New Data Shows Requip-Modutab Improves Nocturnal Symptoms In Patients With Advanced Parkinson's Disease

Main Category: Parkinson's Disease
Article Date: 12 Jun 2009 - 2:00 PDT

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New data presented at the 13th International Congress of Parkinson's Disease and Movement Disorders show that Requip-Modutab* (ropinirole prolonged release tablets) improves nocturnal symptoms experienced by patients with advanced Parkinson's disease (PD).[i] The data showed that patients with more significant nocturnal symptoms had a greater improvement with Requip-Modutab, when used as an adjunct to levodopa (L-dopa), versus placebo. These data indicate that once-daily Requip-Modutab remains effective in treating PD symptoms over the night as well as during the day and provides benefit to those in most need. Sleep disturbances, a key element of nocturnal symptoms, are one of the most common non-motor complications of PD and can affect up to 98% of patients.[ii]

Professor K Ray Chaudhuri**, Consultant Neurologist and Professor in Neurology / Movement Disorders at Kings College NHS Foundation Trust, and Kings Health Partners, London, UK, commented: "We know already from previous trials that Requip-Modutab is effective in improving symptom control during the day and these latest data now show that it also improves troublesome nocturnal symptoms, offering an effective treatment to patients with moderate to advanced PD during both the day and night. If a patient fails to get a good night's sleep they feel tired and fatigued in the morning which can in turn result in daytime somnolence which has an adverse effect on quality of life. It is therefore critical that we identify and manage nocturnal symptoms to improve the lives not only of patients but also of their carers, who often have to support them during difficult nights."

Nocturnal symptoms - a common problem in PD

A recent pan-European survey revealed that two out of three patients do not feel in control of their symptoms over a 24-hour period, with over 70% waking at least once during the night and nearly one in four rating the quality of their sleep as poor or very poor. As a result, they often struggle to function properly in the morning and throughout the day.[iii] Nocturnal symptoms, which typically increase as the disease progresses, include difficulty staying asleep, hallucinations, urinary incontinence, painful muscle cramps, painful posturing of arms or legs on waking and feeling tired and sleepy after waking.[iv] Treatment strategies that provide continuous dopaminergic stimulation have been shown to improve nocturnal symptoms.[v]

Continuous delivery of Ropinirole

Requip-Modutab has a smooth pharmacokinetic profile that provides continuous delivery of ropinirole over 24 hours. Requip-Modutab's once daily dosing and simple dose titration was developed to reduce the fluctuations associated with three times daily drug regimens.[vi]

Additional study data presented at the congress showed that adjunctive Requip-Modutab, in patients with advanced PD not optimally controlled with L-dopa, achieved a significant reduction in the time when their symptoms were not being controlled during the day ('off' time), compared with placebo. These improvements were seen as early as two weeks following treatment.[vii] By week 24 over 50% of patients receiving adjunctive Requip-Modutab had achieved a maintained reduction in 'off' time. Furthermore, data showed that a greater proportion of Requip-Modutab-treated patients experienced at least a 40% reduction in awake time spent 'off' versus those receiving ropinirole 3x-daily.[viii] These results confirm the benefits of Requip-Modutab in maintaining control of symptoms in advanced PD. Recent safety and tolerability data also confirm that long-term therapy with Requip-Modutab is well tolerated by patients with early or advanced PD.[ix]

** Professor Chaudhuri is an advisor to GSK and has received payment for consultancy, research and speaker engagements relating to Requip Modutab.

About the data

The EASE-PD Adjunct Phase III, double-blind, parallel-group, 24-week study assessed the efficacy and safety of adjunctive Requip-Modutab compared with placebo. A post-hoc analysis of EASE-PD assessed nocturnal symptoms by mean change from baseline in PDSS total score. In patients with a PDSS total score ≤100 at baseline (i.e., those having significant nocturnal symptoms) mean [SD] change from baseline was greater for Requip-Modutab than placebo at both Week 12 and Week 24. Summary results (Requip-Modutab versus placebo in each case): (14.2 [22.80] versus 2.8 [17.60]) at Week 12 OC (Observed Case); (11.3 [25.58] versus 4.0 [20.62]) at Week 24 OC; (10.3 [24.44] versus 2.5 [20.96]) at Week 24 LOCF (Last Observation Carried Forward). No advantage for Requip-Modutab over placebo was observed in the other subgroup of patients with only mild or minimal baseline nocturnal symptoms (PDSS score >100).I

Nocturnal symptoms were measured using the Parkinson's Disease Sleep Scale (PDSS), a validated tool to measure sleep disturbance in PD, which measures 15 commonly reported night-time symptoms: overall quality of sleep (item 1), sleep onset and maintenance (items 2-3), nocturnal restlessness (items 4-5), nocturnal psychosis (items 6-7), nocturia (items 8-9), nocturnal motor symptoms (items 10-13), sleep refreshment (item 14) and daytime dozing (item 15).4 PDSS scores range from 0 (severe sleep disturbance) to 150 (free from symptoms). Patients with a PDSS score ≤100 at baseline are regarded as suffering with significant nocturnal symptoms.

Long-term therapy with Requip-Modutab is well tolerated by patients with early or advanced PD. Treatment-emergent adverse events (TEAEs) are as expected for non-ergot dopamine agonists. Data from two ongoing long-term studies showed that peripheral oedema was the most commonly reported TEAE (55/502 [11%]). The only TEAE leading to study discontinuation in ≥2% of patients was hallucination (10/502 [2%]; monotherapy n=1, adjunct therapy n=9).IX

About Parkinson's disease

Parkinson's disease is a chronic neurological disorder affecting an estimated 1.1 million people across Europe.[x] Symptoms of PD can be both motor and non-motor. Motor symptoms include slowness of movement (bradykinesia), tremor and rigidity. However, the disease can also cause non-motor symptoms such as sleep disturbances, depression, urinary problems and dementia.[xi] Collectively, these symptoms can also reduce quality of life.

About Requip-Modutab

Ropinirole (Requip), developed and marketed by GlaxoSmithKline, is the first and only approved once-daily non-ergot oral dopamine agonist for the treatment of PD. Ropinirole may be used alone (without levodopa) in the treatment of idiopathic Parkinson's disease. It may also be used as an adjunct to levodopa to help control wearing off effects and "on-off" fluctuations.

GlaxoSmithKline - one of the world's leading research-based pharmaceutical and healthcare companies - is committed to improving the quality of human life by enabling people to do more, feel better and live longer. For further information please visit http://www.gsk.com
*Requip-Modutab is also known as Requip LP, Requip XL, Requip Depot, Requip Prolib and Requip prolonged release tablets.

References

[i] Chaudhuri, KR et al. Ropinirole prolonged release improves nocturnal symptoms in patients with advanced Parkinson's disease with sleep disturbances. Abstract Mo-192 for the 13th International Congress of Parkinson's Disease and Movement Disorders; 2009 7-11 June; Paris, France

[ii] Happe S, Berger K. The association between caregiver burden and sleep disturbances in partners of patients with Parkinson's disease. Age Ageing 2002; 31(5): 349-54

[iii] Stocchi, F et al. editors. The Real Life, Real PD Survey, Pan-European Results and Recommendations for Change. 2008. Abstract available online http://www.epda.eu.com

[iv] Chaudhuri, KR. The Parkinson's disease sleep scale: a new instrument for assessing sleep and nocturnal disability in Parkinson's disease. J Neurol Neurosurg Psychiatry 2002;73: 629-635

[v] Barone et al. Treatment of nocturnal disturbances and excessive daytime sleepiness in Parkinson's disease. Neurology 2004;63 (Suppl 3):S35-S38

[vi] Tompson D, Vearer D. Steady-state pharmacokinetic properties of a 24-hour prolonged release formulation of ropinirole: results of two randomized studies in patients with Parkinson's disease. Clin Ther 2007; 29: 2654-2666

[vii] Růžička E et al.. A maintained reduction in "off" time is achieved with ropinirole prolonged release in patients with advanced Parkinson's disease not optimally controlled with L-dopa. Abstract We-195 for the 13th International Congress of Parkinson's Disease and Movement Disorders; 2009 7-11 June; Paris, France

[viii] Stocchi, F et al. Symptom control in patients with advanced Parkinson's disease: ropinirole prolonged release versus ropinirole immediate release. Abstract Th-183 for the 13th International Congress of Parkinson's Disease and Movement Disorders; 2009 7-11 June; Paris, France

[ix] Szczudlik A et al. Safety and tolerability of long-term treatment with ropinirole prolonged release in patients with early or advanced Parkinson's disease. Abstract Th-186 for the 13th International Congress of Parkinson's Disease and Movement Disorders; 2009 7-11 June; Paris, France

[x] EPDA Parkinson's Awareness Campaign 2008 (accessed 3rd June, 2009)

[xi] Chaudhuri KR et al. Non-motor symptoms of Parkinson's disease: diagnosis and management. Lancet Neurol 2006; 5 :235-45

Source
GlaxoSmithKline