity. The frequency of adverse events was higher in the pramipexole groups, as a whole, than in the placebo group, and a dose relationship was evident for nausea. The most commonly reported adverse events included nausea (19.0 percent), headache (17.8 percent), insomnia (10.5 percent) and somnolence (10.1 percent).

About restless legs syndrome (RLS)
RLS is a common, yet often undiagnosed, neurological sensorimotor disorder. Nearly ten percent of the U.S. adult population is affected by RLS, and approximately 12 million Americans suffer from moderate to severe symptoms. Patients with RLS often experience an urge to move their legs at night due to uncomfortable leg sensations that worsen during periods of rest or inactivity, often interfere with the ability to sleep, and are partially or totally relieved with movement, such as walking or stretching. While symptoms can vary from person to person, they are generally described as an urge to move the legs accompanied by burning, creeping, crawling, aching, tingling, or tugging sensations in the legs. Additionally, people with RLS will often have disruptions in sleeping, which may be caused by periodic limb movements (PLMs). Approximately one-third of sufferers experience symptoms more than twice weekly causing moderate to severe distress.

As a direct result of RLS, patients may experience daytime tiredness, mood disturbance, and inability to perform daily activities, which can have a substantial negative impact on patients’ quality of life (QOL). Leg discomfort, sleep disturbance, and fatigue can, in turn, impact daily functioning by affecting a patient’s ability to work and participate in social activities and family life. A recent study indicated that more than one third of RLS patients who experienced symptoms at least twice a week reported that their symptoms had a high negative impact on their QOL. In a subanalysis of another study, patients with more severe RLS had lower QOL scores than patients with diabetes, hypertension, other cardiovascular conditions, and osteoarthritis.

Despite many years of research and increased disease recognition, RLS still remains underdiagnosed or misdiagnosed to this day. RLS is actually fairly easy to diagnose with positive answers to the following criteria, which were developed by participants in the RLS Diagnosis & Epidemiology workshop at the National Institutes of Health in collaboration with members of the International Restless Legs Syndrome Study Group (IRLSSG):

Do you have an urge to move your legs, usually accompanied by uncomfortable leg sensations?
Do your symptoms begin or worsen during rest or inactivity, such as lying down or sitting?
Are your RLS symptoms partially or totally relieved by movement, such as walking or stretching?
Are your RLS symptoms worse in the evening or at night, or do they only occur in the evening and at night?

About pramipexole
Pramipexole, a compound from Boehringer Ingelheim research, is approved in the U.S. for the treatment of the signs and symptoms of idiopathic Parkinson's disease. An application has been submitted to the Food and Drug Administration (FDA) for pramipexole for the treatment of moderate to severe primary RLS. Pramipexole is supported by nearly a decade of real-world experience in the treatment of Parkinson’s disease, and approximately 9.1 million prescriptions for pramipexole have been written in the U.S. since its launch in 1997.

Pramipexole may cause patients to fall asleep without any warning, even while doing normal daily activities such as driving.

When taking pramipexole hallucinations may occur and sometimes patients may feel dizzy, sweaty or nauseated upon standing up. The most common side effects in clinical trials for RLS were nausea, headache, and tiredness. The most commonly reported adverse events in early and late Parkinson’s disease in clinical trials were dizziness, involuntary movement, hallucinations, headache, difficulty falling asleep, sleepiness, and nausea. Patients and caregivers should be informed that impulse control disorders/compulsive behaviors may occur while taking medicines, including pramipexole, to treat Parkinson’s disease.

Boehringer Ingelheim Pharmaceuticals, Inc.
Boehringer Ingelheim Pharmaceuticals, Inc., based in Ridgefield, CT, is the largest U.S. subsidiary of Boehringer Ingelheim Corporation (Ridgefield, CT) and a member of the Boehringer Ingelheim group of companies.

The Boehringer Ingelheim group is one of the world’s 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 143 affiliates in 47 countries and approximately 37,500 employees. Since it was founded in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel products of high therapeutic value for human and veterinary medicine.

In 2005, Boehringer Ingelheim posted net sales of US $11.8 billion (9.5 billion euro) while spending approximately one-fifth of net sales in its largest business segment, Prescription Medicines, on research and development.

For more information, please visit http://us.boehringer-ingelheim.com.

Contacts

Kate O'Connor
Public Relations
Boehringer Ingelheim Pharmaceuticals, Inc.
900 Ridgebury Road
Ridgefield, CT 06877
Phone: (203) 791-6250
koconno4@rdg.boehringer-ingelheim.com

References

Winkelman J, Sethi K, Kushida C, Becker P, Koester J, Cappola J, Reess J. Efficacy and safety of pramipexole in restless legs syndrome. Neurology. Published August 23, 2006.